Muscular System Disorders

MUSCULAR SYSTEM DISORDERS
Causes
The nerve damage associated with the disease was first thought to be caused by
metabolic changes such as endoneurial microvessel disease, which is the degeneration
Amyotrophy
of pericytes due to hyperglycemia, and the reproduction of basement membranes when
Amyotrophy is progressive wasting of muscle tissues. Muscle pain is also a symptom. It

can occur in middle-aged males with type 2 diabetes. It also occurs with motor neuron
disease.
plus the absence of the pericyte, which regulate capillary blood flow and phagocytosis of
Proximal diabetic neuropathy
ischemia.[7] Experimental treatments using immunosuppressive proteins have provided
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does occur in patients without diabetes the prevalence is much greater in the diabetic
Proximal diabetic neuropathy, also known as lumbosacral radioplexus

neurophagy, femoral neurophagy and diabetic amyotrophy, is a nerve disorder that
results as a complication of diabetes mellitus. It affects the thighs, hips, buttocks and
legs. Proximal diabetic neurophagy is a peripheral nerve disease (diabetic neuropathy)
characterized by painful muscle wasting and weakness. [1] Diabetic neuropathy is a
common complication of diabetes. It is defined as damage to the nerves that allow you to
feel the sensation pain. There are a number of ways that diabetes damages the nerves,
all of which seem to be related to increased blood sugar levels over a long period of time.
Proximal diabetic neuropathy is one of four types of diabetic neuropathy.[2]
indicating that although hyperglycemia does not directly cause the nerve damage it may
Proximal diabetic neuropathy can occur in type 2 and type 1 diabetes mellitus patients
however, it is most commonly found in type 2 diabetes patients.[3] Proximal neuropathy is
the second most common type of diabetic neuropathy and can be resolved with time and
treatment.
improperglucose levels in the muscles, resulting in extreme pain and muscle wasting.
Signs & Symptoms

Symptoms of proximal diabetic neuropathy depend on which nerves are affected. The
first symptom is usually pain in the buttocks, hips, thighs or legs. This pain most
commonly affects one side of the body and can either start gradually, seemingly minor at
first, or can come on all of a sudden. This is followed by intense weakness in
the proximal musclesof the lower limbs that can result in patients being unable to go from
a sitting to standing position without assistance. [3] This weakness begins unilaterally but
can also spreadbilaterally.[1]
Proximal diabetic neuropathy is often accompanied by polyneuropathy, a malfunction of
many peripheral nerves at the same time, and muscle fasciculation,
small, involuntarymuscle twitches or contractions that are visible under the skin. [1][5][6]
the pericytes are no longer regulating their cell cycle. The decreased size of the lumen
cellular debris, leads to ischemia. Nerve biopsies have shifted the view toward an
immune mechanism that causesMicro Vasculitis, which could eventually lead to
further corroborative evidence to the immune mechanism theory.[8] Although this disease
play a role
Diagnosis
Though very difficult to diagnose because of the similarity to other diseases, the causes
are often due to neurological lesions on the nerve endings that are created by
[9]
To definitively diagnose the condition, electrodiagnostic testing can be used. In
addition, needleelectromyography and nerve conduction testing are often used to

support the diagnostic and to rule out other possible conditions.
Treatment
Proper management of diabetes mellitus can prevent proximal diabetic
neuropathy from ever occurring.
Proximal diabetic neuropathy is very much reversible.[citation needed] This can be done by taking
various measures such as:
Controlling the blood sugar levels
Proper eating habits, medication, physical exercise, good mental health and
avoiding harmful habits like drinking, smoking etc. all form a part of the lifestyle to
control diabetes.
Physical therapy to restore the nerves in the legs is very useful, it brings back
feeling in the legs.
Medication helps reduce the pain involved in proximal diabetic neuropathy.

Most patients take oral medication that is prescribed by a doctor. Common types
includeantidepressants, opiates or opiate like drugs, and anticonvulsants.[3]
Length of treatment varies with the amount of nerve damage.[4]

The main treatment of diabetic amyotrophy is managing the individuals diabetes and
glycemic levels.[11] Once they have done these two tasks they will notice an improvement.
Receiving an IV of a corticosteroid or taking an immunosuppressant drug, will help to
relieve pain and start regaining strength.[12][13] While doing any of the treatment options
they should also be working with either a physical therapist or occupational therapist to
start gaining muscle strength back.
Treatment
There is no cure for MMA. Treatment consists of muscle strengthening exercises and
training in hand coordination. It has been proposed that that the changes in this disease
are from compression of the spinal cord in flexion due to forward shifting of the posterior
dural sac.[1] There have been treatements studies ranging from use of a cervical collar [2] to
anterior cervical fusion and posterior decomression. [3]
Prognosis
The symptoms of MMA usually progress slowly for one to two years before reaching a
plateau, and then remain stable for many years. Disability is generally slight. Rarely, the
weakness progresses to the opposite limb. There is also a slowly progressive variant of
MMA known as O'Sullivan-McLeod syndrome, which only affects the small muscles of
the hand and forearm and has a slowly progressive course.
Epidemiology
Monomelic amyotrophy
MMA occurs in males between the ages of 15 and 25. Onset and progression are slow.
MMA is seen most frequently in Asia, particularly in Japan and India; it is much less
common in North America.
Monomelic amyotrophy (MMA), also known as Hirayama disease, Sobue

disease, juvenile non-progressive amyotrophy and juvenile asymmetric segmental
spinal muscular atrophy (JASSMA) is an untreatable, focal motor neuron
disease that primarily affects young (1525 year old) males in India and Japan. MMA is
marked by insidious onset of muscular atrophy, which stabilizes at a plateau after two to
five years from which it neither improves nor worsens. There is no pain or sensory loss
associated with MMA. Unlike other lower motor neuron diseases, MMA is not believed to
be hereditary and fasciculations (involuntary muscle twitches) are rare.
EMG tests reveal loss of the nerve supply, or denervation, in the affected limb
without conduction block (nerve blockage restricted to a small segment of the nerve).
Increasedsweating, coldness and cyanosis have been reported for a few patients,
indicating involvement of the sympathetic nervous system.
While MMA will cause weakness and/or wasting in only one limb, EMG and NCV tests
often show signs of reinnervation in the unaffected limbs.
splints rarely causes serious health problems, while Anterior Compartment Syndrome
can lead to irreversible damage.
The true compartment syndrome arises due to increased pressure within the
unyielding anterior compartment of the leg. The pressure obstructs venous outflow,
which causes further swelling and increased pressure. The resultant ischemia leads
to necrosis (death of tissue) of the muscles and nerves. The process can begin with
swelling of the tibialis anterior, extensor hallucis longus, extensor digitorum longus,
and/or the peroneus tertius muscles in response to strong eccentric
contractions sufficient to produce postexercise soreness.
Symptoms
Diffuse tightness and tenderness over the entire belly of the tibialis anterior that does not
respond to elevation or pain medication can be early warning signs and suggestive of
Anterior Compartment Syndrome. Other common symptoms include excessive swelling
that causes the skin to become hot, stretched and glossy. Pain, paresthesias, and
tenderness in both the ischemic muscles and the region supplied by the deep common
Anterior compartment syndrome of the

lower leg
A compartment syndrome is an increased pressure within a muscular compartment [1] that
compromises the circulation to the muscles.
fibular nerve are exhibited by patients suffering from this condition. Sensitivity to passive
stretch and active contraction are common, and tend to increase the symptoms.
Diagnosis
Pathology
If these symptoms are observed/experienced it is important to contact a physician
A compartment space is anatomically determined by an unyielding fascial (and osseous)
specializing in sports medicine (MD/DO), a doctor of podiatric medicine (DPM), or other
enclosure of the muscles. The anterior compartment syndrome of the lower leg (often
qualified health care professional immediately so as to get the appropriate
referred to simply as anterior compartment syndrome), can affect any and all four
advice/treatment before serious damage occurs.
muscles of that compartment: tibialis anterior, extensor hallucis longus, extensor

digitorum longus, and peroneus tertius.
This term is often mistakenly used to describe various related/proximal conditions,
The 5 Ps of Anterior Compartment Syndrome:

1. Pain
including Anterior Shin Splints. It is important to distinguish between the two, as shin
2. Pallor
3. Paresthesia
4. Pulselessness
5. Paralysis (If not treated)
Cataplexy
Cataplexy is a sudden and transient episode of muscle weakness accompanied by

full conscious awareness, typically triggered by emotions such as laughing, crying,
terror, etc.[1] It is the cardinal symptom of narcolepsy with cataplexy affecting roughly
70% of people who have narcolepsy,[2] and is caused by an autoimmune destruction
of the neurotransmitter hypocretin, which regulates arousal and wakefulness.
Cataplexy without narcolepsy is rare and the cause is unknown.
Bimagrumab
Bimagrumab (BYM338) is a human monoclonal antibody developed by Novartis to treat

pathological muscle loss and weakness. On August 20, 2013 it was announced that
bimagrumab was granted breakthrough therapy designation for sporadic inclusion body
myositis (sIBM) by US Food and Drug Administration.
The term cataplexy originates from the Greek (kata, meaning "down"), and
(plxis, meaning "stroke").
Presentation[edit]
Cataplexy manifests itself as muscular weakness which may range from a barely
perceptible slackening of the facial muscles to complete muscle paralysis with postural
collapse.[3]Attacks are brief, most lasting from a few seconds to a couple of minutes, and
typically involve dropping of the jaw, neck weakness, and/or buckling of the knees,
similar to symptoms experienced by notable individuals, such as Ubong Ben-Ebong.
Even in a full-blown collapse, patients are usually able to avoid injury because they learn
to notice the feeling of the cataplectic attack approaching and the fall is usually slow and
progressive.[4] Speech may be slurred and vision may be impaired (double vision, inability
to focus), but hearing and awareness remain normal.
Cataplexy attacks are self-limiting and resolve without the need for medical intervention.
If the patient is reclining comfortably, he or she may transition into sleepiness,
hypnagogic hallucinations, or a sleep-onset REM period. While cataplexy worsens with
fatigue, it is different from narcoleptic sleep attacks and is usually, but not always
triggered by strong emotional reactions such as laughter, anger, surprise, awe,
and embarrassment, or by sudden physical effort, especially if the person is caught off
guard.[5] One well known example of this was the reaction of 1968 Olympic long
jump medalist Bob Beamon on understanding that he had broken the previous world
record by over 0.5 meters (2 feet).[6]Cataplectic attacks may also occur spontaneously
with no identifiable emotional trigger.[7]
Physiology
A survey of 100 cataplectic patients from the Stanford Sleep Disorders Clinic (age range
1424 years) reported that 93 percent of the attacks lasted less than two minutes, 6
Cataplexy is considered secondary when it is due to specific lesions in the brain that
percent reported events lasting up to five minutes, and 0.94 percent reported events
cause a depletion of the hypocretin neurotransmitter. Secondary cataplexy is associated
lasting longer than five minutes. There is a bimodal pattern of the age of onset of
with specific lesions located primarily in the lateral and posterior hypothalamus.
symptoms; either at 15 or 35 years. It has also been reported past the age of forty.
Cataplexy due to brainstem lesions is uncommon particularly when seen in isolation. The
Guilleminault et al. investigated 51 prepubertal children with narcolepsy; in 10 subjects (5
lesions include tumors of the brain or brainstem and arterio-venous malformations. Some
years and younger) cataplexy was the symptom first recognized. Cataplectic symptoms
of the tumors include astrocytoma, glioblastoma, glioma, and subependynoma. These
in general tend to decrease with age. A review of 100 patients with cataplexy at the
lesions can be visualized with brain imaging, however in their early stages they can be
Stanford Sleep Disorders Clinic (age range 1220 years) reported that 62 of these
missed. Other conditions in which cataplexy can be seen
patients stopped taking anti-cataplectic medications after 10 years. However, the general
include ischemic events, multiple sclerosis, head injury,paraneoplastic syndromes, and
decrease in cataplectic symptoms with aging may be reversed after the experience of a
infections such as encephalitis. Cataplexy may also occur transiently or permanently due
significant emotional upset, such as a loss of spouse in older subjects. [11]
to lesions of the hypothalamus that were caused by surgery, especially in difficult tumor
resections. These lesions or generalized processes disrupt the hypocretin neurons and
Hypocretin
their pathways. The neurological process behind the lesion impairs pathways controlling
the normal inhibition of muscle tone drop, consequently resulting in muscle atonia.[8]
The hypothalamus region of the brain regulates basic functions of hormone release,
emotional expression and sleep. A study in 2006 in "Tohoku Journal of Experimental
Theories for episodes
Medicine" concluded that the neurochemical hypocretin, which is regulated by the

hypothalamus, was significantly reduced in study participants with symptoms of
A phenomenon of REM sleep, muscular paralysis, occurs at an inappropriate time. This
cataplexy. Orexin, also known as Hypocretin, is a primary chemical important in
loss of tonus is caused by massive inhibition of motor neurons in the spinal cord. When
regulating sleep as well as states of arousal. Hypocretin deficiency is further associated
this happens during waking, the victim of a cataplectic attack loses control of his or her
with decreased levels of histamine and epinephrine, which are chemicals important in
muscles. As in REM sleep, the person continues to breathe and is able to control eye
promoting wakefulness, arousal and alertness.[12]
movements.
[9]
Studies
Treatment
Cataplexy is treated pharmacologically. There are no behavioral treatments for cataplexy.
A study of 40 cataplectic patients (age range 1323 years) reported that sagging of the
The cholinergic and noradrenergic neurotransmitter systems are targeted in the
jaw, inclined head, drooping of the shoulders, and transient buckling of the knees were
treatment of cataplexy. Despite its relation to narcolepsy, in most cases, cataplexy must
the most common presentations. Slurred speech may be present. However,
be treated differently and separate medication must be taken. For many years, cataplexy
diaphragmatic paralysis resulting in central apneas has not been reported. There is an
has been treated with tricyclic antidepressants such
isolated form that involves facial muscles exclusively. Cataplexy may rapidly reoccur
as imipramine, clomipramine or protriptyline. The main feature of tricyclics is their ability
repeatedly, giving birth to "status cataplecticus", and to the "limp man syndrome" as
to inhibit the reuptake of norepinephrine and serotonin at the nerve endings. [13] However
described by Stalh et al. "Status cataplecticus" is rare and can be extremely disabling to
these can have unpleasant side-effects and have been generally replaced by newer
the individual. Cataplexy also occurs more frequently in times of emotional stress and
drugs such as venlafaxine.
when patients are deprived of napping while sleepy.[10]
For cataplexy associated with narcolepsy, Xyrem (sodium oxybate) is often

recommended.[14]
Monoamine oxidase inhibitors may be used to manage both cataplexy and the REM
sleep-onset symptoms of sleep paralysis and hypnagogic hallucinations.[15]
Wise (2004) noted that people with narcolepsy will often try to avoid thoughts and
situations that they know are likely to evoke strong emotions because they know that
these emotions are likely to trigger cataplectic attacks.[16]
A newer class of antidepressants with selective serotonergic reuptake blocking
properties known as the selective serotonin reuptake
inhibitors fluoxetine, paroxetine, sertraline,citalopram has become popular for the
treatment of cataplexy. This class of drugs has an active metabolite with norepinephrine
reuptake blocking properties (such as nor-fluoxetine). Serotonin reuptake inhibitors
(SSRIs) have fewer side effects compared to the tricyclics and can be used in adults and
children. A side effect worth mentioning regarding tricyclic antidepressants and SSRIs is
the risk of development of REM behavior disorder (RBD) due to elimination of the normal
REM sleep atonia. These drugs are known to decrease stage REM sleep. They can also
decrease muscle atonia associated with REM sleep and consequently dissociate REM
sleep. As a consequence, the subject may act out his or her dreams and cause harm to
himself/herself or others.
Emerging therapies
Central core disease of muscle

Central core disease of muscle (CCD, CCO), also known as multicore
myopathy, multiminicore disease and congenital neuromuscular disease with
uniform type 1 bers (CNMDU1), is a rare myopathy disorder characterised by "early
onset of symptoms, mild proximal weakness, hyporeflexia or areflexia, normal serum
muscle enzyme levels, short duration of motor unitpotentials, uniform type 1 fibers, and
nonprogression".[1] The disease has a mild and non-progressive course and usually
manifests by weakness of hands.
Emerging therapies include Hypocretin Gene Therapy and Hypocretin Cell

Transplantation for narcolepsy-cataplexy.
The newest agent for the treatment of cataplexy is sodium oxybate (gamma-
Charley horse
hydroxybutyrate [GHB]), known commercially as Xyrem. Although its mechanism is

unknown, it reduces cataplectic attacks and other manifestations of REM sleep. GHB
increases slow wave sleep, decreases nighttime awakenings, and consolidates REM
sleep. Sodium oxybate is the only medication that will improve both cataplexy and
daytime sleepiness. Cataplectic symptoms are improved much faster. Because it can
cause daytime sleepiness, during this time, sodium oxybate should be taken
concomitantly with a stimulant.
Charley horse is a popular colloquial term in Canada and the United States for painful
spasms or cramps in the leg muscles, typically lasting anywhere from a few seconds to
about a day. It can also refer to a bruise on an arm or leg and a bruising of
thequadriceps muscle of the anterior or lateral thigh, or contusion of the femur, that
commonly results in a haematoma and sometimes several weeks of pain and disability.
In this latter sense, such an injury is known as dead leg.[1] In Australia it is also known as
acorked thigh or corky.[2] It often occurs in contact sports, such as football when an
athlete suffers a knee (blunt trauma) to the lateral quadriceps causing a haematoma or
temporary paresis and antalgic gait as a result of pain. Another term, jolly horse, is used
to describe simple painful muscle cramps in the leg or foot, especially those that follow
strenuous exercise.
typically present with ptosis (drooping eyelids). Other diseases like Graves'
The term can be used to refer to cramps in the foot muscles.
be ruled out.
These muscle cramps can have many possible causes directly resulting from high or low
pH or substrate concentrations in the blood, including hormonal imbalances, low levels
ofmagnesium, potassium or calcium, dehydration,[3] side effects of medication, or, more
seriously, diseases such as amyotrophic lateral sclerosis and neuropathy.[4] They are also
a common complaint during pregnancy.
Signs and symptoms
Treatment
period of 515 years.[1] The first presenting symptom of ptosis is often unnoticed by the
Relief is usually given by either massaging or stretching the foot, ankle or knee in the
opposite direction of the spasm.
Colloquial advice suggests that dietary deficiency of potassium, found richly in bananas
and many vegetables,[6] is a common cause of these spasms.
disease,myasthenia gravis and glioma that may cause an external ophthalmoplegia must
Of CPEO itself
CPEO is a slowly progressing disease. It may begin at any age and progresses over a
patient until the lids droop to the point of producing a visual field defect. Often, patients
will tilt the head backwards to adjust for the slowly progressing ptosis of the lids. In
addition, as the ptosis becomes complete, the patients will use the frontalis (forehead)
muscle to help elevate the lids. The ptosis is typically bilateral, but may be unilateral for a
period of months to years before the fellow lid becomes involved.
Ophthalmoplegia or the inability/difficulty to move the eye is usually symmetrical. As
such, double vision is sometimes a complaint of these patients. In fact, the progressive
ophthalmoplegia is often unnoticed till decreased ocular motility limits peripheral vision.
Often someone else will point out the ocular disturbance to the patient. Patients will
Chronic progressive external

ophthalmoplegia
Chronic progressive external ophthalmoplegia (CPEO), also known as progressive

external ophthalmoplegia (PEO), is a type of eye disorder characterized by slowly
progressive inability to move the eyes and eyebrows.[1] It is often the only feature
ofmitochondrial disease, in which case the term CPEO may be given as the diagnosis. In
other people suffering from mitochondrial disease, CPEO occurs as part of
a syndrome involving more than one part of the body, such as Kearns-Sayre syndrome.
Occasionally CPEO may be caused by conditions other than mitochondrial diseases.
Introduction
CPEO is a rare disease that may affect those of all ages, but typically manifests in the
young adult years. CPEO is the most common manifestation of mitochondrial myopathy,
occurring in an estimated two-thirds of all cases of mitochondrial myopathy. Patients
move their heads to adjust for the lost of peripheral vision caused by inability to abduct or
adduct the eye. All directions of gaze are affected, however, downward gaze appears to
be best spared. This is in contrast to Progressive Supranuclear Palsy (PSP) which
typically affects vertical gaze and spares horizontal gaze.
Occurring alongside CPEO

Weakness of extraocular muscle groups including, the orbicularis oculi muscle as well as
facial and limb muscles may be present in up to 25% of patients with CPEO. As a result
of the orbicularis oculi weakness, patients may suffer from exposure keratopathy
(damage to cornea) from the inability to close the eyes tightly. Frontalis muscle
weakness may exacerbate the ptotic lids with the inability to compensate for the ptosis.
Facial muscles may be involved which lead to atrophy of facial muscle groups producing
a thin, expressionless face with some having difficulty with chewing. Neck, shoulder and
extremity weakness with atrophy may affect some patients and can be mild or severe.
Mild visual impairment was seen in 95% of patients that were evaluated using the Visual
Whether a tissue is affected is correlated with the amount of oxidative demands in
Function Index (VF-14).[2]
relation to the amount of mtDNA deletion.
The ciliary muscles that control the lens shape and the iris muscles are often unaffected
In most cases, PEO occurs due to a sporadic deletion or duplication within the
by CPEO.
mitochondrial DNA.[5] However, transmission from the mother to the progeny appears
only in few cases. Both autosomal dominant and autosomal recessive inheritance can
Additional symptoms are variable, and may include exercise intolerance, cataracts,
occur, autosomal recessive inheritance being more severe. Dominant and recessive
hearing loss, sensory axonal neuropathy, ataxia, clinical depression, hypogonadism,
forms of PEO can be caused by genetic mutations in
andparkinsonism.
the ANT1, POLG, POLG2 and PEO1 genes.
Kearns-Sayre syndrome, is characterized by onset before 15 years of age of CPEO,
Diagnosis
heart block and pigmentary retinopathy.
[1]
Genetics
It is important to differentiate CPEO from other pathologies that may cause an

ophthalmoplegia. There are specific therapies used for these pathologies.
Mitochondrial DNA which is transmitted from the mother, encodes proteins that are
CPEO is diagnosed via muscle biopsy. On examination of muscle fibers stained
critical to the respiratory chain required to produce adenosine triphosphate (ATP).
with Gmri trichrome stain, one can see an accumulation of enlarged mitochondria.
Deletions or mutations to segments of mtDNA lead to defective function of oxidative
This produces a dark red staining of the muscle fibers given the name ragged red
phosphorylation. This may be made evident in highly oxidative tissues like skeletal
fibers. While ragged red fibers are seen in normal aging, amounts in excess of normal
muscle and heart tissue. However, extraocular muscles contain a volume of mitochondria
aging give a diagnosis of a mitochondrial myopathy.
that is several times greater than any other muscle group. As such, this results in the
preferential ocular symptoms of CPEO.
Polymerase Chain Reaction (PCR), from a sample of blood or muscle tissue can
determine a mutation of the mtDNA.
Multiple mtDNA abnormalities exist which cause CPEO. One mutation is located in a
conserved region of mitochondrial tRNA at nucleotide 3243 in which there is an A to G
Elevated acetylcholine receptor antibody level which is typically seen in myasthenia
nucleotide transition. This mutation is associated with both CPEO and Mitochondrial
gravis has been seen in certain patients of mitochondrial associated ophthalmoplegia. [7]
encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).[3]

It is important to have a dilated eye exam to determine if there is pigmentary retinopathy
A common deletion found in one-third of CPEO patients is a 4,977 base pair segment
that may signify Kearns-Sayre syndrome which is associated with cardiac abnormalities.
found between a 13 base pair repeat.

MRI may be helpful in the diagnosis, in one study volumes of medial rectus, lateral
The mtDNA that is affected maybe a single or multiple point deletion, with associated
rectus, and inferior rectus muscles in CPEO were not smaller than normal (in contrast to
nuclear DNA deletions. One study showed that mtDNA deletion seen in CPEO patients
the profound atrophy typical of neurogenic paralysis). Although volumes of the superior
also had an associated nuclear DNA deletion of the Twinkle gene which encodes specific
rectus muscle-levator complex and superior oblique were significantly reduced. [8]
mitochondrial protein; Twinkle.[4]
Treatment
There is currently no defined treatment to ameliorate the muscle weakness of CPEO.
Treatments used to treat other pathologies causing ophthalmoplegia has not been shown
to be effective.
Experimental treatment with tetracycline has been used to improve ocular motility in one
patient.[9] Coenzyme Q10 has also been used to treat this condition.[10] However, most
neuro-ophthalmologists do not ascribe to any treatment.
Contracture
Ptosis associated with CPEO may be corrected with surgery to raise the lids, however
due to weakness of the orbicularis oculi muscles, care must be taken not to raise the lids
in excess causing an inability to close the lids. This results in an exposure keratopathy.
Therefore, rarely should lid surgery be performed and only by a neuro-ophthalmologist
familiar with the disease.
The most common strabismus findings is large angle exotropias which can be treated by
maximal bilateral eye surgery, but due to the progressive nature of the disease,
strabismus may recur.[11] Those that have diplopia as a result of asymmetric
ophthalmoplegia maybe corrected with prisms or with surgery to create a better
alignment of the eyes.
A muscle contracture is a permanent shortening of a muscle[1] or joint.[2] It is usually

in response to prolonged hypertonic spasticityin a concentrated muscle area, such
as is seen in the tightest muscles of people with conditions like spastic cerebral
palsy.
Contractures are essentially muscles or tendons that have remained too tight for too
long, thus becoming shorter. Once they occur, it is often argued that they cannot be
stretched or exercised away (they must be released with orthopedic surgery). Most
of the physical therapy, occupational therapy, and other exercise regimens targeted
towards people with spasticity focuses on trying to prevent contractures from
happening in the first place. However, research on sustained traction of connective
tissue in approaches such as adaptive yoga has demonstrated that contracture can
be reduced,[3] at the same time that tendency toward spasticity is addressed.
Contractures can also be due to ischemia, as in Volkmann's contracture.
Excessive matrix metalloproteinase and myofibroblast accumulation in the wound
margins can result in contracture.
Cramp
A cramp is a sudden, severe, and involuntary muscle contraction or over-shortening;

while generally temporary and non-damaging, they can cause mild-to-excruciating pain,
and a paralysis-like immobility of the affected muscle(s). Onset is usually sudden, and it
resolves on its own over a period of several seconds, minutes, or hours. Cramps may
occur in a skeletal muscle or smooth muscle. Skeletal muscle cramps may be caused by
any combination of muscle fatigue, a lack of electrolytes (e.g., low sodium, low
potassium, or low magnesium)[ Cramps of smooth muscle may be due

to menstruation or gastroenteritis.
[4]
Hypoglycemia and reactive hypoglycemia are associated with excess insulin (or
insufficient glucagon), and avoidance of low blood glucose concentration may help to
avoid cramps.
Smooth muscle cramps

Smooth muscle contractions may be symptomatic of endometriosis or other health
problems. Menstrual cramps may also occur both before and during a menstrual cycle.
Skeletal muscle cramps

See also: Exercise-associated muscle cramps
Skeletal muscles can be voluntarily controlled, under normal circumstances. Skeletal
muscles that cramp the most often are the calves, thighs, and arches of the foot, and are
sometimes called a "Charley horse" or a "corkie". Such cramping is associated with
strenuous physical activity and can be intensely painful; however, they can even occur
while inactive/relaxed. Around 40% of people who experience skeletal cramps are likely
Differential diagnosis
to endure extreme muscle pain, and may be unable to use the entire limb that contains
the "locked-up" muscle group. It may take up to seven days for the muscle to return to a
Causes of cramping include hyperflexion, hypoxia, exposure to large changes in

[1]
pain-free state.
temperature, dehydration, or low blood salt. Muscle cramps may also be a symptom or
complication
Nocturnal leg cramps
of pregnancy, kidney disease, thyroid disease, hypokalemia, hypomagnesemia or hypoc
See also: Charley horse
alcemia (as conditions), restless-leg syndrome, varicose veins,[2] and multiple sclerosis.[3]
Nocturnal leg cramps are involuntary muscle contractions that occur in
Electrolyte disturbance may cause cramping and muscle tetany,
the calves, soles of the feet, or other muscles in the body during the night or (less
particularly hypokalaemia and hypocalcaemia. This disturbance arises as the body loses
commonly) while resting.
large amounts ofinterstitial fluid through sweat. This interstitial fluid comprises mostly
water and salt (sodium chloride). The loss of osmotically active particles outside
of muscle cells leads to a disturbance of the osmotic balance and therefore shrinking of
muscle cells, as these contain more osmotically active particles. This causes the calcium
pump between the musclesarcoplasm and sarcoplasmic reticulum to short circuit; the
The duration of nocturnal leg cramps is variable with cramps lasting anywhere from a few
seconds to several minutes. Muscle soreness may remain after the cramp itself ends.
These cramps are more common in older people.[5] They happen quite frequently in
teenagers and in some people while exercising at night. The precise cause of these
calcium ions remain bound to the troponin, continuing muscle contraction.
cramps is unclear. Potential contributing factors include dehydration, low levels of certain
As early as 1965, researchers observed that leg cramps and restless-leg syndrome
muscles attendant in prolonged sitting or lying down. Nocturnal leg cramps (almost
result from excess insulin, sometimes called hyperinsulinemia.
exclusively calf cramps) are considered 'normal' during the late stages of pregnancy.
minerals (magnesium, potassium, calcium, and sodium), and reduced blood flow through
They can, however, vary in intensity from mild to extremely painful.
A lactic acid buildup around muscles can trigger cramps; however, these happen during
Pathophysiology
anaerobic respiration when a person is exercising or engaging in an activity where the
Main article: Muscle contraction
heart beat speeds up. Medical conditions associated with leg cramps are cardiovascular
Skeletal muscles work as antagonistic pairs. Contracting one skeletal muscle requires
disease, cirrhosis, pregnancy, and lumbar canal stenosis.
the relaxation of the opposing muscle in the pair. Cramps can occur when muscles are
Various medications may cause nocturnal leg cramps:[6]
unable to relax properly due to myosin fibers not fully detaching from actin filaments. In
skeletal muscle, adenosine triphosphate (ATP) must attach to the myosin heads for them
Diuretics, especially potassium sparing
Long acting adrenergic beta-agonists (LABAs)
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (HMG-CoA inhibitors
to disassociate from the actin and allow relaxation the absence of ATP in sufficient
quantities means that the myosin heads remains attached to actin. An attempt to force a
muscle cramped in this way to extend (by contracting the opposing muscle) can tear
muscle tissue and worsen the pain. The muscle must be allowed to recover
(resynthesize ATP), before the myosin fibres can detach and allow the muscle to relax.
or statins)
Treatment
Besides being painful, a nocturnal leg cramp can cause much distress and anxiety.[7]
Stretching, massage and drinking plenty of fluid, such as water, may be helpful in treating
Gentle stretching and massage, putting some pressure on the affected leg by walking or
simple muscle cramps.[13] With exertional heat cramps due to electrolyte
standing, or taking a warm bath or shower may help to end the cramp. If the cramp is in
abnormalities(primarily sodium loss and not calcium, magnesium, and potassium)
the calf muscle, pulling the big toe gently backwards will stretch the muscle and, in some
appropriate fluids and sufficient salt improves symptoms.[14]
[8]
cases, cause almost immediate relief.
Medication
Iatrogenic causes
Quinine is likely to be effective, however, due to side effects its use should only be
Statins may sometimes cause myalgia and cramps among other possible side effects.
considered if other treatments have failed.[15] Vitamin B complex, naftidrofuryl, lidocaine,
Raloxifene (Evista) is a medication associated with a high incidence of leg cramps.
and calcium channel blockers may be effective for muscle cramps.[15] Research has also
Additional factors, which increase the probability for these side effects, are physical
shown that pickle juice can be an effective remedy based on its high sodium and
exercise, age, female gender, history of cramps, and hypothyroidism. Up to 80% of
electrolyte content.[16] Cyclobenzaprine (Flexoril) has proven effective in preventing
athletes using statins suffer significant adverse muscular effects, including cramps; the
muscle cramps, although data suggests that effectiveness decreases when taken for
rate appears to be approximately 1025% in a typical statin-using population. [10][11] In
more than several weeks.
[9]
some cases, adverse effects disappear after switching to a different statin; however, they
should not be ignored if they persist, as they can, in rare cases, develop into more
Prevention
serious problems. Coenzyme Q10 supplementation can be helpful to avoid some statinrelated adverse effects, but currently there is not enough evidence to prove the
Adequate conditioning, stretching, mental preparation, and adequate fluid/electrolyte
effectiveness in avoiding myopathy or myalgia.
balance are likely helpful in preventing muscle cramps.
Physiology
There are two sphincters in the oesophagus. They are normally contracted and they
relax when you swallow so that food can pass through them going to the stomach. They
then squeeze closed again to prevent regurgitation of the stomach contents. If this
normal contraction becomes a spasm, these symptoms start. [1]
Symptoms
Sensation of a 'lump' in the back of the throat
Throat feels swollen
Discomfort - Lump can often feel quite big and pain is occasional
Symptoms normally worse in the evening
Stress aggravates the symptoms
Saliva is difficult to swallow, yet food is easy to swallow - eating, in fact, often
makes the tightness go away for a time
'Lump' sensation comes and goes from day to day
Symptoms can persist for very long periods, often several months.
The symptoms can be mimicked by pushing on the cartilage in the neck, just
below the Adam's apple
Cricopharyngeal spasm
Cricopharyngeal spasms occur in the cricopharyngeus muscle of the pharynx. These
spasms are frequently misunderstood by the patient to be cancer due to the 'lump in the
throat' feeling (Globus pharyngis) that is symptomatic of this syndrome. In practice, real
lumps in the throat, such as a cancer, are generally not felt until they impede ingestion of
foodThis is one of the reasons that a cancer can get so big before it is discovered.
However, a cricopharyngeal spasm is a harmless, if uncomfortable,
Causes
Stress and Anxiety. Other causes are not yet clear. In some cases, eating certain foods
may bring on acute spasms, in susceptible individuals. Peanuts, pumpkin seeds and
other nuts may trigger these spasms.
Cures
No real 'cure' exists, the sufferer must simply wait for it to fix itself. A number of
treatments will make it much less noticeable;
Muscle Relaxants
Lorazepam (Ativan), diazepam (Valium) and other benzodiazepines relax

the smooth muscle in the throat, slowing or halting contractions. In some people,
benzodiazepines may have addictive properties.
Diastasis recti
Diastasis recti (also known as abdominal separation) is commonly defined as a gap of

roughly 2.7 cm or greater between the two sides of the rectus abdominis muscle.[1] This
condition has no associated morbidity or mortality.[2]
The distance between the right and left rectus abdominis muscles is created by the
stretching of the linea alba, a connective collagen sheath created by the aponeurosis
insertions of the transverse abdominis, internal oblique, and external oblique. [3]
Diastasis of this muscle occurs principally in two populations: newborns and pregnant
women. It is also known to occur in men.
Reduce Stress
High stress levels make these spasms more noticeable
It is advisable to take note of when your symptoms are at their worst
Warm Fluids
In the newborn, the rectus abdominis is not fully developed and may not be
sealed together at midline. Diastasis recti is more common
in premature and black newborns.
In pregnant or postpartum women, the condition is caused by the stretching of

the rectus abdominis by the growing uterus. It is more common
in multiparous women due to repeated episodes of stretching. When the defect
Hot fluids may be helpful for some people cricopharyngeal spasm (or
occurs during pregnancy, the uterus can sometimes be seen bulging through the
other esophageal disorders)
abdominal wall beneath the skin.
Women are more susceptible to develop diastasis recti when over the age of 35,
high birth weight of child, multiple birth pregnancy, and multiple pregnancies.
Additional causes can be attributed to excessive abdominal exercises after the first
trimester of pregnancy.
Presentation
A diastasis recti may appear as a ridge running down the midline of the abdomen,
anywhere from the xiphoid process to the umbilicus. It becomes more prominent with
straining and may disappear when the abdominal muscles are relaxed. The medial
borders of the right and left halves of the muscle may be palpated during contraction of
the rectus abdominis.[5] The condition can be diagnosed by physical exam, and must be
differentiated from an epigastric hernia or incisional hernia, if the patient has had
is insufficient evidence to recommend that exercise may help to prevent or reduce
abdominal surgery.[2] Hernias may be ruled out using ultrasound.
DRAM.[1]
In infants, they typically result from a minor defect of the linea alba between the rectus
Exercises
abdominis muscles. This allows tissue from inside the abdomen to herniate anteriorly. On
infants, this may manifest as an apparent 'bubble' under the skin of the belly between
Nevertheless, the following exercises are often recommended to help build abdominal
the umbilicus and xiphisternum (bottom of the breastbone).
strength, which may or may not help reduce the size of diastasis recti[8]
Examination is performed with the subject lying on their back, knees bent at 90 with feet
Core contraction - In a seated position, place both hands on abdominal
flat, head slightly lifted placing chin on chest. With muscles tense, examiners then place
muscles. Take small controlled breaths. Slowly contract the abdominal muscles,
fingers in the ridge that is presented. Measurement of the width of separation is
pulling them straight back towards the spine. Hold the contraction for 30 seconds,
determined by the number of fingertips that can fit within the space between the left and
while maintaining the controlled breathing. Complete 10 repetitions.[8]
rightrectus abdominis muscles. Separation consisting of a width of 2 fingertips

(approximately 1 1/2 centimeters) or more is the determining factor for diagnosing
diastasis recti.
[6]
button, and the other below the belly button. With controlled breaths, with a mid-way
starting point, pull the abdominals back toward the spine, hold for 2 seconds and
Treatment
No treatment is necessary for women while they are still pregnant. In children,
complications include development of an umbilical or ventral hernia, which is rare and
Seated squeeze - Again in a seated position, place one hand above the belly
return to the mid-way point. Complete 100 repetitions.[8]
Head lift - In a lying down position, knees bent at 90 angle, feet flat, slowly lift
the head, chin toward your chest, (concentrate on isolation of the abdominals to
can be corrected with surgery.[7]
prevent hip-flexors from being engaged),[6] slowly contract abdominals toward floor,
Alerting a medical professional is important when an infant displays signs of vomiting,
hold for two seconds, lower head to starting position for 2 seconds. Complete 10
redness or pain in the abdominal area.
repetitions.[8]
Typically the separation of the abdominal muscles will lessen within the first 8 weeks
after childbirth, however the connective tissue remains stretched for many postpartum
length away from wall, place hands flat against the wall, contract abdominal muscles
women. The weakening of the abdominal muscles and the reduced force transmission
toward spine, lean body towards wall, with elbows bent downward close to body, pull
from the stretched linea alba may also make it difficult to lift objects, and cause lower
abdominal muscles in further, with controlled breathing. Release muscles as you
back pain. Additional complications can manifest in weakened pelvic alignment and
push back to starting position. Complete 20 repetitions.[8]
altered posture.[6]
Physiotherapy
Upright push-up - A standup pushup against the wall, with feet together arms-
Squat against the wall - Also known as a seated squat, stand with back against
the wall, feet out in front of body, slowly lower body to a seated position so knees are
A Systematic Review of the evidence found that exercise may or may not reduce the size
of the gap in pregnant or postpartum women. The authors looked at 8 studies totaling
336 women and concluded, Due to the low number and quality of included articles, there
bent at a 90 angle, contracting abs toward spine as you raise body back to standing
position. Optionally, this exercise can also be done using an exercise ball placed
against the wall and your lower back. Complete 20 Repetitions.[8]
Squat with squeeze - A variation to the "Squat against the wall" is to place a
small resistance ball between the knees, and squeeze the ball as you lower your
body to the seated position. Complete 20 repetitions. [8]
It is also noted that incorrect exercises, including crunches can actually increase the
distasis recti separation. All corrective exercises should be in the form of pulling in of the
abdominal muscles rather than a pushing of them outwards. Consultation of a
professional physiotherapist is recommended for correct exercise routines. [8]
In addition to the above exercises, the Touro College study concluded the "quadruped"
position yielded the most effective results.[6] A quadruped position is defined as "a human
whose body weight is supported by both arms as well as both legs".[9] In this position, the
subject would start with a flat back, then slowly tilt the head down, and arch the back,
contracting the abdominal muscles towards the spine, holding this position for 5 seconds,
then releasing back to starting position. Complete 2 sets of 10 repetitions. [6]
Surgical
In extreme cases, diastasis recti is corrected during the cosmetic surgery procedure
known as an abdominoplasty by creating a plication or folding of the linea alba and
suturing together. This creates a tighter abdominal wall.
In adult females, a laparoscopic Venetian blind technique can be used for plication of the
recti.
Distal spinal muscular atrophy type 2

Distal spinal muscular atrophy type 2 (DSMA2), also known as Jerash type distal
hereditary motor neuropathy (HMN-J) is a childhood-onset genetic disorder
characterised by progressive muscle wasting affecting lower and subsequently upper
limbs. The disorder has been described in Arab inhabitants of Jerash region in Jordan.[1][2]
The condition is linked to a genetic mutation in the locus 9p21.1p12 (chromosome 9)
and is likely inherited in an autosomal recessive manner.
Exercise therapy for idiopathic

inflammatory myopathies
Weight bearing activity

The results produced by aerobic activity were repeated in 1999
[7]
where for 12 weeks,
weight-bearing exercise was added for patients not exhibiting marked physical incapacity
as measured by the Functional Index in Myositis. [2] (see Functional Assessment
Although they vary in particulars, polymyositis, dermatomyositis and inclusion body

myositis are idiopathic inflammatory myopathies (IIM)[1] primarily characterized by
chronicinflammation of human skeletal muscle tissue[1] that ultimately causes
the necrosis of muscle cells. This degeneration leads to muscle tissue wasting,
weakness and fatigue among other serious effects. Until recently, exercise has been
avoided as a type of therapy, and even forbidden due to the risk of triggering or
amplifying inflammation. However, several studies have been conducted to test this
assumption and have shown that aerobic exercise as well as resistance training can
maintain and even improve quality of life for IIM-affected individuals without
increased inflammatory response.
section). Confirmed by MRI and muscle biopsy, both the 1998 and 1999 studies showed
that there were no significant changes in levels of creatine kinase and aldolase, and no
increase in muscle inflammation. In 2001, 22 patients were placed on a three week
physical therapy and exercise program, and found that creatine kinase levels actually
dropped in 20 of the patients.[8]
The longest study to date was a six-month exercise program demonstrating a significant
improvement in exercise capacity, VO2, isokinetic strength, and the ability to perform
daily tasks compared to controls.[6]
Modes of exercise therapy: trials
Stretching and range of motion activity

With the main goals of treatment being improved functionality and quality of life, exercise
programs should focus on functional exercises (e.g. walking, walking up/down stairs,
Chest expansion and thoracic extension exercises may offer preventive support to those
sit-to-stand), when applicable. Performing functional exercises increases (a) the
at risk of restrictive lung disease through the effects of IIM, and patients with inclusion
efficiency of the exercise program and (b) the likelihood the improvements will be
body myositis may also be able to prevent contracture and extend functional daily
transferred to activities of daily living.
activities through stretching and range of motion exercises [9]
[3]
Isometric activity
Monitoring
In 1993, isometric exercise training was applied for four weeks resulting in isometric peak
It is important to recognize that all described exercise programs were conducted by
power at 60% of maximal voluntary contraction.[4] The increase in isometric power was
physicians or physiotherapists during the stable phase of the disease (except Painelli [2]).
later shown to have no significant effect on serum creatine kinase (CK) after two weeks
Patients were monitored closely for indicators of deleterious effects, such as increases in
of strength training.[5]
serum creatine kinase, inflammation or weakness. Monitoring of this kind can only be
done in conjunction with a medical team who is aware of the risks posed by
Aerobic activity
increased inflammatory response in patients with IIM.
A six-week training program in 1998 that included 30 minutes of aerobic activity three
Future research
times per week set at 60% maximum heart rate (predicted by age) resulted in
increased VO2max (i.e. maximal oxygen consumption or aerobic capacity), diminished
The pathophysiology of IIMs is not well understood. Muscle weakness can be caused by
pain, reduced muscle impairment, and improved quality of life.
a single or combined effect on muscle tissue by inflammation, inflammatory infiltrates,
[6]
muscle atrophy, metabolic abnormalities that indicate disordered energy metabolism,
[1]
and possibly neuropathy,[10] among others. Therefore physical exercise has the potential
Neuromuscular control
to cause harm.
The second hypothesis is altered neuromuscular control. In this hypothesis, it is
However, the results of these exercise studies, at minimum, show that exercise can
suggested that cramping is due to altered neuromuscular activity. The proposed
attenuate muscle damage due to disease, inactivity and steroid use. They reflect the
underlying cause of the altered neuromuscular control is due to fatigue.[2] There are
benefit of exercise through the strengthening of complement (non-diseased) muscles,
several disturbances, at various levels of the central and peripheral nervous system, and
and should encourage further studies to confirm whether diseased muscle may
the skeletal muscle that contribute to cramping. These disturbances can be described by
experience regeneration. The definition of improvement must be established, [1] and
a series of several key events. First and foremost, repetitive muscle exercise can lead to
reproducible longitudinal studies must be conducted to determine the efficacy of exercise
the development of fatigue due to one or more of the following: inadequate conditioning,
as therapy for IIM.
hot and or humid environments, increased intensity, increased duration, and decreased
[2]
supply of energy. Muscle fatigue itself causes increased excitatory afferent activity within
the muscle spindles and decreased inhibitory afferent activity within the Golgi tendon.
The coupling of these events leads to altered neuromuscular control from the spinal cord.
Exercise-associated muscle cramps

Exercise-associated muscle cramps (EAMC) are defined as cramping (painful muscle

spasms) during or immediately following exercise.[1][2][3] Muscle cramps during exercise are
very common, even in elite athletes. EAMC are a common condition that occurs during
or after exercise, often during endurance events such as a triathlon or marathon. [1]
[3]
Although EAMC are extremely common among athletes, the cause is still not fully
understood because muscle cramping can occur as a result of many underlying
conditions. Elite athletes experience cramping due to paces at higher intensities. [2][3] The
cause of exercise-associated muscle cramps is hypothesized to be due to altered
neuromuscular control,dehydration, or electrolyte depletion.
A cascade of events follow the altered neuromuscular control; this includes increased
alpha-motor neuronactivity in the spinal cord, which overloads the lower motor neurons,
and increased muscle cell membrane activity.[2] Thus, the resultant of this cascade is a
muscle cramp.
Treatment and prevention

Medication has not been found to help reduce or prevent muscle cramping. To prevent or
treat, athletes are recommended to stretch, stop movement and rest, massaging the
area that is cramping, or drink fluids. Stretching helps to calm down spindles by
lengthening the muscle fibers and increase firing duration to slow down the firing rate of
the muscle.[1] Recommended fluids during cramping are water or fluids that are high in
Electrolyte depletion and dehydration theory

It is widely believed that excessive sweating due to strenuous exercise can lead to
muscle cramps. Deficiency of sodium and other electrolytes may lead to contracted
interstitial fluid compartments, which may exacerbate the muscle cramping. According to
this theory, the increased blood plasma osmolality from sweating sodium losses causes
a fluid shift from the interstitial space to the intervascular space, which causes the
interstitial fluid compartment to deform and contributes to muscle hyperexcitability and
risk of spontaneous muscle activity.[1][2]
electrolytes to replenish the system with sodium.
of calcium into the muscle fibers increasing calcium permeability. Calcium ions build up
in the mitochondria, impairing cellular respiration.[7] The mitochondria are unable to
produce enough ATP to power the cell properly. Reduction in ATP production impairs the
cells ability to extract calcium from the muscle cell.
The ion imbalance causes calcium -dependent enzymes to activate which break down
Exertional rhabdomyolysis
muscle proteins even further.[8] High concentrations of calcium cause the muscle to
contract in the muscle cells activate the which inhibits the muscles ability to relax due to
increased muscle activation.
Exertional rhabdomyolysis (ER) sometimes called exercise-induced

rhabdomyolysis is the breakdown of muscle from extreme physical exertion. It is one
of many types of rhabdomyolysis that can occur and because of this the
exact prevalence and incidence are unclear. Awareness of the issue is low among both
athletes and coaches, raising awareness of the disease and its risk factors can help
reduce incidence.
Cause
The increase of sustained muscle contraction leads to oxygen and ATP depletion with
prolonged exposure to calcium. The muscle cell membrane pump may become damaged
allowing free form myoglobin to leak into the bloodstream.
Physiology
ER is more likely to occur when strenuous exercise is performed under high
Rhabdomyolsis causes the myosin and actin to degenerate into smaller proteins that
temperatures and humidity. Poor hydration levels before, during, and after strenuous
travel into the circulatory system. The body reacts by increasing intracellular swelling to
bouts ofexercise have also been reported to lead to ER. This condition and its signs
the injured tissue to send repair cells to the area. This allows creatine
and symptoms are not well known amongst the sport and fitness community and
kinase and myoglobin to be flushed from the tissue where it travels in the blood until
[1]
[2]
because of this it is believed that the incidence is greater but highly underreported.
[3]
reaching the kidneys.[9] In addition to the proteins released large quantities of ions such
as intracellular potassium, sodium, and chloride find their way into the circulatory system.
Risks that lead to ER include exercise in hot and humid conditions, improper hydration,
Intracellular potassium ion has deleterious effects on the heart's ability to generate action
inadequate recovery between bouts of exercise, intense physical training, and
potentials leading to cardiac arrhythmias.[10] Consequently, this can affect peripheral and
inadequate fitness levels for beginning high intensity workouts. Dehydration is one of
central perfusion that can affect all major organ systems in the body.
[4]
the biggest factors that can give almost immediate feedback from the body by producing
very dark colored urine.[5]
When the protein reaches the kidneys it causes a strain on the anatomical structures
reducing its effectiveness as a filter for the body. The protein acts like a dam as it forms
Mechanism of injury
into tight aggregates when it enters the renal tubules.[11] In addition, the increased
Anatomy
intracellular calciumhas greater time to bind due to the blockage allowing for renal calculi
to form.[12] As a result this causes urine output to decrease allowing for the uric acid to
Exertional rhabdomyolysis results from damage to the intercellular proteins inside
build up inside the organ. The increased acid concentration allows the iron from the
the sarcolemma. Myosin and actin break down in the sarcomeres when ATP is no longer
aggregate protein to be released into the surrounding renal tissue. [13] Iron then strips
available due to injury to the sarcoplasmic reticulum. Damage to the sarcolemma and
away molecular bonds of the surrounding tissue which eventually will lead to renal failure
[6]
sarcoplasmic reticulum from direct trauma or high force production causes a high influx
Mechanical consideration
Diagnosis
Muscle degeneration from rhabdomyolysis destroys the myosin and actin filaments in the
Exertional rhabdomyolysis, the exercise-induced muscle breakdown that results in
affected tissue. This initiates the body's natural reaction to increase perfusion to the area
muscle pain/soreness, is commonly diagnosed using the urine myoglobin test
allowing for an influx of specialized cells to repair the injury. However, the swelling
accompanied by high levels of creatine kinase (CK). Myoglobin is the protein released
increases the intracellular pressure beyond normal limits. As the pressure builds in the
into the bloodstream when skeletal muscle is broken down. The urine test simply
muscle tissue, the surrounding tissue is crushed against underlying tissue and bone.
examines whether myoglobin is present or absent. When results are positive
[14]
This is known as compartment syndrome which leads to greater death of the
the urine normally obtains a dark, brown color followed by serum CK level evaluation to
surrounding muscle tissue around the injury.[15] As the muscle dies this will cause pain to
determine the severity of muscle damage. Elevated levels of serum CK greater than
radiate from the affected area into the compartmentalized tissue. A loss of range of
5,000 U/L that are not caused by myocardial infarction, brain injury, or disease generally
motion from swelling will also be seen in the affected limb. Along with muscle strength
indicate serious muscle damage confirming diagnosis of ER.[21]
weakness associated with the muscles involved from loss of filament interaction.
Treatment
Dehydration is a common risk factor for exertional rhabdomyolsis because it causes a

reduction of plasma volume during exertion. This leads to a reduction of blood flow
After ER is diagnosed, treatment is applied to 1) avoid renal dysfunction and 2)
through the vascular system which inhibits blood vessel constriction. [16]
alleviate symptoms. This should be followed by

recommended rehabilitation program, exercise prescription (ExRx). Treatment involves
Prevention
extensive hydration normally done through IV fluid replacement with administration of

normal saline until CK levels reduce to a maximum of 1,000 U/L.[22] Proper treatment will
Military data suggestlowering the risk of exertional rhabdomyolysis can be obtained by
ensure hydration and normalize muscle discomfort (pain), flu-like symptoms, CK levels,
engaging in prolonged lower intensityexercise, as opposed to high intensity exercise over
and myoglobin levels for patient to begin ExRx.
a shorter time period. In all athletic programs, three features should be present; (1)
emphasizing prolonged lower intensity exercise, as opposed to repetitive max intensity
Although sufficient evidence is currently lacking, supplementation with a combination of
exercises. (2) Adequate rest periods and a highcarbohydrate diet
sodium bicarbonate and mannitol is commonly utilized to prevent renal failure in
replenish glycogen stores. (3) Proper hydration will enhance renal clearance of
rhabdomyolysis patients. Sodium bicarbonate alkalizes urine to stop myoglobin from
myoglobin.[17] Also, exercise in above average temperature and humidity can increase
precipitating in renal tubules. Mannitol has several effects including, vasodilatation of
risk for exertional rhabdomyolysis.[18] Exertional rhabdomyolysis can be avoided by
renal vasculature, osmotic diuresis, and free radical scavenging. [23]
gradually increasing intensity during new exercise regimens, properly

hydrating, acclimatization, and avoidance of diuretics during times of strenuous activity.[19]
Recovery
Supplementation
Before initiating any form of physical activity the individual must demonstrate a normal
level of functioning with all previous symptoms absent. Physical activity should be
Sodium bicarbonate supplementation can reduce myoglobin, and prevent exertional
supervised by a health care professional in case of a reoccurrence. However, in some
rhabdomyolysis.
low risk individuals supervision by a medical professional is not required as long as
[20]
individual follows up with weekly check ups.[24] Proper hydration prior to performing
physical activity and performing exercise in cool, dry environments may reduce the
chances of developing a reoccurring episode of ER.[25] Lastly, it is imperative for urine and
blood values to be monitored along with careful observation for redevelopment of any
leads to the formation of FOP bones usually occurs before the age of 10. The bone
signs or symptoms.
growth progresses from the top downward, just as bones grow in fetuses. A child with
FOP will typically develop bones starting at the neck, then on the shoulders, arms, chest
The recovery program focuses on progressively conditioning/reconditioning the individual
area and finally on the feet.
and improving functional mobility. However, special considerations prior to participating in

rehabilitation program include the individuals 1) extent of muscle injury, if any 2) level of
Specifically, FOP involvement is typically seen first in the dorsal, axial, cranial and
fitness before incident and 3) weight training experience.[26] These special considerations
proximal regions of the body. Later the disease progresses in the ventral, appendicular,
collectively are a form of assessing the individuals capacity to perform physical activity,
caudal and distal regions of the body.[2] However, it does not necessarily occur in this
which is ultimately used to specify the ExRx design.
order due to injury-caused flare-ups. Often, the tumor-like lumps that characterize the
Costs
Actual cost for this condition is unknown and also dependent of the level of the condition.
In some cases ER can lead to acute renal failure and bring medical costs up due to the
need for hemodialysis for recovery/treatment.
disease appear suddenly. This condition causes loss of mobility to affected joints,
including inability to fully open the mouth limiting speech and eating. Extra bone
formation around the rib cage restricts the expansion of lungs and diaphragm causing
breathing complications.
Since the disease is so rare, the symptoms are often misdiagnosed as cancer or fibrosis.
This leads physicians to order biopsies, which can actually exacerbate the growth of
these lumps. However, those born with FOP tend to have malformed toes or thumbs
which help distinguish this disorder from other skeletal problems.[3]
Causes
Fibrodysplasia ossificans progressiva
FOP is caused by an autosomal dominant allele on chromosome 2q23-24.[4] The allele

has variable expressivity, but complete penetrance. Most cases are caused by
spontaneous mutation in the gametes; most people with FOP cannot or choose not to
have children. A similar but less catastrophic disease is fibrous dysplasia, which is
caused by a post-zygotic mutation.
Fibrodysplasia ossificans progressiva (FOP), sometimes referred to as Stone Man

Syndrome, is an extremely rare disease of the connective tissue. A mutation of the
A mutation in the gene ACVR1 (also known as activin-like kinase 2 [ALK-2]) is
body's repair mechanism causes fibrous tissue (including muscle, tendon, and ligament)
responsible for the disease.[5] ACVR1 encodes activin receptor type-1, a BMP type-1
to be ossified spontaneously or when damaged. In many cases, injuries can cause joints
receptor. The mutation causes substitution of codon 206 from arginine to histidine in the
to become permanently frozen in place. Surgical removal of the extra bone growths has
ACVR1 protein. This substitution causes abnormal activation of ACVR1, leading to the
been shown to cause the body to "repair" the affected area with more bone.
transformation of connective tissue and muscle tissue into a secondary skeleton. This
Signs and symptoms

For unknown reasons, children born with FOP have deformed big toes, possibly missing
a joint or simply presenting with a notable lump at the minor joint. The first "flare-up" that
causes endothelial cells to transform to mesenchymal stem cells and then to bone.[7]
Genetics
disorder in their family. There are some cases which have shown people inheriting the
mutation from one affected parent.[13]
FOP or Stone Man Syndrome is an autosomal dominant disorder that affects individuals
who are heterozygous with a homozygous recessive partner, therefore their children will
Diagnosis
have 50% chance of being affected. Two affected individuals can produce unaffected
children. The phenotypes of those who are homozygous dominant have more severe
Outbreaks may be measurable clinically by elevated levels of alkaline
effects compared to those with heterozygous phenotype. [8]
phosphatase and bone-specific alkaline phosphatase.[14]
The gene that causes ossification is normally deactivated after a fetus's bones are
Treatment
formed in the womb, but in patients with FOP, the gene keeps working. Aberrant bone
formation in patients with FOP occurs when injured connective tissue or muscle cells at
the sites of injury or growth incorrectly express an enzyme for bone repair
during apoptosis (self-regulated cell death), resulting in lymphocytes containing
excess bone morphogenetic protein 4 (BMP4) provided during the immune system
response. The bone that results occurs independently of the normal skeleton, forming its
own discrete skeletal elements. These elements, however, can fuse with normal skeletal
bone.[9] Interestingly, the diaphragm, tongue, and extra-ocular muscles are spared in this
process, as well as cardiac and smooth muscle.[2] Since the incorrect enzyme remains
unresolved within the immune response, the body continues providing the incorrect
BMP4-containing lymphocytes. BMP4 is a product that contributes to the development of
the skeleton in the normal embryo.[10]
DNA sequencing electropherograms of a typical FOP patient can differ when being
compared to two other patients. The cause of this mutation is in the ACVR1 gene. This
gene provides instruction for a protein known as morphogenetic protein (BMP). This
protein is responsible for growth and development of bone and muscles. Scientists and
researchers theorize that a mutation in the ACVR1 changes the shape of the receptor
and disrupts certain mechanisms that control the receptor's activity. There is a certain
molecule, otherwise known as ligands, that binds at the site to cause this reaction to
activate with which it forms a complex. Due to the mutation, however, the bind site is
modified and no longer stops the reaction.[11] The end result is an overgrowth of bone and
cartilage and fusion of joints.[12]
This type of genetic disorder is so rare that only 1 in 2 million people worldwide acquire
it. As it is such a rare disorder, only a few are reported at all. Most of the cases of FOP
were results of a new gene mutation: these people had no history of this particular
There is no known cure for FOP. Attempts to surgically remove the bone result in more
robust bone growth.[15] While under anesthesia, patients with FOP may face problems,
which include difficulties with intubation, restrictive pulmonary disease, and changes in
the electrical conduction system of the heart.[16] Activities that increase the risk of falling
should be avoided, as injuries from falling can provoke the growth of bone. [1]
In 1999, scientists discovered that squalamine in sharks[17] might be useful in treating
those suffering from FOP. Squalamine is antiangiogenic and can prevent the growth of
blood vessels in cartilaginous tissue, thus preventing creation of bone in sharks.
The Genaera Corporation announced a trial of squalamine in 2002[19][20]but terminated
about 2007. (Note that squalene is a different compound, also found in sharks, that has
no such properties.) Clinical trials of isotretinoin, etidronate with oralcorticosteroids,
and perhexiline maleate have failed to demonstrate effectiveness, though the variable
course of the disease and small numbers of patients leave some room for uncertainty.
[14]
In April 2013 the La Jolla Pharmaceutical Company was granted orphan drug status
for testing of 4-(6-(4-(piperazin-1-yl)phenyl_pyrazolo[1,5-a]pyrimidin-3-yl)quinoline

hydrochloride for treatment of FOP.[21]
Researchers believe that specific kinase inhibitors can be developed that will block the
aberrant ACVR1 activity, and are actively
investigating dorsomorphin and K02288 as lead compounds with the intention of
developing effective therapies. For example, the more potent dorsomorphin derivative
LDN-193189 reduced ossification in a transgenicmouse model, in which the engineering
of adult ACVR1 activity created an inflammation-dependent ossification sensitive
to corticosteroid treatment.[24]
Another major direction in research is the development of therapeutics based on allelespecific RNA interference to block the aberrant gene from directing production of ACVR1.
However, effective treatment by this means may require a better knowledge of what cell
types are responsible for the disease, so that inhibitory RNA can be produced from them
in the long term.[25]
Although this disorder is currently incurable, understanding and researching the cause of
bone formation in FOP could aid in the treatment of other bone disorders, especially
common ones such as fractures, hip replacement surgery, and other heterotopic
ossifications that occur in trauma or burn victims.[26]
Epidemiology
A study has determined that it affects approximately 1 in every 2 million people.[27]
Glycogen storage disease type XI

Glycogen storage disease type XI is a form of glycogen storage disease.

It is also known as "FanconiBickel syndrome", for Guido Fanconi and Horst Bickel, who
first described it in 1949.
It is associated with GLUT2,[3][4] a glucose transport protein which, when functioning
normally, allows glucose to exit several tissues, including the liver, nephrons,and
enterocytes of the intestines, and enter the blood. The syndrome results in hepatomegaly
secondary to glycogen accumulation, glucose and galactose intolerance, fasting
hypoglycaemia, a characteristic proximal tubular nephropathy and severe short stature.
Cases
Since the 1800s, there have been references in medicine describing people who
apparently "turned to stone"; some of these cases may be attributable to FOP.
The best known FOP case is that of Harry Eastlack (19331973). His condition began to
develop at the age of ten, and by the time of his death from pneumonia in November
Glycogen storage disease type XI

Glycogen storage disease type XI is a form of glycogen storage disease.
1973, six days before his 40th birthday, his body had completely ossified, leaving him
able to move only his lips.
It is also known as "FanconiBickel syndrome", for Guido Fanconi and Horst Bickel, who
first described it in 1949.
Shortly before Eastlack's death, he made it known that he wanted to donate his body to
It is associated with GLUT2,[3][4] a glucose transport protein which, when functioning

normally, allows glucose to exit several tissues, including the liver, nephrons,and
enterocytes of the intestines, and enter the blood. The syndrome results in hepatomegaly
secondary to glycogen accumulation, glucose and galactose intolerance, fasting
hypoglycaemia, a characteristic proximal tubular nephropathy and severe short stature.
science, in the hope that in death, he would be able to help find a cure for this littleunderstood and particularly cruel disease. Pursuant to his wishes, his preserved skeleton
is now kept at the Mtter Museum in Philadelphia, and has proven to be an invaluable
source of information in the study of FOP.
There have approximately been 700 confirmed cases across the globe from an
estimated 2500.
Hereditary inclusion body myopathy

Hereditary inclusion body myopathies (HIBM) are a heterogeneous group of genetic
disorders which have different symptoms. Generally, they are neuromuscular disorders
characterized by muscle weakness developing in young adults. Hereditary inclusion
body myopathies comprise both autosomal recessive and autosomal dominant muscle
disorders that have a variable expression (phenotype) in individual patients, but all share
similar structural features in the muscles.
encoding valosin-containing protein (VCP) on chromosome 9 (located at 9p13p12). See: OMIM # 167320 [5]
HIBMs are a group of muscle wasting disorders, which are uncommon in the general
world population. One autosomal recessive form of HIBM is known as IBM2, which is a
common genetic disorder amongst people of Iranian Jewish descent. IBM2 has also
been identified in other minorities throughout the world, including people of Asian
(Japanese and others), European, and South American origin, as well as Muslim patients
in the Middle Eastern, Palestinian, and Iranian origin. In Japan and many East Asian
countries, this disorder is known as Distal Myopathy with Rimmed Vacuoles (DMRV).
IBM2 causes progressive muscle weakness and wasting. Muscle wasting usually starts
around the age of 20 30 years, although young onset at 17 and old onset at 52 has
been recorded. As such, it affects the most productive times of our lives. It can progress
to marked disability within 10 15 years, confining many patients to the wheelchair. The
weakness and severity can vary from person to person. In some, weakness in the legs is
noticed first. In few others, the hands are weakened more rapidly than the legs.
Weakness is progressive, which means the muscle become weaker over time. IBM2
does not seem to affect the brain, internal organs or sensation. The quadriceps are
relatively spared, and remain strong until the late stages of disease, which is the reason
IBM2 is often referred to as Quadriceps Sparing Myopathy (QSM).
5. Inclusion body myopathy-3 (IBM3) is linked to mutations in a gene encoding

myosin heavy chain II proteins on chromosome 17 (located at 17p13.1). See:
OMIM # 605637[6]
More types of HIMBs, linked to other genes, may be identified in the future.
Signs and symptoms

Some early signs of HIBMs includes:
Classification
Difficulty walking on heels, and difficulty running;
Types of hereditary inclusion body myopathy:
Weak index finger;
Frequent loss of balance.
On muscle biopsy, the typical finding includes inclusion bodies, rimmed vacuoles
1. An autosomal dominant form (IBM1) where the quadriceps are one of the first
muscles to become weak. Needham (2007)[1] lists IBM1 under OMIM 601419: [1]
2. An autosomal recessive form (IBM2), common among people of Middle Eastern
and accumulation of aberrant proteins similar to those found in senile plaques
and Jewish heritage. This form mainly affects leg muscles, but with an unusual
of Alzheimer's disease (amyloid beta, hyperphosphorylated tau, amongst
distribution that spares the quadriceps: a so-called quadriceps-sparing myopathy
others)Reference
(QSM), the quadriceps are among the last muscles to become weak. See: OMIM
Genetics
# 600737.[2] Also see OMIM:605820(DMRV)[3].

The different forms have different mutations and inheritance patterns. See the detailed
3. Nonaka distal myopathy with rimmed vacuoles, essentially a form of IBM2. See:
OMIM # 605820: [4]
OMIM descriptions for details (given above).
Mechanisms
4. Inclusion body myopathy associated with Paget disease of bone and

frontotemporal dementia (IBMPFD), is linked to a slightly different gene,
The exact mechanisms of these diseases are not well understood.
Hereditary inclusion body myopathy (IBM) constitutes a unique group of neuromuscular
Treatment options for lower limb weakness such as foot drop can be through the use of
disorders characterized by adult-onset slowly progressive distal and proximal weakness,
Ankle Foot Orthoses (AFOs) which can be designed or selected by an Orthotist based
and a typical muscle pathology including rimmed vacuoles and filamentous inclusions.
upon clinical need for that patient. Sometimes tuning of rigid AFOs can enhance knee
Autosomal dominant (IMB3; OMIM 605637 [7]) and autosomal recessive (IBM2; OMIM
stability.
600737 [8]) forms have been described. The autosomal recessive form, first
characterized in Jews of Persian descent, is a myopathy that affects mainly leg muscles,
There was an initial study done at the National Human Genome Research
but with an unusual distribution that spares the quadriceps, so-called quadriceps-sparing
Institute in Bethesda, MD testing the efficacy of administering sialic acid to patients with
myopathy (QSM). This disorder was subsequently found in other Middle Eastern families,
HIBM. Because the study cohort was so small, no significant results were determined.
the gene was mapped to 9p13-p12, and in 104 affected persons from 47 Middle Eastern
Anecdotal reports by patients suggested limb muscle strength was improved. Further,
families the same mutation in homozygous state was found in the GNE gene. [2] Affected
patients with HIBM have reported taking sialic acid on their own. A number of labs are
individuals in families of other ethnic origins were found to be compound heterozygotes
studying sialic acid and its derivatives as a potential therapeutic for HIBM.
for other distinct mutations in the GNE gene. From OMIM 603824. [9]
Diagnosis
The most useful information for accurate diagnosis is the symptoms and weakness
pattern. If the quadriceps are spared but the hamstrings and iliopsoas are severely
affected in a person between ages of 20 - 40, it is very likely HIBM will be at the top of
the differential diagnosis. The doctor may order any or all of the following tests to
ascertain if a patient has IBM2:
Blood test for serum Creatine Kinase (CK or CPK);
Nerve Conduction Study (NCS) / Electomyography (EMG);
Muscle Biopsy;
Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to

determine true sparing of quadriceps;
Blood Test or Buccal swab for genetic testing;
Treatment
Treatment is palliative, not curative.
Hypertonia
Hypertonia is a term sometimes used synonymously with spasticity in the literature

surrounding damage to the central nervous system, namely upper motor brain lesions.
[1]
Impaired ability of damaged motor neurons to regulate descending pathways gives rise
to disordered spinal reflexes, increased excitability of muscle spindles, and
decreased synaptic inhibition.[2] These consequences result in abnormally
increased muscle tone of symptomatic muscles.[3] Some authors suggest that the current
definition for spasticity, the velocity-dependent over-activity of the stretch reflex, is not
sufficient as it fails to take into account patients exhibiting increased muscle tone in the
absence of stretch reflex over-activity. They instead suggest that reversible
hypertonia is more appropriate and represents a treatable condition that is responsive
to various therapy modalities like drug and/or physical therapy.[4]
Symptoms associated with central nervous systems disorders are classified into positive
and negative categories. Positive symptoms include those that increase muscle activity
through hyper-excitability of the stretch reflex (i.e., rigidity and spasticity) where negative
symptoms include those of insufficient muscle activity (i.e. weakness) and reduced motor
function.[5] Often the two classifications are thought to be separate entities of a disorder;
however, some authors propose that they may be closely related.
Physical interventions
Physiotherapy has been shown to be effective in controlling hypertonia through the use
of stretching aimed to reduce motor neuron excitability.[8] The aim of each physical
therapy session will be to inhibit excessive tone as far as possible, give the patient a
sensation of normal position and movement, and to facilitate normal movement patterns.
While static stretch has been the classical means to increase range of motion, PNF
Pathophysiology
stretching has been used in many clinical settings to effectively reduce muscle spasticity.
[9]
Hypertonia is caused by upper motor neuron lesions which may result from injury,
disease, or conditions that involve damage to the central nervous system. Motor
Icing and other topical anesthetics may decrease the reflexive activity for short period of
neuronal hyperactivity occurs due to loss of inhibition of cells of the anterior horn of the
time in order to facilitate motor function. Inhibitory pressure (applying firm pressure over
spinal cord resulting from reticulospinal tract damage. Different patterns of muscle
muscle tendon), promoting body heat retention, rhythmic rotation (slow repeated rotation
weakness or hyperactivity can occur based on the location of the lesion, causing a
of affected body part to stimulate relaxation)[10] have also been proposed as potential
multitude of neurological symptoms, including spasticity, rigidity, or dystonia.[7]
methods to decrease hypertonia. Aside from static stretch casting and splinting
techniques are extremely valuable to extend joint range of motion lost to hypertonicity [11] A
Spastic hypertonia involves uncontrollable muscle spasms, stiffening or straightening out
more unconventional method for limiting tone is to deploy quick repeated passive
of muscles, shock-like contractions of all or part of a group of muscles, and
movements to an involved joint in cyclical fashion; this has also been demonstrated to
abnormalmuscle tone. It is seen in disorders such as cerebral palsy, stroke, and spinal
show results on persons without physical disabilities.[8] For a more permanent state of
cord injury. Rigidity is a severe state of hypertonia where muscle resistance occurs
improvement, exercise and patient education is imperative.[10] Isokinetic,[12][13][14][15] aerobic,[16]
throughout the entire range of motion of the affected joint independent of velocity. It is
[17][18]
andstrength training[19][20][21][22] exercises should be performed as prescribed by a
frequently associated with lesions of the basal ganglia. Individuals with rigidity present
physiotherapist, and stressful situations that may cause increased tone should be
with stiffness, decreased range of motion and loss of motor control. Dystonic hypertonia
minimized or avoided.[10]
refers to muscle resistance to passive stretching (in which a therapist gently stretches
the inactive contracted muscle to a comfortable length at very low speeds of movement)
Pharmaceutical interventions
and a tendency of a limb to return to a fixed involuntary (and sometimes abnormal)

posture following movement.
Management
Baclofen, diazepam and dantrolene remain the three most commonly used
pharmacologic agents in the treatment of spastic hypertonia. Baclofen is generally the
drug of choice for spinal cord types of spasticity, while sodium dantrolene is the only
agent which acts directly on muscle tissue. Tizanidine is also
Therapeutic interventions are best individualized to particular patients.

Basic principles of treatment for hypertonia are to 1) avoid noxious stimuli and 2) provide
frequent range of motion exercise.
available. Phenytoin with chlorpromazine may be potentially useful if sedation does not
limit their use. Ketazolam, not yet available in the United States, may be a significant
addition to the pharmacologic armamentarium.Intrathecal administration of antispastic
medications allows for high concentrations of drug near the site of action, which limits
side effects.
Macrophagic myofasciitis
Macrophagic Myofasciitis, or MMF, is a rare muscle disease identified in 1993. The

disease is characterized by microscopic lesions found in muscle biopsies that show
infiltration of muscle tissue by PAS-positive macrophages.[1] Specific causes of MMF are
unknown. Intramuscular injections aluminium-containing vaccines have been implicated.
[1]
Many of those affected with the disease had previously been treated
for malaria with chloroquine or hydroxychloroquine for malaria.[2]
Clinical symptoms include muscle pain, joint pain, muscle weakness, fatigue, fever, and
muscle tenderness. A diagnosis can only be identified with an open muscle biopsy of the
vaccinated muscle.[3]
Studies at the University of Paris have shown that MMF lesions result when the
aluminum hydroxide adjuvant from a vaccine remains embedded in the tissue and
causes a steady immune reaction.
Glycogen storage disease

(Redirected from Glycogen storage diseases)
Glycogen storage disease (GSD, also glycogenosis and dextrinosis) is the result of
defects in the processing of glycogensynthesis or breakdown within muscles, liver, and
other cell types.[1] GSD has two classes of cause: genetic and acquired. Genetic GSD is
caused by any inborn error of metabolism (genetically defective enzymes) involved in
these processes. In livestock, acquired GSD is caused by intoxication with
the alkaloid castanospermine.[2]
Overall, according to a study in British Columbia, approximately 2.3 children per 100 000
births (1 in 43,000) have some form of glycogen storage disease. [3] In the United States,
they are estimated to occur in 1 per 20,000-25,000 births. [4] A Dutch study estimated it to
be 1 in 40,000.[5]
Metabolic myopathy
Types
There are eleven (11) distinct diseases that are commonly considered to be glycogen
storage diseases (some previously thought to be distinct have been reclassified).
(Although glycogen synthase deficiency does not result in storage of extra glycogen in
the liver, it is often classified with the GSDs as type 0 because it is another defect of
glycogen storage and can cause similar problems.)
Metabolic myopathies are myopathies that result from defects in biochemical metabolism
that primarily affect muscle. They include:
1- Glycogen storage diseases
2- Lipid storage disorder

3- Phosphocreatine stores disorder
GSD type VIII: In the past, considered a distinct condition.[6] Now classified with
VI.[7] Has been described as X-linked recessive.[8]
GSD type X: In the past, considered a distinct condition.[9][10] Now classified with
VI.
disease. They are generally inherited in an autosomal recessive fashion, but

notably Fabry disease is X-linked. Taken together, sphingolipidoses have an incidence of
approximately 1 in 10.000.Enzyme replacement therapy is available to treat mainly Fabry
disease and Gaucher disease, and people with these types of sphingolipidoses may live
well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile
forms, but progression may be mild for juvenile- or adult-onset forms.
Lipid storage disorder

Some of the sphingolipidoses may alternatively be classified into either GM1

gangliosidoses or GM2 gangliosidoses. TaySachs disease belongs to the latter.
Other
Lipid storage disorders (or lipidoses) are a group of inherited metabolic disorders in
which harmful amounts of lipids (fats) accumulate in some of the bodys cells and
tissues.[1] People with these disorders either do not produce enough of one of
theenzymes needed to metabolize lipids or they produce enzymes that do not work
properly. Over time, this excessive storage of fats can cause permanent cellular and
tissue damage, particularly in the brain, peripheral nervous
system, liver, spleen and bone marrow.
Other lipid storage disorders that are generally not classified as sphingolipidoses
Lipids are broadly defined as any fat-soluble (lipophilic), naturally occurring molecule,
such as fats, oils, waxes, steroids (such ascholesterol and estrogen), sterols and others.
Lipids are important parts of the membranes found within and between each cell and in
the myelin sheath that coats and protects the nerves.
occurs when both parents carry and pass on a copy of the faulty gene, but neither parent
Inside the cells, lysosomes convert, or metabolize, lipids and proteins into smaller
components to provide energy for the body.
either copy of the defective gene. Children of either gender can be affected by an
Classification
Disorders that store this intracellular material are part of the lysosomal storage
diseases family of disorders.
Sphingolipidoses
Main article: Sphingolipidosis
Many lipid storage disorder can be classified into the subgroup of sphingolipidoses, as
they relate to sphingolipid metabolism. Members of this group include Niemann-Pick
disease, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs
disease, Metachromatic leukodystrophy, multiple sulfatase deficiency and Farber
include fucosidosis, Schindler disease and Wolman disease.
Inheritance
Lipid storage diseases can be inherited two ways: Autosomal recessive inheritance
show signs and symptoms of the condition and is not affected by the disorder. Each child
born to these parents have a 25 percent chance of inheriting both copies of the defective
gene, a 50 percent chance of being a carrier, and a 25 percent chance of not inheriting
autosomal recessive this pattern of inheritance.
X-linked recessive (or sex linked) inheritance occurs when the mother carries the
affected gene on the X chromosome that determines the childs gender and passes it to
her son. Sons of carriers have a 50 percent chance of inheriting the disorder. Daughters
have a 50 percent chance of inheriting the X-linked chromosome but usually are not
severely affected by the disorder. Affected men do not pass the disorder to their sons but
their daughters will be carriers for the disorder.
Diagnosis
Diagnosis of the lipid storage disorders can be achieved through the use of several tests.
These tests include clinical examination, biopsy, genetic testing, molecular analysis of
cells or tissues, and enzyme assays. Certain forms of this disease can also be
diagnosed through urine testing which will detect the stored material. Prenatal testing is
phosphocreatine. The reversible phosphorylation of creatine (i.e., both the forward and
also available to determine if the fetus will have the disease or is a carrier.[2]
backward reaction) is catalyzed by severalcreatine kinases. The presence of creatine
Treatment
There are no specific treatments for lipid storage disorders, however, there are some
highly effective enzyme replacement therapies for people with type 1 Gaucher disease
and some patients with type 3 Gaucher disease. There are other treatments such as the
prescription of certain drugs like phenytoin and carbamazepine to treat pain for patients
withFabry disease. Furthermore, gene thereapies and bone marrow transplantation may
prove to be effective for certain lipid storage disorders.[3] Diet restrictions do not help
prevent the buildup of lipids in the tissues.
kinase (CK-MB, MB for muscle/brain) in blood plasma is indicative of tissue damage and
is used in the diagnosis of myocardial infarction.[1] The cell's ability to generate
phosphocreatine from excess ATP during rest, as well as its use of phosphocreatine for
quick regeneration of ATP during intense activity, provides a spatial and temporal buffer
of ATPconcentration. In other words, phosphocreatine acts as high-energy reserve in a
coupled reaction; the energy given off from donating the phosphate group is used to
regenerate the other compound - in this case, ATP. Phosphocreatine plays a particularly
important role in tissues that have high, fluctuating energy demands such as muscle and
brain.
Phosphocreatine
Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is
a phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of highenergy phosphates in skeletal muscle and the brain.
Chemistry
Phosphocreatine is formed from parts of three amino acids: arginine (Arg), glycine (Gly),
and methionine (Met). It can be synthesized by formation of guanidinoacetate from Arg
and Gly (in kidney) followed by methylation (S-adenosyl methionine is required) to
creatine (in liver), and phosphorylation by creatine kinase (ATP is required) to
phosphocreatine (in muscle); catabolism: dehydration to form the cyclic Schiff
base creatinine. Phosphocreatine is synthesized in the liver and transported to the
muscle cells, via the bloodstream, for storage.
The creatine phosphate shuttle facilitates transport of high energy phosphate
from mitochondria.
Function
Phosphocreatine can anaerobically donate a phosphate group to ADP to
form ATP during the first 2 to 7 seconds following an intense muscular or neuronal effort.
Conversely, excess ATP can be used during a period of low effort to convert creatine to
Muscle atrophy
Muscle atrophy is defined as a decrease in the mass of the muscle; it can be a partial or
complete wasting away of muscle, and is most commonly experienced when persons
suffer temporary disabling circumstances such as being restricted in movement and/or
confined to bed as when hospitalized. When a muscle atrophies, this leads to muscle
weakness, since the ability to exert force is related to mass. Modern medicine's
understanding of the quick onset of muscle atrophy is a major factor behind the practice
of getting hospitalized patients out of bed and moving about as active as possible as
soon as is feasible, despite sutures, wounds, broken bones and pain.
Muscle atrophy results from a co-morbidity of several common diseases,
including cancer, AIDS, congestive heart failure, COPD(chronic obstructive pulmonary
disease), renal failure, and severe burns; patients who have "cachexia" in these disease
settings have a poor prognosis. Moreover, starvation eventually leads to muscle atrophy.
Disuse of the muscles, such as when muscle tissue is immobilized for even a few days of
unuse when the patient has a primary injury such as an immobilized broken bone (set
in a cast or immobilized in traction), for example will also lead rapidly to disuse atrophy.
Minimizing such occurrences as soon as possible is a primary mission
of occupational and physical therapists employed within hospitals working in coordination with orthopedic surgeons.
Neurogenic atrophy, which has a similar effect, is muscle atrophy resulting from damage
to the nerve which stimulates the muscle, causing a shriveling around otherwise healthy
limbs. Also, time in a circa zero g environment without exercise will lead to atrophy. This
is partially due to the smaller amount of exertion needed to move about, and the fact that
muscles are not used to maintain posture. In a similar effect, patients with a broken leg
joint undergoing as little as three weeks of traction can lose enough back and buttocks
muscle mass and strength as to have difficulty sitting without assistance, and experience
pain, stress and burning even after a very short ten-minute exposure, when such
positioning is contrived during recovery.
Clinical settings
There are many diseases and conditions which cause a decrease in muscle mass,
known as atrophy, including: inactivity, as seen when a cast is put on a limb, or upon
extended bedrest (which can occur during a prolonged illness); cachexia - which is a
syndrome that is a co-morbidity of cancer and congestive heart failure; chronic
obstructive pulmonary disease; burns, liver failure, etc., and the wasting Dejerine Sottas
syndrome (HSMN Type III). Other syndromes or conditions which can induce skeletal
muscle atrophy are liver disease, and starvation.
In addition to the simple loss of muscle mass (atrophy), or the age-related decrease in
muscle function (sarcopenia), there are other diseases which may be caused by
structural defects in the muscle (muscular dystrophy), or by inflammatory reactions in the
body directed against muscle (the myopathies).
Pathophysiology
Muscle atrophy occurs by a change in the normal balance between protein synthesis and
protein degradation. During atrophy, there is a down-regulation of protein synthesis
pathways, and an activation protein degradation.[1] The particular protein degradation
pathway which seems to be responsible for much of the muscle loss seen in a muscle
undergoing atrophy is the ATP-dependent ubiquitin/proteasomepathway. In this system,
particular proteins are targeted for destruction by the ligation of at least four copies of a
small peptide calledubiquitin onto a substrate protein. When a substrate is thus "polyubiquitinated", it is targeted for destruction by the proteasome. Particular enzymes in the
ubiquitin/proteasome pathway allow ubiquitination to be directed to some proteins but not
others - specificity is gained by coupling targeted proteins to an "E3 ubiquitin ligase".
Each E3 ubiquitin ligase binds to a particular set of substrates, causing their
ubiquitination.
Quality of life
Potential treatment
Muscular atrophy decreases qualities of life as the sufferer becomes unable to perform
certain tasks or worsen the risks of accidents while performing those (like walking).
Muscle atrophy can be opposed by the signaling pathways which induce muscle
Muscular atrophy increases the risks of falling in conditions such as IBM (inclusion body
hypertrophy, or an increase in muscle size. Therefore one way in which exercise induces
myositis). Muscular atrophy affects a high number of the elderly.
an increase in muscle mass is to downregulate the pathways which have the opposite
effect.
Other muscle diseases, distinct from atrophy

One important rehabilitation tool for muscle atrophy includes the use of functional
During aging, there is a gradual decrease in the ability to maintain skeletal muscle
electrical stimulation to stimulate the muscles. This has seen a large amount of success
function and mass. This condition is called "sarcopenia". The exact cause of sarcopenia
in the rehabilitation of paraplegic patients.[2]
is unknown, but it may be due to a combination of the gradual failure in the "satellite
cells" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or
Since the absence of muscle-building amino acids can contribute to muscle wasting (that
the availability of critical secreted growth factors which are necessary to maintain muscle
which is torn down must be rebuilt with like material), amino acid therapy may be helpful
mass and satellite cell survival.
for regenerating damaged or atrophied muscle tissue. The branched-chain amino acids
or BCAAs (leucine, isoleucine, and valine) are critical to this process, in addition
to lysineand other amino acids.
In severe cases of muscular atrophy, the use of an anabolic steroid such as
During hibernation, bears spend four to seven months of inactivity and anorexia without
methandrostenolone is administered to patients as a potential cure. A novel class of
undergoing muscle atrophy and protein loss.[5] There are a few known factors that
drugs, called SARM (selective androgen receptor modulators) are being investigated
contribute to the sustaining of muscle tissue. During the summer period, bears take
with promising results. They would have fewer side-effects, while still promoting muscle
advantage of the nutrition availability and accumulate muscle protein. The protein
and bone tissue growth and regeneration. These claims are, however, yet to be
balance at time of dormancy is also maintained by lower levels of protein breakdown
confirmed in larger clinical trials.
during the winter time.[5] At times of immobility, muscle wasting in bears is also
suppressed by a proteolytic inhibitor that is released in circulation.[4] Another factor that
Quantification
contributes to the sustaining of muscle strength in hibernating bears is the occurrence of
A CT scan can distinguish muscle tissue from other tissues and thereby estimate the
amount of muscle tissue in the body.
periodic voluntary contractions and involuntary contractions from shivering during torpor.
[7]
The three to four daily episodes of muscle activity are responsible for the maintenance
of muscle strength and responsiveness in bears during hibernation.
Fast loss of muscle tissue (relative to normal turnover), can be approximated by the
amount of urea in the urine. The equivalent nitrogen content (in gram) of urea (in mmol)
can be estimated by the conversion factor 0.028 g/mmol.[3] Furthermore, 1 gram of
nitrogen is roughly equivalent to 6 gram of protein, and 1 gram of protein is roughly
equivalent to 4 gram of muscle tissue. Subsequently, in situations such as muscle
wasting, 1 mmol of excessive urea in the urine (as measured by urine volume in litres
multiplied by urea concentration in mmol/l) roughly corresponds to a muscle loss of 0.67
gram.
Hibernation
Inactivity and starvation in mammals lead to atrophy of skeletal muscle, accompanied by
a smaller number and size of the muscle cells as well as lower protein content. [4] In
humans, prolonged periods of immobilization, as in the cases of bed rest or astronauts
flying in space, are known to result in muscle weakening and atrophy. Such
consequences are also noted in small hibernating mammals like the golden-mantled
ground squirrels and brown bats.[5]
Muscle fatigue
Bears are an exception to this rule; species in the family Ursidae are famous for their
Muscle fatigue, or physical fatigue, is the decline in ability of a muscle to
ability to survive unfavorable environmental conditions of low temperatures and limited
generate force. It can be a result of vigorous exercise but abnormal fatigue may be
nutrition availability during winter by means of hibernation. During that time, bears go
caused by barriers to or interference with the different stages of muscle contraction.
through a series of physiological, morphological and behavioral changes. Their ability to
There are two main causes of muscle fatigue. The limitations of a nerves ability to
maintain skeletal muscle number and size at time of disuse is of significant importance.
generate a sustained signal(neural fatigue) and the reduced ability of the muscle fiber to
[6]
contract (metabolic fatigue).
Muscle contraction
Main article: Muscle contraction
Muscle cells work by detecting a flow of electrical impulses from the brain which signals
them to contract through the release of calcium by the sarcoplasmic reticulum. Fatigue
(reduced ability to generate force) may occur due to the nerve, or within the muscle cells
themselves.
2. Accumulation of substances (metabolites) within the muscle fiber, which interfere

either with the release of calcium (Ca2+) or with the ability of calcium to stimulate
muscle contraction.
Substrates
Substrates within the muscle generally serve to power muscular contractions. They
include molecules such as adenosine triphosphate (ATP), glycogen and creatine
Nervous fatigue
phosphate. ATP binds to the myosin head and causes the ratchetting that results in
Nerves are responsible for controlling the contraction of muscles, determining the
ATP can be rapidly regenerated within the muscle cells from adenosine
number, sequence and force of muscular contraction. Most movements require a force
far below what a muscle could potentially generate, and barring pathological nervous
fatigue, is seldom an issue. For extremely powerful contractions that are close to the
upper limit of a muscle's ability to generate force, nervous fatigue can be a limiting factor
in untrained individuals. In novice strength trainers, the muscle's ability to generate force
is most strongly limited by nerves ability to sustain a high-frequency signal. After a
period of maximum contraction, the nerves signal reduces in frequency and the force
generated by the contraction diminishes. There is no sensation of pain or discomfort, the
muscle appears to simply stop listening and gradually cease to move, often going
backwards. As there is insufficient stress on the muscles and tendons, there will often be
contraction according to the sliding filament model. Creatine phosphate stores energy so
diphosphate (ADP) and inorganic phosphate ions, allowing for sustained powerful
contractions that last between 57 seconds. Glycogen is the intramuscular storage form
of glucose, used to generate energy quickly once intramuscular creatine stores are
exhausted, producing lactic acid as a metabolic byproduct.
Substrate shortage is one of the causes of metabolic fatigue. Substrates are depleted
during exercise, resulting in a lack of intracellular energy sources to fuel contractions. In
essence, the muscle stops contracting because it lacks the energy to do so.
Metabolites
no delayed onset muscle soreness following the workout. Part of the process of strength
Metabolites are the substances (generally waste products) produced as a result of
training is increasing the nerve's ability to generate sustained, high frequency signals
muscular contraction. They include chloride, potassium, lactic
which allow a muscle to contract with its greatest force. It is this neural training that
acid, ADP, magnesium (Mg2+),reactive oxygen species, and inorganic phosphate.
causes several weeks worth of rapid gains in strength, which level off once the nerve is
Accumulation of metabolites can directly or indirectly produce metabolic fatigue within
generating maximum contractions and the muscle reaches its physiological limit. Past
muscle fibers through interference with the release of calcium (Ca2+) from the
this point, training effects increase muscular strength through myofibrilar or
sarcoplasmic reticulum or reduction of the sensitivity of contractile
sarcoplasmic hypertrophy and metabolic fatigue becomes the factor limiting contractile
molecules actin and myosin to calcium.
force.
Metabolic fatigue
Chloride
Intracellular chloride partially inhibits the contraction of muscles. Namely, it prevents
Though not universally used, metabolic fatigue is a common term for the reduction in
muscles from contracting due to "false alarms", small stimuli which may cause them to
contractile force due to the direct or indirect effects of two main factors:
contract (akin to myoclonus). This natural brake helps muscles respond solely to the
1. Shortage of fuel (substrates) within the muscle fiber
conscious control or spinal reflexes[citation needed] but also has the effect of reducing the force
of conscious contractions.
Potassium[
muscle undergoes a conformational change during exercise, resulting in "leaky"

channels that are deficient in Calcium release. These "leaky" channels may be a
High concentrations of potassium (K ) also causes the muscle cells to decrease in

+
contributor to muscle fatigue and decreased exercise capacity.[3]
efficiency, causing cramping and fatigue. Potassium builds up in the t-tubule system and
around the muscle fiber as a result of action potentials. The shift in K+ changes the
Effect on performance
membrane potential around the muscle fiber. The change in membrane potential causes
Fatigue has been found to play a big role in limiting performance in just about every
a decrease in the release of calcium (Ca2+) from the sarcoplasmic reticulum.[1]
individual in every sport. In research studies, participants were found to show reduced
voluntary force production in fatigued muscles (measured with concentric, eccentric, and
Lactic acid
isometric contractions), vertical jump heights, other field tests of lower body power,
It was once believed that lactic acid build-up was the cause of muscle fatigue. The
reduced throwing velocities, reduced kicking power and velocity, less accuracy in
assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to
throwing and shooting activities, endurance capacity, anaerobic capacity, anaerobic
contract. The impact of lactic acid on performance is now uncertain, it may assist or
power, mental concentration, and many other performance parameters when sport
hinder muscle fatigue.
specific skills are examined.
[2]
Produced as a by-product of fermentation, lactic acid can increase intracellular acidity of
Electromyography
muscles. This can lower the sensitivity of contractile apparatus to Ca but also has the
2+
effect of increasing cytoplasmic Ca2+ concentration through an inhibition of the chemical
Electromyography is a research technique that allows researchers to look at muscle
pump that actively transports calcium out of the cell. This counters inhibiting effects of
recruitment in various conditions, by quantifying electrical signals sent to muscle fibers
potassium on muscular action potentials. Lactic acid also has a negating effect on the
through motor neurons. In general, fatigue protocols have shown increases in EMG data
chloride ions in the muscles, reducing their inhibition of contraction and leaving
over the course of a fatiguing protocol, but reduced recruitment of muscle fibers in tests
potassium ions as the only restricting influence on muscle contractions, though the
of power in fatigued individuals. In most studies, this increase in recruitment during
effects of potassium are much less than if there were no lactic acid to remove the
exercise correlated with a decrease in performance (as would be expected in a fatiguing
chloride ions. Ultimately, it is uncertain if lactic acid reduces fatigue through increased
individual).
intracellular calcium or increases fatigue through reduced sensitivity of contractile

proteins to Ca2+.
Median power frequency is often used as a way to track fatigue using EMG. Using the
median power frequency, raw EMG data is filtered to reduce noise and then relevant time
Pathology
windows are Fourier Transformed. In the case of fatigue in a 30-second isometric

contraction, the first window may be the first second, the second window might be at
Muscle weakness may be due to problems with the nerve supply, neuromuscular
second 15, and the third window could be the last second of contraction (at second 30).
disease (such as myasthenia gravis) or problems with muscle itself. The latter category
Each window of data is analyzed and the median power frequency is found. Generally,
includespolymyositis and other muscle disorders
the median power frequency decreases over time, demonstrating fatigue. Some reasons
Molecular Mechanisms
Muscle fatigue may be due to precise molecular changes that occur in vivo with
sustained exercise. It has been found that the Ryanodine receptor present in skeletal
why fatigue is found are due to action potentials of motor units having a similar pattern of
repolarization, fast motor units activating and then quickly deactivating while slower
motor units remain, and conduction velocities of the nervous system decreasing over
time.
Muscle weakness
Muscle weakness or myasthenia (my- from Greek meaning "muscle" + -asthenia

meaning "weakness") is a lack of muscle strength. The causes are many and
can be divided into conditions that have either true or perceived muscle weakness. True
muscle weakness is a primary symptom of a variety of skeletal muscle diseases,
including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular
junction disorders, such as myasthenia gravis. Muscle weakness can also be caused by
low levels of potassium and other electrolytes within muscle cells.
True and perceived muscle weakness

Muscle weakness can be classified as either "true" or "perceived" based on its cause. [1]
True muscle weakness (or neuromuscular weakness) describes a condition

where the force exerted by the muscles is less than would be expected, for
example muscular dystrophy.
Perceived muscle weakness (or non-neuromuscular weakness) describes a

condition where a person feels more effort than normal is required to exert a given
amount of force but actual muscle strength is normal, for example chronic fatigue
syndrome.[2]
In some conditions, such as myasthenia gravis muscle strength is normal when resting,
but true weakness occurs after the muscle has been subjected to exercise. This is also
true for some cases of chronic fatigue syndrome, where objective post-exertion muscle
weakness with delayed recovery time has been measured and is a feature of some of
Neuromuscular fatigue
the published definitions.[3][4][5][6][7][8]

Nerves control the contraction of muscles by determining the number, sequence, and
Proximal and distal muscle weakness
force of muscular contraction. When a nerve experiences synaptic fatigue it becomes

unable to stimulate the muscle that it innervates. Most movements require a force far
Muscle weakness can also be classified as either "proximal" or "distal" based on the
below what a muscle could potentially generate, and barring pathology, neuromuscular
location of the muscles that it affects. Proximal muscle weakness affects muscles closest
fatigue is seldom an issue.
to the body's midline, while distal muscle weakness affects muscles further out on
the limbs.
For extremely powerful contractions that are close to the upper limit of a muscle's ability
to generate force, neuromuscular fatigue can become a limiting factor in untrained
Proximal muscle weakness can be seen in Cushing's Syndrome and Hypothyroidism.
Grading
The severity of muscle weakness can be classified into different "grades" based on the
following criteria:[9][10]
Grade 0: No contraction or muscle movement
Grade 1: Trace of contraction, but no movement at the joint
Grade 2: Movement at the joint with gravity eliminated
individuals.In novice strength trainers, the muscle's ability to generate force is most
strongly limited by nerves ability to sustain a high-frequency signal. After an extended
muscle appears to simply stop listening and gradually cease to move, often lengthening.
As there is insufficient stress on the muscles and tendons, there will often be no delayed
onset muscle soreness following the workout. Part of the process of strength training is
increasing the nerve's ability to generate sustained, high frequency signals which allow a
muscle to contract with their greatest force. It is this "neural training" that causes several
weeks worth of rapid gains in strength, which level off once the nerve is generating
maximum contractions and the muscle reaches its physiological limit. Past this point,
training effects increase muscular strength through myofibrillar or
Grade 3: Movement against gravity, but not against added resistance
force.
Grade 4: Movement against external resistance, but less than normal
Grade 5: Normal strength
Types of neuromuscular fatigue
Central fatigue
Central fatigue is a reduction in the neural drive or nerve-based motor command to
working muscles that results in a decline in the force output.[13][14][15] It has been suggested
that the reduced neural drive during exercise may be a protective mechanism to prevent
Neuromuscular fatigue can be classified as either "central" or "peripheral" depending on
organ failure if the work was continued at the same intensity.[16][17] There has been a great
its cause. Central muscle fatigue manifests as an overall sense of energy deprivation,
deal of interest in the role of serotonergic pathways for several years because its
while peripheral muscle fatigue manifests as a local, muscle-specific inability to do work.
concentration in the brain increases with motor activity.[18][19][20] During motor activity,
[11][12]
serotonin released in synapses that contact motoneurons promotes muscle contraction.

[21]
During high level of motor activity, the amount of serotonin released increases and a
spillover occurs. Serotonin binds to extrasynaptic receptors located on the axon initial
segment of motoneurons with the result that nerve impulse initiation and thereby muscle
Lactic acid hypothesis
contraction are inhibited.[22]

It was once believed that lactic acid build-up was the cause of muscle fatigue.[24] The
Peripheral muscle fatigue
Peripheral muscle fatigue during physical work is an inability for the body to supply
sufficient energy or other metabolites to the contracting muscles to meet the increased
energy demand. This is the most common case of physical fatigueaffecting a
national
muscles. This can lower the sensitivity of contractile apparatus to calcium ions (Ca2+) but
[where?]
average of 72% of adults in the work force in 2002. This causes contractile
dysfunction that manifests in the eventual reduction or lack of ability of a single muscle or
also has the effect of increasing cytoplasmic Ca2+ concentration through an inhibition of
local group of muscles to do work. The insufficiency of energy, i.e. sub-optimal aerobic
the chemical pump that actively transports calcium out of the cell. This counters inhibiting
metabolism, generally results in the accumulation of lactic acid and
effects of potassium ions (K+) on muscular action potentials. Lactic acid also has a
other acidic anaerobic metabolic by-products in the muscle, causing the stereotypical
negating effect on the chloride ions in the muscles, reducing their inhibition of contraction
burning sensation of local muscle fatigue, though recent studies have indicated
and leaving K+ as the only restricting influence on muscle contractions, though the effects
otherwise, actually finding that lactic acid is a source of energy.[23]
of potassium are much less than if there were no lactic acid to remove the chloride ions.
Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular
The fundamental difference between the peripheral and central theories of muscle
calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca 2+.
fatigue is that the peripheral model of muscle fatigue assumes failure at one or more
sites in the chain that initiates muscle contraction. Peripheral regulation therefore
depends on the localized metabolic chemical conditions of the local muscle affected,
whereas the central model of muscle fatigue is an integrated mechanism that works to
preserve the integrity of the system by initiating muscle fatigue through muscle
derecruitment, based on collective feedback from the periphery, before cellular or organ
failure occurs. Therefore the feedback that is read by this central regulator could include
chemical and mechanical as well as cognitive cues. The significance of each of these
factors will depend on the nature of the fatigue-inducing work that is being performed.
Pathophysiology
Main article: muscle contraction
Muscle cells work by detecting a flow of electrical impulses from the brain which signals
themselves. New research from scientists at Columbia University suggests that muscle
Though not universally used, "metabolic fatigue" is a common alternative term for
fatigue is caused by calcium leaking out of the muscle cell. This causes there to be less
peripheral muscle weakness, because of the reduction in contractile force due to the
calcium available for the muscle cell. In addition an enzyme is proposed to be activated
direct or indirect effects of the reduction of substrates or accumulation of metabolites
by this released calcium which eats away at muscle fibers.[25]
within the muscle fiber. This can occur through a simple lack of energy to fuel
contraction, or through interference with the ability of Ca2+ to
stimulate actin and myosin to contract.
critical illness myopathy, metabolic, and myopathies with other systemic disorders.
Patients with systemic myopathies often present acutely or sub acutely. On the other
hand, familial myopathies or dystrophies generally present in a chronic fashion with
exhausted, producing lactic acid as a metabolic byproduct. Contrary to common belief,
exceptions of metabolic myopathies where symptoms on occasion can be precipitated
lactic acid accumulation doesn't actually cause the burning sensation we feel when we
acutely. Most of the inflammatory myopathies can have a chance association with
exhaust our oxygen and oxidative metabolism, but in actuality, lactic acid in presence of
malignant lesions; the incidence appears to be specifically increased only in patients with
oxygen recycles to produce pyruvate in the liver which is known as the Cori cycle.
dermatomyositis.[4]
Substrates produce metabolic fatigue by being depleted during exercise, resulting in a
Classes
lack of intracellular energy sources to fuel contractions. In essence, the muscle stops
contracting because it lacks the energy to do so.
There are many types of myopathy. ICD-10 codes are provided here where available.
Inherited forms
Myopathy
In medicine, a myopathy is a muscular disease[2] in which the muscle fibers do not
function for any one of many reasons, resulting inmuscular weakness. "Myopathy" simply
means muscle disease (myo- Greek "muscle" + pathos -pathy Greek "suffering").
This meaning implies that the primary defect is within the muscle, as opposed to the
nerves ("neuropathies" or "neurogenic" disorders) or elsewhere (e.g., the brain
etc.). Muscle cramps, stiffness, and spasm can also be associated with myopathy.
Capture Myopathy, or Shock Disease, is a little-studied condition observed in wild
animals such as hares and birds that have been captured or handled. [3] The condition is
usually lethal and stress has been identified as the single most determining factor,
exacerbated by muscle exertion.
Muscular disease can be classified as neuromuscular or musculoskeletal in nature.
Some conditions, such as myositis, can be considered both neuromuscular and
musculoskeletal.
(G71.0) Dystrophies (or muscular dystrophies) are a subgroup of myopathies

characterized by muscle degeneration and regeneration. Clinically, muscular
dystrophies are typically progressive, because the muscles' ability to regenerate is
eventually lost, leading to progressive weakness, often leading to use of
a wheelchair, and eventually death, usually related to respiratory weakness.
(G71.1) Myotonia
Neuromyotonia
(G71.2) The congenital myopathies do not show evidence for either a
progressive dystrophic process (i.e., muscle death) or inflammation, but instead

characteristic microscopic changes are seen in association with reduced contractile
ability of the muscles. Congenital myopathies include, but are not limited to:
(G71.2) nemaline myopathy (characterized by presence of "nemaline

rods" in the muscle),
Myopathy in systemic diseases

Myopathies in systemic disease results from several different disease processes
including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced,
(G71.2) multi/minicore myopathy (characterized by multiple small "cores"

or areas of disruption in the muscle fibers),
(G71.2) centronuclear myopathy (or myotubular myopathy) (in which
Dermatomyositis produces muscle weakness and skin changes. The skin
the nuclei are abnormally found in the center of the muscle fibers), a rare
rash is reddish and most commonly occurs on the face, especially around the
muscle wasting disorder
eyes, and over the knuckles and elbows. Ragged nail folds with visible
capillaries can be present. It can often be treated by drugs like corticosteroids or
(G71.3) Mitochondrial myopathies, which are due to defects in mitochondria,
immunosuppressants. (M33.2)
which provide a critical source of energy for muscle
(G72.3) Familial periodic paralysis
(G72.4) Inflammatory myopathies, which are caused by problems with the
Polymyositis produces muscle weaknesss. It can often be treated by

drugs like corticosteroids or immunosuppressants.
Inclusion body myositis is a slowly progressive disease that produces
immune system attacking components of the muscle, leading to signs
weakness of hand grip and straightening of the knees. No effective treatment is
of inflammation in the muscle
known.
(G73.6) Metabolic myopathies, which result from defects in biochemical
(M61) Myositis ossificans
(M62.89) Rhabdomyolysis and (R82.1) myoglobinurias
metabolism that primarily affect muscle
(G73.6/E74.0) Glycogen storage diseases, which may affect muscle
(G73.6/E75) Lipid storage disorder
The Food and Drug Administration is recommending that physicians restrict prescribing
Acquired
high-dose Simvastatin (Zocor, Merck) to patients, given an increased risk of muscle

damage. The FDA drug safety communication stated that physicians should limit using
the 80-mg dose unless the patient has already been taking the drug for 12 months and
(G72.0 - G72.2) External substance induced myopathy
there is no evidence of myopathy. "Simvastatin 80 mg should not be started in new

patients, including patients already taking lower doses of the drug," the agency states.
(G72.0) Drug-induced myopathy
Glucocorticoid myopathy is caused by this class of

steroids increasing the breakdown of the muscle proteins leading to muscle
atrophy.[5]
(G72.1) Alcoholic myopathy
(G72.2) Myopathy due to other toxic agents

(M33.0-M33.1)
Differential diagnosis of systemic myopathy based on age of

onset
Myopathies presenting at birth:- None as systemic causes; mainly hereditary
Myopathies presenting in childhood:Inflammatory myopathies dermatomyositis, polymyositis (rarely)
Infectious myopathies
Endocrine and metabolic disorders hypokalemia, hypocalcemia, hypercalcemia
Clinical features
Myopathies presenting in adulthood
The incidence of this disease is not precisely known but it is considered to be rare (<
1/106 population). It has been reported in 15 families to date mostly
Inflammatory myopathies polymyositis, dermatomyositis, inclusion body myositis, viral
from Canada, Finlandand France.
(HIV)
This disease usually presents between the ages of 5 to 10 years old. The usual picture is
Infectious myopathies
with weakness involving the upper legs and affects activities such as running and
climbing stairs. As the condition progresses, patients tend to experience weakness in
Endocrine myopathies thyroid, parathyroid, adrenal, pituitary disorders

Toxic myopathies alcohol, corticosteroids, narcotics, colchicines, chloroquine
Critical illness myopathy
Metabolic myopathies
Paraneoplastic myopathy
Symptoms
Common muscle weakness. Also (R25.2) cramps (M25.6) stiffness, and

(R29.0) tetany
their lower legs and arms. Some remain able to walk in advanced age, while others
require assistance in adulthood.
Investigations
The serum creatinine is raised.
Acid maltase deficiency
Danon disease
Diagnosis
The diagnosis can be established by muscle biopsy.
Genetics
Myopathy, X-linked, with excessive

autophagy
X-linked myopathy with excessive autophagy (XMEA) is a rare childhood onset disease
characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is
no known cardiac or intellectual involvement.
This disorder is inherited in a recessive X linked fashion. As a result males are much
more commonly affected than females.
It is due to a mutation in VMA21 gene - the human homolog of the yeast Vma21p
protein. This gene is located on the long arm of chromosome X (Xq28). It is a is an
essential assembly chaperone of the vacuolar ATPase - the principal mammalian proton
pump complex. Mutations in this gene increase lysosomal pH. This in turn reduces
lysosomal degradative ability and blocks autophagy.
Pathology
The muscle fibers are rarely necrotic but have evidence of excessive autophagic activity
and exocytosis of the phagocytosed material. They have increased variation in size and
are predominantly composed of round small and hypertrophic fibers. The vacuoles are
strongly reactive for dystrophin and lysosome associated membrane protein 2 (LAMP2).
Membrane bound vacuoles and balls of dense material under the basal lamina are
present. Deposition of the C5b-9 complement attack complex,
subsarcolemmal deposition of calcium and expression of MHC1 complex also occur.
On electron microscopy characteristic balls of dense material are commonly seen. The
vacuoles may contain remains of mitochondria, membrane whorls and calcium apatite
Myositis ossificans
crystals.
Myositis
Myositis ossificans comprises two syndromes characterized by heterotopic

ossification (calcification) of muscle.
Classification
Not to be confused with meiosis, miosis, mitosis, or myosotis.
In the first, and by far most common type, nonhereditary myositis
Myositis is a general term for inflammation of the muscles. Many such conditions are
considered likely to be caused by autoimmuneconditions, rather than directly due
to infection[1] (although autoimmune conditions can be activated or exacerbated by
infections.) It is also a documented side effect of the lipid-lowering drugs statins and
fibrates.
ossificans (commonly referred to simply as "myositis ossificans", as in the remainder
Elevation of creatine kinase in blood is indicative of myositis.
of this article), calcifications occur at the site of injured muscle, most commonly in
the arms or in the quadriceps of the thighs.
The term myositis ossificans traumatica is sometimes used when the
condition is due to trauma.[1][2] Also Myositis ossificans circumscripta is another
synonym of myositis ossificans traumatica refers to the new extraosseous bone
that appears after trauma.[3]
The second condition, myositis ossificans progressiva (also referred to

as fibrodysplasia ossificans progressiva) is an inherited affliction, autosomal
dominant pattern, in which the ossification can occur without injury, and typically
grows in a predictable pattern. Although this disorder can be passed to offspring by
those afflicted with FOP, it is also classified as nonhereditary, as it is most often
attributed to a spontaneous genetic mutation upon conception.
Most (i.e. 80%) ossifications arise in the thigh or arm, and are caused by a premature
Radiologic diagnosis
return to activity after an injury. Other sites include intercostal spaces, erector
spinae,pectoralis muscles, glutei, and the chest. On planar x-ray, hazy densities are
The radiological features of myositis ossificans are faint soft tissue calcification within 2
sometimes noted approximately one month after injury, while the denser opacities
6 weeks, (may have well-defined bony margins by 8 weeks) separated from periosteum
eventually seen may not be apparent until two months have passed.
by lucent zone and on CT, the characteristic feature is peripheral ossification
Pathophysiology of myositis ossificans traumatica
Prevention
The specific cause and pathophysiology are unclear - it may be caused by an interaction
Radiation therapy subsequent to the injury or as a preventive measure of recurrence
between local factors (e.g., a reserve of available calcium in adjacent skeletal tissue or
may be applied but its usefulness is inconclusive. [10] if the surgery performed next step in
soft tissue edema, vascular stasis tissue hypoxia or mesenchymal cells with osteoblastic
accordance with literature postoperative single low-dose radiation with 3 weeks of oral
activity) and unknown systemic factors. The basic mechanism is the inappropriate
indomethacin regimen will be preventive for recurrence.
differentiation of fibroblasts into bone-forming cells (osteoblasts). Early edema of

connective tissue proceeds to tissue with foci of calcification and then to maturation of
calcification and osifications
Treatment
Sonographic diagnosis
Treatment is initially conservative, as some patients' calcifications will spontaneously be
Calcification is typically depicted 2 weeks earlier at US when compared to radiographs.

[4]
The lesion develops in two distinct stages with different presentations at US. [5] In the
early stage, termed immature, it is depicts a non-specific soft tissue mass that ranges
from a hypoechoic area with an outer sheet-like hyperechoic peripheral rim to a highly
echogenic area with variable shadowing. In the late stage, termed mature, myositis
ossificans is depicted as an elongated calcific deposit that is aligned with the long-axis of
reabsorbed, and others will have minimal symptoms. In occasional cases,

surgicaldebridement of the abnormal tissue is required, although success of such
therapy is limited.
Treatment of myositis ossificans:
Rest
Reduction
changes before they become pathognomonic.
Immobilization
The differential diagnosis includes many tumoral and nontumoral pathologies. A main
Anti-inflammatory drugs
Physiotherapy management
the muscle, exhibits acoustic shadowing, and has no soft tissue mass associated. US
may suggest the diagnosis at early stage, but imaging features need to evolve with
successive maturation of the lesion and formation of the characteristic late stage
concern is to differentiate early myositis ossificans from malignant soft-tissue tumors,

and the latter is suggested by a fast-growing process. If clinical or sonographic findings
are dubious and extraosseous sarcoma is suspected, biopsy should be performed. At
histology, detection of the typical zonal phenomenon is diagnostic of myositis ossificans,
Surgical removal of the myositis ossificans is rarely warranted. If the myositis ossificans
though microscopic findings may be misleading during the early stage.
is excised before its maturation, it will likely reoccur. Consequently, most healthcare
[6]
providers wait 612 months before considering excision. There is a chance of relapse
even when removed in a mature state. In general, myositis ossificans is removed

surgically if it limits the range of motion of the joint, irritates a nerve or lowers quality of
People with a mutation in one copy of the MSTN gene in each cell (heterozygotes) also
have increased muscle bulk, but to a lesser degree.
life.
Orofacial myological disorders

Orofacial myofunctional disorders (OMD) (sometimes called oral myofunctional

disorder", and tongue thrust) are muscle disorders of the face, mouth, lips, or jaw.
Recent studies on incidence and prevalence of tongue thrust behaviors are not available.
However, according to the previous research, 38% of various populations have OMD.
The incidence is as high as 81% in children exhibiting speech/articulation problems
(Kellum, 1992).
Indications
OMD refers to abnormal resting posture of the orofacial musculature, atypical chewing,
and swallowing patterns, dental malocclusions, blocked nasal airways, and speech
problems.[1] OMD are patterns involving oral and/orofacial musculature that interferes
with normal growth, development, or function of structures, or calls attention to itself.
OMD are found in both children and adults. OMD that are commonly seen in children
include tongue thrust that is also known as swallowing with an anterior tongue posture.
Myostatin-related muscle hypertrophy
OMD also refers to factors such as nonnutritive sucking behaviors, such as thumb
sucking, clenching, bruxing, etc. that lead to abnormal development of dentition and oral
cavity. OMD in adult and geriatric population are due to various neurological
Myostatin-related muscle hypertrophy (or myotonic hypertrophy) is a rare genetic

condition characterized by reduced body fat and increased skeletal muscle size. Affected
individuals have up to twice the usual amount of muscle mass in their bodies. They also
tend to have increased muscle strength. Myostatin-related muscle hypertrophy is not
known to cause any medical problems, and affected individuals are intellectually normal.
The prevalence of this condition is unknown.
impairments, oral hygiene, altered functioning of muscles due to aging, systemic
Mutations in the MSTN gene cause myostatin-related muscle hypertrophy.

The MSTN gene provides instructions for making a protein called myostatin, which is
active in muscles used for movement (skeletal muscles) both before and after birth. This
protein normally restrains muscle growth, ensuring that muscles do not grow too large.
Mutations that reduce the production of functional myostatin lead to an overgrowth of
muscle tissue. Myostatin-related muscle hypertrophy has a pattern of inheritance known
as incomplete autosomal dominance. People with a mutation in both copies of the MSTN
gene in each cell (homozygotes) have significantly increased muscle mass and strength.
teeth while swallowing, chewing, resting, or speaking. Abnormal swallowing patterns
diseases, etc.
Tongue thrusting is a type of orofacial myofunctional disorder, which is defined as
habitual resting or thrusting the tongue forward and/or sideways against or between the
push the upper teeth forward and away from the upper alveolar processes and cause
open bites. In children, tongue thrusting is common due to immature oral behavior,
narrow dental arch, prolonged upper respiratory tract infections, spaces between the
teeth (diastema), muscle weakness, malocclusion, abnormal sucking habits, and open
mouth posture due to structural abnormalities of genetic origin. Large tonsils and
5. Inadequate development of facial and cranial bones
adenoids also contribute totongue thrust swallowing.

6. Inappropriate development of muscles in the head and neck areas
From the dental perspective, teeth move in relation to the balance of the soft tissue; the
normal relationship of teeth lies in occlusion; and any deviation from the normal
While identifying the causes of tongue thrust, it is important to remember that the resting
occlusion can lead to dental distress.[2] Tongue posture plays an important role in
posture of the tongue, jaw, and lips are crucial to normal development of mouth and its
swallowing and dentofacial growth. In case of tongue thrust swallowing, the tip of the
structures. If tongue rests against the upper front teeth, the teeth may protrude forward,
tongue can come against or between the dentition; the midpoint may be collapsed or
and adverse tongue pressure can restrict the development of the oral cavity. The tongue
extended unilaterally or bilaterally; or the posterior part of the hard palate. In these
lies low in the mouth or oral cavity and is typically forwarded between upper and lower
conditions, there are chances of abnormal dentofacial growth and other concerns
teeth. If tongue thrust behavior is not corrected, it may affect the normal dental
regarding development of the craniofacial complex.
development. The teeth may be pushed around in different directions during the growth
of permanent teeth.
There are pertinent symptomatic questions that can be considered for the diagnosis of
tongue thrust swallow. Some of these questions are geared toward tongue protrusion
Consequences of tongue thrust
and an opening of lips when the client is in repose; habitual mouth breathing; digit
sucking; existence of high and narrow palatal arch; ankyloglossia (tongue-
1. Lisping (e.g., saying thun for sun)
tie); malocclusions, (Class II, III); weak chewing muscles (masseter); weak lip muscles
(orbicularis oris); overdeveloped chin muscles (mentalis); muscular imbalance; abnormal
2. Imprecise articulation of speech sounds
dentition.
3. Open-mouth posture
Tongue thrusting and speech problems may co-occur. Due to unconventional postures of
the tongue and other articulators, interdental and frontal lisping are very common. The
4. Open bite
alveolar sounds /s/ and /z/ are produced more anteriorly thus leading to interdental
fricative like sounds, /th/.[3]
5. Abnormal eruption of teeth and dental arch
Causes
6. Abnormal tone of facial muscles
1. Upper airway constrictions (e.g., deviated nasal septum) or obstructions (e.g.,
7. Prolonged meal times due to ineffective chewing and swallowing
enlarged tonsils) or infections (e.g., rhinitis)

8. Spillage of food/fluid from the anterior mouth
2. General hypotonia or low body tone
9. Negative cosmetic effects
3. Low-lying resting posture of the tongue
10.Lower self-esteem
4. Imbalance in dental growth
11. Problems with fitting of denture in future
Open mouth posture

The adaptation from nasal to mouth breathing takes pace when changes such as chronic
middle ear infections, sinusitis, allergic rhinitis, upper airway infections, and sleep
disturbances (e.g., snoring) take place. In addition, mouth breathing is often associated
with a decrease in oxygen intake into the lungs. Mouth breathing can particularly affect
3. Retrain oral, lingual, and facial muscles to facilitate correct resting posture of
tongue, lips, and jaw
4. Establish mature swallowing patterns
5. Prevent relapses after orthodontic treatment
the growing face, as the abnormal pull of these muscle groups on facial bones slowly
deforms these bones, causing misalignment. The earlier in life these changes take place,
6. Improve relationship between dental arches; reduce open bite and overjet
the greater the alterations in facial growth, and ultimately an open mouth posture is
created where the upper lip is raised and the lower jaw is maintained in an open posture.
7. Improve nasal breathing patterns
The tongue, which is normally tucked under the roof of the mouth, drops to the floor of
the mouth and protrudes to allow a greater volume of air intake. Consequently, an open
8. Maintain overall facial muscle tone needed for chewing, swallowing, and speech
mouth posture can lead to malocclusions and problems in swallowing. Other causes of
open-mouth posture are weakness of lip muscles, overall lack of tone in the body or
hypotonia, and prolonged/chronic allergies of the respiratory tract. A.union
Therapy
Also called myofunctional therapy, the basic treatment aims of orofacial myofunctional
therapist is to reeducate the movement of muscles, restore correct swallowing patterns,
and establish adequate labial-lingual postures.[2][4][5] An interdisciplinary nature of
treatment is always desirable to reach functional goals in terms of swallowing, speech,
and other esthetic factors. A team approach has been shown to be effective in correcting
orofacial myofunctional disorders. The teams include an orthodontist, dental hygienist,
certified orofacial myologist, general dentist, otorhinolaryngologist, and a speechlanguage pathologist.
Goals/benefits of therapy
1. Reinforce and establish a resting posture of the tongue away from the teeth,
against the hard palate
2. Establish appropriate oral, lingual, and facial muscle patterns that promote
correct gestures for chewing and eating
9. Create an oral environment that creates favorable conditions for development of

dentition
10.Eliminate open-mouth posture
11. Eliminate dry mouth condition or xerostomia
12.Improve oral hygiene
13.Eliminate digit-sucking behaviors to facilitate normal growth of the palatal arch
Psoas muscle abscess

Owing to the proximal attachments of the iliopsoas, a pus-filled abscess (psoas
abscess), as may occur in lumbar tuberculosis, may drain inferiorly into the upper medial
thigh and present as a swelling in the region.
Treatment may involve drainage and antibiotics.
Pelvic floor muscle disorder
Paratonia
In pelvic floor muscle disorder the muscles of the pelvic floor remain tightened.
Normally these muscles are under voluntary control, but for some excessive tension can
develop. Reasons for this are not well known but can be resultant from a natural
disposition, learned reaction to stress or pain, trauma, or any combination of these.
Excessive pelvic floor tension can result in various problems including frequent urination
(due to the bladder's inability to expand) or pain. Treatments involve relaxing the
muscles, using medication (such as tamsulosin), biofeedback, or physical therapy.
Paratonia or gegenhalten is defined as "a form of hypertonia with an involuntary

variable resistance during passive movement."[1] In other words, attempting to move the
limb of a person with paratonia will result in that person involuntarily resisting the
movement. The amount of resistance is determined by the speed of the movement:
faster, more forceful movements will result in greater amounts of resistance. [1] It is also
present regardless of the direction of the movement.[1]
Paratonia can be distinguished from spasticity by observing a lack of exaggerated deep
tendon reflexes and a lack of a clasp-knife response.[1] It can be distinguished from
Parkinsonian (aka "lead-pipe") rigidity in that the amount of resistance in Parkinsonian
rigidity does not vary with the velocity of the movement.[1]
Paratonia develops during a period of dementia and the degree of effect is dependent
upon the disease's progress.[1]
Paratonia was classified very recently by experts, and is unrelated to the much more
typical spasticity associated with spastic diplegia and similar forms of cerebral palsy. also
in frontal lobe stroke.
Pyomyositis
Pyomyositis, also known as tropical pyomyositis or myositis tropicans, is
a bacterial infection of the skeletal muscles which results in a pus-filled abscess.
Pyomyositis is most common in tropical areas but can also occur in temperate zones.
Epidemiology
Pyomyositis is most often caused by the bacterium Staphylococcus aureus.[1] The
infection can affect any skeletal muscle, but most often infects the large muscle groups
such as the quadriceps or gluteal muscles.[2][3][4]
Pyomyositis is mainly a disease of children and was first described by Scriba in 1885.
Most patients are aged 2 to 5 years, but infection may occur in any age group. [5]
[6]
Infection often follows minor trauma and is more common in the tropics, where it
accounts for 4% of all hospital admissions. In temperate countries such as the US,
pyomyositis was a rare condition (accounting for 1 in 3000 pediatric admissions), but has
become more common since the appearance of the USA300 strain of MRSA.[2][3][4]
Treatment
The abscesses within the muscle must be drained surgically (not all patient require
surgery if there is no abscess). Antibiotics are given for a minimum of three weeks to
clear the infection.
Strain (injury)
A strain is an injury to a muscle in which the muscle fibers tear as a result

of overstretching. A strain is also colloquially known as apulled muscle. The equivalent
injury to a ligament is a sprain.
Sarcoglycanopathy
Symptoms
Typical symptoms of a strain include localized stiffness, discoloration
The sarcoglycanopathies are a collection of diseases resulting from mutations in any of

the four sarcoglycan genes: , , or . The four sarcoglycanopathies are: sarcoglycanopathy, LGMD2D; -sarcoglycanopathy, LGMD2E; -sarcoglycanopathy,
LGMD2C and -sarcoglycanopathy, LGMD2F. The four different sarcoglycan genes
encode proteins that form a tetrameric complex at the muscle cell plasma membrane.
This complex stabilizes the association of dystrophin with the dystroglycans and
contributes to the stability of the plasma membrane cytoskeleton. The four sarcoglycan
genes are related to each other structurally and functionally, but each has a
distinct chromosome location.
In outbred populations, the relative frequency of mutations in the four genes is alpha >>
beta >> gamma >> delta in an 8:4:2:1 ratio. No common mutations have been identified
in outbred populations except the R77C mutation, which accounts for up to one-third of
the mutated SGCA alleles. Founder mutations have been observed in certain
populations.[1]A 1997 Italian clinical study demonstrated variations in muscular
dystrophy progression dependent on the sarcoglycan gene affected.
and bruising around the strained muscle.
Causes
Strains are a result of muscular-fiber tears due to over stretching; they are very painful.
Although strains are not restricted to athletes and can happen while doing everyday
tasks, people who play sports are more at risk of developing a strain.
Treatment
The first-line treatment for a muscular strain in the acute phase include five steps
commonly known as P.R.I.C.E.[2][3]
Protection: Apply soft padding to minimize impact with objects.
Rest: Rest is necessary to accelerate healing and reduce the potential for
reinjury.
Sphincter paralysis
ice for more than 20 minutes at a time.
Sphincter paralysis is paralysis of one of the body's many sphincters, preventing it from
constricting normally.
Case studies have shown patients may remain continent for many years despite being
affected by anal sphincter paralysis.
Ice: Apply ice to reduce swelling by reducing blood flow to the injury site. Never
Compression: Wrap the strained area to reduce swelling with a soft-wrapped

bandage.
Elevation: Keep the strained area as close to the level of the heart as is
conveniently possible to keep blood from pooling in the injured area.
The ice and compression (cold compression therapy) will stop the pain and swelling
while the injury starts to heal itself. Controlling the inflammation is critical to the healing
process, and the icing further restricts fluid leaking into the injured area as well as
controlling pain.
Cold compression therapy wraps are a useful way to combine icing and compression to
stop swelling and pain.
This immediate treatment is usually accompanied by the use of nonsteroidal antiinflammatory drugs[4] (e.g., ibuprofen), which both reduce the immediate inflammation
and relieve pain. However, NSAIDs, including aspirin and ibuprofen, affect platelet
function (this is why they are known as "blood thinners") and should not be taken during
the period when tissue is bleeding because they will tend to increase blood flow, inhibit
clotting, and thereby increase bleeding and swelling. After the bleeding has stopped,
NSAIDs can be used with some effectiveness to reduce inflammation and pain.
It is recommended[5] that the person injured should consult a medical provider if the injury
Thyrotoxic periodic paralysis

Thyrotoxic periodic paralysis (TPP) is a condition featuring attacks of muscle

weakness in the presence of hyperthyroidism(overactivity of
the thyroid gland). Hypokalemia (a decreased potassium level in the blood) is usually
present during attacks. The condition may be life-threatening if weakness of
the breathing muscles leads to respiratory failure, or if the low potassium levels lead
to cardiac arrhythmias (irregularities in the heart rate).[1][2] If untreated, it is typically
recurrent in nature.[1]
The condition has been linked with genetic mutations in genes that code for certain ion
channels that transport electrolytes (sodiumand potassium) across cell membranes. The
main ones are the L-type calcium channel 1-subunit[1] and potassium inward rectifier
2.6;[3] it is therefore classified as a channelopathy.[3] The abnormality in the channel is
thought to lead to shifts of potassium intocells, under conditions of high thyroxine (thyroid
hormone) levels, usually with an additional precipitant.
a sprain, or a complete muscle tear.
Treatment of the hypokalemia, followed by correction of the hyperthyroidism, leads to

complete resolution of the attacks. It occurs predominantly in males of Chinese,
Japanese, Vietnamese, Filipino, and Korean descent.[1] TPP is one of several conditions
that can cause periodic paralysis.
Therapeutic ultrasound can be used to break down poorly healed muscle strains and
Signs and symptoms
is accompanied by severe pain, if the limb cannot be used, or if there is noticeable

tenderness over an isolated spot. These can be signs of a broken or fractured bone,
permit them to heal properly.

An attack often begins with muscle pain, cramping, and stiffness. [5] This is followed by
weakness or paralysis that tends to develop rapidly, usually in late evening or the early
hours of the morning. The weakness is usually symmetrical;[5] the limb muscles closer to
the trunk (proximal) are predominantly affected, and weakness tends to start in the legs
and spread to the arms. Muscles of the mouth and throat, eyes, and breathing are
usually not affected, but occasionally weakness of the respiratory muscles can cause
life-threatening respiratory failure. Attacks typically resolve within several hours to
several days, even in the absence of treatment.[1][2][5] On neurological examination during
an attack,flaccid weakness of the limbs is noted; reflexes are usually diminished, but
the sensory system is unaffected.[1][5] Mental status is not affected.[5]
Attacks may be brought on by physical exertion, drinking alcohol, or eating food high
in carbohydrates or salt. This may explain why attacks are more common in summer,
when more people drink sugary drinks and engage in exercise. Exercise-related attacks
Thyroid disease
tend to occur during a period of rest immediately after exercise; exercise may therefore
be recommended to abort an attack.[1]
The most common underlying form of thyroid disease associated with TPP is Graves'
disease, a syndrome due to an autoimmune reaction that leads to overproduction of
There may be symptoms of thyroid overactivity, such as weight loss, a fast heart
thyroid hormone.[6] TPP has also been described in people with other thyroid problems
rate, tremor, and perspiration;[1][2] but such symptoms occur in only half of all cases.[5] The
such as thyroiditis, toxic nodular goiter, toxic adenoma, TSH-producing pituitary
most common type of hyperthyroidism, Graves' disease, may additionally cause eye
adenoma, excessive ingestion of thyroxine or iodine,[1] and amiodarone-induced
problems (Graves' ophthalmopathy) and skin changes of the legs (pretibial myxedema).
hyperthyroidism.[2]
[6]
Thyroid disease may also cause muscle weakness in the form of thyrotoxic myopathy,
but this is constant rather than episodic.[5]
Mechanism
Causes
Genetics
Genetic mutations in the L-type calcium channel 1-subunit (Ca v1.1) have been
described in Southern Chinese with TPP. The mutations are located in a different part of
the gene from those described in the related condition familial periodic paralysis. In TPP,
the mutations described are single-nucleotide polymorphisms located in the hormone
response element responsive to thyroid hormone, implying that transcription of the gene
and production of ion channels may be altered by increased thyroid hormone levels.
Furthermore, mutations have been reported in the genes coding for potassium voltagegated channel, Shaw-related subfamily, member 4 (Kv3.4) and sodium channel protein
type 4 subunit alpha (Na41.4).[1]
Of people with TPP, 33% from various populations were demonstrated to have mutations
in KCNJ18, the gene coding for Kir2.6, an inward-rectifier potassium ion channel. This
gene, too, harbors a thyroid response element.[3]
Na+/K+-ATPase maintains the normal gradients of sodium and potassium between cells and extracellular
fluid, expending the cellular fuel ATP in doing so.
The muscle weakness and increased risk of irregular heart beat in TPP result from
markedly reduced levels of potassium in the bloodstream. Potassium is not in fact lost
from the body, but increased Na+/K+-ATPase activity (the enzyme that moves potassium
into cells and keepssodium in the blood) leads to shift of potassium into tissues, and
Certain forms of human leukocyte antigen (HLA)especially B46, DR9, DQB1*0303, A2,
depletes the circulation. In other types of potassium derangement, the acid-base
Bw22, AW19, B17, and DRW8are more common in TPP. Linkage to particular forms of
balance is usually disturbed, withmetabolic alkalosis and metabolic acidosis often being
HLA, which plays a central role in the immune response, might imply an immune system
present. In TPP, these disturbances are generally absent. Hypokalemia leads
cause, but it is uncertain whether this directly causes TPP or whether it increases the
to hyperpolarization of muscle cells, making theneuromuscular junction less responsive
susceptibility to Graves' disease, a known autoimmune disease.[1]
to normal nerve impulses and leading to decreased contractility of the muscles. [1]
It is not clear how the described genetic defects increase the Na +/K+-ATPase activity, but
it is suspected that the enzyme becomes more active due to increased thyroid hormone
levels. Hyperthyroidism increases the levels of catecholamines (such as adrenaline) in
the blood, increasing Na+/K+-ATPase activity.[5] The enzyme activity is then increased
potassium in the body is not decreased, and it is possible for potassium levels to
further by the precipitating causes. For instance, increased carbohydrate intake leads to
overshoot ("rebound hyperkalemia"); slow infusions of potassium chloride are therefore
increased insulin levels; this is known to activate Na+/K+-ATPase. Once the precipitant is
recommended while other treatment is commenced.[1]
removed, the enzyme activity returns to normal levels.[1] It has been postulated that male
hormones increase Na+/K+-ATPase activity, and that this explains why males are at a
The effects of excess thyroid hormone typically respond to the administration of a non-
higher risk of TPP despite thyroid disease being more common in females.[2]
selective beta blocker, such as propranolol (as most of the symptoms are driven by
increased levels of adrenaline and its effect on the -adrenergic receptors). Subsequent
TPP is regarded as a model for related conditions, known as "channelopathies", which
attacks may be prevented by avoiding known precipitants, such as high salt or
have been linked with mutations in ion channels; the majority of these conditions occurs
carbohydrate intake, until the thyroid disease has been adequately treated. [1]
episodically.[3]
Treatment of the thyroid disease usually leads to resolution of the paralytic attacks.
Diagnosis
Depending on the nature of the disease, the treatment may consist of thyrostatics (drugs
that reduce production of thyroid hormone), radioiodine, or occasionally thyroid surgery.
Hypokalaemia (low blood potassium levels) commonly occurs during attacks; levels
below 3.0 mmol/l are typically encountered. Magnesium and phosphate levels are often
Epidemiology
found to be decreased. Creatine kinase levels are elevated in two thirds of cases, usually
due to a degree of muscle injury; severe elevations suggestive
TPP occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and
of rhabdomyolysis (muscle tissue destruction) are rare.[1]
Korean descent,[1] as well as Thais,[3] with much lower rates in people of other ethnicities.
[2]
Electrocardiography (ECG/EKG) may show tachycardia (a fast heart rate) due to the
[1]
In Chinese and Japanese people with hyperthyroidism, 1.81.9% experience TPP. This
thyroid disease, abnormalities due to cardiac arrhythmia (atrial fibrillation, ventricular
is in contrast to North America, where studies report a rate of 0.10.2%. [1][2] Native
tachycardia), and conduction changes associated with hypokalemia (U waves, QRS
Americans, who share a genetic background with East Asians, are at an increased risk. [1]
widening, QT prolongation, and T wave flattening).[2]Electromyography shows changes

similar to those encountered in myopathies (muscle diseases), with a reduced amplitude
of the compound muscle action potentials (CMAPs);[4]they resolve when treatment has
commenced.[1]
The typical age of onset is 2040. It is unknown why males are predominantly affected,
with rates in males being 17- to 70-fold those in females, despite thyroid overactivity
being much more common in women.
TPP is distinguished from other forms of periodic paralysis (especially hypokalemic

periodic paralysis) with thyroid function tests on the blood. These are normal in the other
forms, and in thyrotoxicosis the levels of thyroxine and triiodothyronine are elevated, with
resultant suppression of TSH production by the pituitary gland.[1][6] Various other
investigations are usually performed to separate the different causes of hyperthyroidism.
[6]
Treatment
In the acute phase of an attack, administration of potassium will quickly restore muscle
strength and prevent complications. However, caution is advised as the total amount of
Weakness
This article is about the medical condition. For other uses, see Weakness
(disambiguation).
Weakness or asthenia is a symptom of a number of different conditions.[1] The
causes are many and can be divided into conditions that have true or perceived
muscle weakness. True muscle weakness is a primary symptom of a variety
of skeletal muscle diseases, including muscular dystrophy and inflammatory

myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis.
Myasthenia (my- from Greek meaning "muscle" + -asthenia meaning

"weakness"), or simply muscle weakness, is a lack of muscle strength. The causes are
Diagnostic Distinctions
many and can be divided into conditions that have either true or perceived muscle
True weakness vs. perceived weakness
weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle
in neuromuscular diseases, such as myasthenia gravis.
True weakness (or neuromuscular) describes a condition where the force

exerted by the muscles is less than would be expected, for example muscular
diseases, including muscular dystrophy and inflammatory myopathy. It occurs
dystrophy.
Muscle fatigue can be central, neuromuscular, or peripheral muscular. Central muscle
Perceived weakness (or non-neuromuscular) describes a condition where a
fatigue manifests as an overall sense of energy deprivation, and peripheral muscle
person feels more effort than normal is required to exert a given amount of force but
weakness manifests as a local, muscle-specific inability to do work.[10][11] Neuromuscular
actual muscle strength is normal, for example chronic fatigue syndrome.[2]
fatigue can be either central or peripheral.
In some conditions, such as myasthenia gravis, muscle strength is normal when resting,
Central fatigue
but true weakness occurs after the muscle has been subjected to exercise. This is also
true for some cases of chronic fatigue syndrome, where objective post-exertion muscle
The central fatigue is generally described in terms of a reduction in the neural drive or
weakness with delayed recovery time has been measured and is a feature of some of
nerve-based motor command to working muscles that results in a decline in the force
the published definitions.
output. It has been suggested that the reduced neural drive during exercise may be a
protective mechanism to prevent organ failure if the work was continued at the same
Asthenia vs. myasthenia
intensity.[15][16] The exact mechanisms of central fatigue are unknown, though there has
been a great deal of interest in the role of serotonergic pathways.
Asthenia (Greek: , lit. lack of strength but also disease) is a medical term
referring to a condition in which the body lacks or has lost strength either as a whole or in
Neuromuscular fatigue
any of its parts. It denotes symptoms of physical weakness and loss of strength. General
asthenia occurs in many chronic wasting diseases (such as tuberculosis and cancer),
Nerves control the contraction of muscles by determining the number, sequence, and
sleep disorders or chronic disorders of the heart, lungs or kidneys, and is probably most
force of muscular contraction. When a nerve experiences synaptic fatigue it becomes
marked in diseases of the adrenal gland. Asthenia may be limited to certain organs or
unable to stimulate the muscle that it innervates. Most movements require a force far
systems of organs, as in asthenopia, characterized by ready fatiguability. Asthenia is also
below what a muscle could potentially generate, and barring pathology, neuromuscular
a side effect of some medications and treatments, such as Ritonavir (a protease
fatigue is seldom an issue.
inhibitor used inHIV treatment), vaccines such as the HPV

vaccine Gardasil[9] and fentanyl patches (an opioid used to treat pain).
For extremely powerful contractions that are close to the upper limit of a muscle's ability
to generate force, neuromuscular fatigue can become a limiting factor in untrained
Differentiating psychogenic (perceived) asthenia and true asthenia from myasthenia is
individuals. In novice strength trainers, the muscle's ability to generate force is most
often difficult, and in time apparent psychogenic asthenia accompanying many chronic
strongly limited by nerves ability to sustain a high-frequency signal. After an extended
disorders is seen to progress into a primary weakness.
muscle appears to simply stop listening and gradually cease to move, often lengthening.
Though not universally used, "metabolic fatigue" is a common alternative term for
As there is insufficient stress on the muscles and tendons, there will often be no delayed
peripheral muscle weakness, because of the reduction in contractile force due to the
onset muscle soreness following the workout. Part of the process of strength training is
direct or indirect effects of the reduction of substrates or accumulation of metabolites
increasing the nerve's ability to generate sustained, high frequency signals which allow a
within the myocytes. This can occur through a simple lack of energy to fuel contraction,
muscle to contract with their greatest force. It is this "neural training" that causes several
or through interference with the ability of Ca2+ to stimulate actin and myosin to contract.
weeks worth of rapid gains in strength, which level off once the nerve is generating
maximum contractions and the muscle reaches its physiological limit. Past this point,
training effects increase muscular strength through myofibrillar or
force.
Lactic acid hypothesis

It was once believed that lactic acid build-up was the cause of muscle fatigue.[21] The
Peripheral muscle fatigue
Peripheral muscle fatigue during physical work is considered[by whom?] an inability for the
body to supply sufficient energy or other metabolites to the contracting muscles to meet
muscles. This can lower the sensitivity of contractile apparatus to calcium ions (Ca2+) but
the increased energy demand. This is the most common case of physical fatigue
also has the effect of increasing cytoplasmic Ca2+ concentration through an inhibition of
affecting a national[where?] average of 72% of adults in the work force in 2002. This causes
the chemical pump that actively transports calcium out of the cell. This counters inhibiting
contractile dysfunction that manifests in the eventual reduction or lack of ability of a
effects of potassium ions (K+) on muscular action potentials. Lactic acid also has a
single muscle or local group of muscles to do work. The insufficiency of energy, i.e. sub-
negating effect on the chloride ions in the muscles, reducing their inhibition of contraction
optimal aerobic metabolism, generally results in the accumulation of lactic acid and
and leaving K+ as the only restricting influence on muscle contractions, though the effects
other acidic anaerobic metabolic by-products in the muscle, causing the stereotypical
of potassium are much less than if there were no lactic acid to remove the chloride ions.
burning sensation of local muscle fatigue, though recent studies have indicated
Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular
otherwise, actually finding that lactic acid is a source of energy.[20]
calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca 2+.
The fundamental difference between the peripheral and central theories of muscle
Pathophysiology
fatigue is that the peripheral model of muscle fatigue assumes failure at one or more
Main article: muscle contraction
sites in the chain that initiates muscle contraction. Peripheral regulation therefore
depends on the localized metabolic chemical conditions of the local muscle affected,
Muscle cells work by detecting a flow of electrical impulses from the brain, which signals
whereas the central model of muscle fatigue is an integrated mechanism that works to
preserve the integrity of the system by initiating muscle fatigue through muscle
derecruitment, based on collective feedback from the periphery, before cellular or organ
themselves. New research from scientists at Columbia University suggests that muscle
failure occurs. Therefore the feedback that is read by this central regulator could include
fatigue is caused by calcium leaking out of the muscle cell. This makes less calcium
chemical and mechanical as well as cognitive cues. The significance of each of these
available for the muscle cell. In addition, the Columbia researchers propose that an
factors will depend on the nature of the fatigue-inducing work that is being performed.
enzyme activated by this released calcium eats away at muscle fibers.[22]
exhausted, producing lactic acid as a metabolic byproduct. Contrary to common belief,
lactic acid accumulation doesn't actually cause the burning sensation we feel when we
exhaust our oxygen and oxidative metabolism, but in actuality, lactic acid in presence of
oxygen recycles to produce pyruvate in the liver, which is known as the Cori cycle.
Substrates produce metabolic fatigue by being depleted during exercise, resulting in a
lack of intracellular energy sources to fuel contractions. In essence, the muscle stops
contracting because it lacks the energy to do so.
cramp is a task-specific focal dystonia of the hand.[3] 'Focal' refers to the symptoms being
limited to one location (the hand in this case), and 'task-specific' means that symptoms
first occur only when the individual engages in a particular activity. Writer's cramp first
affects an individual by interfering with their ability to write, especially for prolonged
periods of time.
Causes
Although the etiology of writer's cramp is not well known, it was historically believed to be
the result of excessive fine motor activity, possibly complicated by a tense or otherwise
inappropriate writing technique.[4] More recently, Karin Rosenkranz et al. have suggested
that this is not necessarily the case.[5] Musician's cramp (a similar focal dystonia which
affects some 1% of instrumentalists[6]) has historically been grouped together with writer's
cramp because of this and their common task-specificity. Rosenkranz et al. have more
recently identified significant differences between the two populations, however.[5] No
matter exactly how it arises, researchers generally agree that these types of focal
dystonia are the result of a basal ganglia and/or sensorimotor cortex malfunction in the
brain.
Early symptoms may include loss of precision muscle coordination (sometimes first
manifested in declining penmanship, frequent small injuries to the hands, dropped items
and a noticeable increase in dropped or chipped dishes), cramping pain with sustained
use and trembling. Significant muscle pain and cramping may result from very minor
exertions like holding a book and turning pages. It may become difficult to find a
comfortable position for arms and legs with even the minor exertions associated with
holding arms crossed causing significant pain similar to restless leg syndrome. Affected
persons may notice trembling in the diaphragm while breathing, or the need to place
hands in pockets, under legs while sitting or under pillows while sleeping to keep them
still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and
the constant movement to avoid pain may result in the grinding and wearing down of
teeth, or symptoms similar to TMD. The voice may crack frequently or become harsh,
triggering frequent throat clearing. Swallowing can become difficult and accompanied by
Writer's cramp
painful cramping. Patients may also present with varying degree of disability and
symptoms, such as experiencing more difficulty writing down-stroke as compared to
writing upstroke.[2]
Writer's cramp, also called mogigraphia and scrivener's palsy, is a disorder caused
by cramps or spasms of certain muscles of the hand and/or forearm, and presents itself
while performing fine motor tasks, such as writing or playing an instrument. [1][2] Writer's
Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide
stimulation can induce neuroplasticity, making it possible for patients to recover
a definitive diagnosis by showing pulsating nerve signals being transmitted to the
substantial function that was lost from focal dystonia.
muscles even when they are at rest. The brain appears to signal portions of fibers within
the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate,
tremble and contort. When called upon to perform an intentional activity, the muscles
weakness) while other portions over-respond or become rigid (causing micro-tears under
Zenker's degeneration
load). The symptoms worsen significantly with use, especially in the case of focal
fatigue very quickly and some portions of the muscle groups do not respond (causing
dystonia, and a "mirror effect" is often observed in other body parts: use of the right hand
may cause pain and cramping in that hand as well as in the other hand and legs that
were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures
can worsen symptoms.
Direct symptoms may be accompanied by secondary effects of the continuous muscle
and brain activity, including disturbed sleep patterns, exhaustion, mood swings, mental
stress, difficulty concentrating, blurred vision, digestive problems and short temper.
People with dystonia may also become depressed and find great difficulty adapting their
activities and livelihood to a progressing disability. Side effects from treatment and
medications can also present challenges in normal activities.
In some cases, symptoms may progress and then plateau for years, or stop progressing
entirely. The progression may be delayed by treatment or adaptive lifestyle changes,
while forced continued use may make symptoms progress more rapidly. In others, the
symptoms may progress to total disability, making some of the more risky forms of
treatment worth considering in the future.
Treatment
Although dystonias may be induced by chemical exposure/ingestion, brain injury, or
hereditary/genetic predisposition, the task-specific focal dystonias such as writer's cramp
are a unique challenge to diagnose and treat. Some cases may respond to chemical
injections - botulinum toxin (botox) is often cited, though it is not helpful in all cases. [2]
[7]
Behavioral retraining attempts may include writing devices, switching hands, physical
therapy, biofeedback, constraint-induced motion therapy, and others. Some writing

instruments allow variations of pressure application for use. None of these are effective
in all cases, however. The work of Dr. Joaquin Farias has shown that proprioceptive
Zenker's degeneration is a severe glassy or

waxy hyaline degeneration or necrosis of skeletal muscles in acute infectious diseases.
The condition was named by Friedrich Albert von Zenker. It is a hyaline degeneration of
skeletal muscles such as rectus abdominis and diaphragm, and occurs in
severe toxaemiaas typhoid fever. It is also seen in electrical burns. [1] Grossly the muscles
appear pale and friable; microscopically, the muscle fibres are swollen, have a loss of
cross striations, and show a hyaline appearance. Rupture and small hemorrhage may
complicate the lesion. Coagulative necrosis occurs here.

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MUSCULAR SYSTEM DISORDERS

of pericytes due to hyperglycemia, and the reproduction of basement membranes when

Amyotrophy is progressive wasting of muscle tissues. Muscle pain is also a symptom. It

Proximal diabetic neuropathy

ischemia.[7] Experimental treatments using immunosuppressive proteins have provided

From Wikipedia, the free encyclopedia

Proximal diabetic neuropathy, also known as lumbosacral radioplexus

Signs & Symptoms

To definitively diagnose the condition, electrodiagnostic testing can be used. In

addition, needleelectromyography and nerve conduction testing are often used to

Controlling the blood sugar levels

Medication helps reduce the pain involved in proximal diabetic neuropathy.

Length of treatment varies with the amount of nerve damage.[4]

From Wikipedia, the free encyclopedia

Monomelic amyotrophy (MMA), also known as Hirayama disease, Sobue

Anterior compartment syndrome of the

specializing in sports medicine (MD/DO), a doctor of podiatric medicine (DPM), or other

qualified health care professional immediately so as to get the appropriate

advice/treatment before serious damage occurs.

muscles of that compartment: tibialis anterior, extensor hallucis longus, extensor

The 5 Ps of Anterior Compartment Syndrome:

Cataplexy is a sudden and transient episode of muscle weakness accompanied by

Bimagrumab (BYM338) is a human monoclonal antibody developed by Novartis to treat

cause a depletion of the hypocretin neurotransmitter. Secondary cataplexy is associated

Guilleminault et al. investigated 51 prepubertal children with narcolepsy; in 10 subjects (5

of the tumors include astrocytoma, glioblastoma, glioma, and subependynoma. These

missed. Other conditions in which cataplexy can be seen

include ischemic events, multiple sclerosis, head injury,paraneoplastic syndromes, and

significant emotional upset, such as a loss of spouse in older subjects. [11]

Theories for episodes

Medicine" concluded that the neurochemical hypocretin, which is regulated by the

A phenomenon of REM sleep, muscular paralysis, occurs at an inappropriate time. This

cataplexy. Orexin, also known as Hypocretin, is a primary chemical important in

regulating sleep as well as states of arousal. Hypocretin deficiency is further associated

promoting wakefulness, arousal and alertness.[12]

The cholinergic and noradrenergic neurotransmitter systems are targeted in the

the most common presentations. Slurred speech may be present. However,

has been treated with tricyclic antidepressants such

as imipramine, clomipramine or protriptyline. The main feature of tricyclics is their ability

drugs such as venlafaxine.

when patients are deprived of napping while sleepy.[10]

For cataplexy associated with narcolepsy, Xyrem (sodium oxybate) is often

Central core disease of muscle

Emerging therapies include Hypocretin Gene Therapy and Hypocretin Cell

hydroxybutyrate [GHB]), known commercially as Xyrem. Although its mechanism is

The term can be used to refer to cramps in the foot muscles.

Signs and symptoms

Chronic progressive external

Chronic progressive external ophthalmoplegia (CPEO), also known as progressive

Occurring alongside CPEO

Whether a tissue is affected is correlated with the amount of oxidative demands in

Function Index (VF-14).[2]

relation to the amount of mtDNA deletion.

hearing loss, sensory axonal neuropathy, ataxia, clinical depression, hypogonadism,

forms of PEO can be caused by genetic mutations in

the ANT1, POLG, POLG2 and PEO1 genes.

Kearns-Sayre syndrome, is characterized by onset before 15 years of age of CPEO,

heart block and pigmentary retinopathy.

It is important to differentiate CPEO from other pathologies that may cause an

CPEO is diagnosed via muscle biopsy. On examination of muscle fibers stained

critical to the respiratory chain required to produce adenosine triphosphate (ATP).

Deletions or mutations to segments of mtDNA lead to defective function of oxidative