CLINICAL NEUROPHYSIOLOGY

FEVER
Fever, also known as pyrexia and febrile response, is defined as
having a temperature above the normal range due to an increase in
the body's temperature set-point.
There is not a single agreed-upon upper limit for normal
temperature with sources using values between 37.5 and 38.3 °C
(99.5 and 100.9 °F).
The increase in set-point triggers increased muscle contractions and
causes a feeling of cold.
This results in greater heat production and efforts to conserve heat.
When the set-point temperature returns to normal, a person feels
hot, becomes flushed, and may begin to sweat.
Rarely a fever may trigger a febrile seizure. This is more common in
young children.
Fevers do not typically go higher than 41 to 42 °C (105.8 to
107.6 °F).
 FEVER CONT’D
A wide range for normal temperatures has been found.
Central temperatures, such as rectal temperatures, are
more accurate than peripheral temperatures.
Temperature in the anus (rectum/rectal) is at or over
37.5–38.3 °C (99.5–100.9 °F)
Temperature in the mouth (oral) is at or over 37.7 °C
(99.9 °F)
Temperature under the arm (axillary) or in the ear
(tympanic) is at or over 37.2 °C (99.0 °F)
 FEVER CONT’D
In healthy adult men and women, the range of normal,
healthy temperatures for oral temperature is 33.2–
38.2 °C (91.8–100.8 °F), for rectal it is 34.4–37.8 °C
(93.9–100.0 °F), for tympanic membrane (the ear drum)
it is 35.4–37.8 °C (95.7–100.0 °F), and for axillary (the
armpit) it is 35.5–37.0 °C (95.9–98.6 °F).
Harrison's principles of internal medicine defines a
fever as a morning oral temperature of >37.2 °C
(>98.9 °F) or an afternoon oral temperature of >37.7 °C
(>99.9 °F) while the normal daily temperature variation is
typically 0.5 °C (0.9 °F).
 FEVER CONT’D
Normal body temperatures vary depending on many factors,
including age, sex, time of day, ambient temperature, activity
level, and more.
A raised temperature is not always a fever. For example, the
temperature of a healthy person rises when he or she
exercises, but this is not considered a fever, as the set-point is
normal.
On the other hand, a "normal" temperature may be a fever, if
it is unusually high for that person. For example, medically frail
elderly people have a decreased ability to generate body heat,
so a "normal" temperature of 37.3 °C (99.1 °F) may represent a
clinically significant fever.
 TYPES OF FEVER
Continuous fever: Temperature remains above normal throughout the day and
does not fluctuate more than 1 °C in 24 hours, e.g. lobar pneumonia, typhoid,
meningitis, urinary tract infection, or typhus.
Intermittent fever: The temperature elevation is present only for a certain
period, later cycling back to normal, e.g. malaria, kala-azar, pyaemia, or
septicemia. Following are its types:
• Quotidian fever, with a periodicity of 24 hours, typical of Plasmodium
falciparum or Plasmodium knowlesi malaria
• Tertian fever (48-hour periodicity), typical of Plasmodium vivax or Plasmodium
ovale malaria
• Quartan fever (72-hour periodicity), typical of Plasmodium malariae malaria.
Remittent fever: Temperature remains above normal throughout the day and
fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis, brucellosis.
 Pathophysiology of fever
Temperature is ultimately regulated in the hypothalamus. A trigger of
the fever, called a pyrogen, causes a release of prostaglandin E2 (PGE2).
PGE2 then in turn acts on the hypothalamus, which generates a systemic
response back to the rest of the body, causing heat-creating effects to
match a new temperature level.
In many respects, the hypothalamus works like a thermostat.
When the set point is raised, the body increases its temperature through
both active generation of heat and retention of heat. Peripheral
vasoconstriction both reduces heat loss through the skin and causes the
person to feel cold.
Norepinephrine increases thermogenesis in brown adipose tissue, and
acetylcholine stimulates muscle to raise metabolic rate.
If these measures are insufficient to make the blood temperature in the
brain match the new set point in the hypothalamus, then shivering begins
in order to use muscle movements to produce more heat.
 Pathophysiology of fever cont’d
When the hypothalamic set point moves back to baseline either
spontaneously or with medication, the reverse of these processes
(vasodilation, end of shivering and nonshivering heat production)
and sweating are used to cool the body to the new, lower setting.
This contrasts with hyperthermia, in which the normal setting
remains, and the body overheats through undesirable retention of
excess heat or over-production of heat.
Hyperthermia is usually the result of an excessively hot
environment (heat stroke) or an adverse reaction to drugs.
Fever can be differentiated from hyperthermia by the
circumstances surrounding it and its response to anti-pyretic
medications.
 FEVER CONT’D
A fever can be caused by many medical conditions ranging
from not serious to potentially serious.
This includes viral, bacterial and parasitic infections such as
the common cold, urinary tract infections, meningitis, malaria
and appendicitis among others.
Non-infectious causes include vasculitis, deep vein
thrombosis, side effects of medication, and cancer among
others.
It differs from hyperthermia, in that hyperthermia is an
increase in body temperature over the temperature set-point,
due to either too much heat production or not enough heat
loss.
 FEVER CONT’D
Treatment of associated pain and inflammation, however, may
be useful and help a person rest.
Medications such as ibuprofen or paracetamol
(acetaminophen) may help with this as well as lower
temperature.
Measures such as putting a cool damp cloth on the forehead
and having a slightly warm bath are not useful and may simply
make a person more uncomfortable.
Children younger than three months require medical
attention, as might people with serious medical problems such
as a compromised immune system or people with other
symptoms.
 FEVER CONT’D
Fever is one of the most common medical signs.
It is part of about 30% of healthcare visits by
children and occurs in up to 75% of adults who are
seriously sick.
While fever is a useful defense mechanism,
treating fever does not appear to worsen
outcomes.
Fever is viewed with greater concern by parents
and healthcare professionals than it usually
deserves, a phenomenon known as fever phobia.
 hypothermia
Hypothermia is reduced body temperature that happens when a body
dissipates more heat than it absorbs.
In humans, it is defined as a body core temperature below 35.0 °C
(95.0 °F). Symptoms depend on the temperature. In mild hypothermia
there is shivering and mental confusion.
Hypothermia has two main types of causes. It classically occurs from
exposure to extreme cold. It may also occur from any condition that
decreases heat production or increases heat loss.
Commonly this includes alcohol intoxication but may also include low
blood sugar, anorexia, and advanced age, among others.
Body temperature is usually maintained near a constant level of 36.5–
37.5 °C (97.7–99.5 °F) through thermoregulation.
Efforts to increase body temperature involve shivering, increased
voluntary activity, and putting on warmer clothing.
Hypothermia may be diagnosed based on either a person's symptoms in
the presence of risk factors or by measuring a person's core temperature.
 Hypothermia cont’d
The treatment of mild hypothermia involves warm drinks, warm
clothing and physical activity.
In those with moderate hypothermia heating blankets and warmed
intravenous fluids are recommended.
People with moderate or severe hypothermia should be moved
gently. In severe hypothermia extracorporeal membrane oxygenation
(ECMO) or cardiopulmonary bypass may be useful.
In those without a pulse cardiopulmonary resuscitation (CPR) is
indicated along with the above measures.
Rewarming is typically continued until a person's temperature is
greater than 32 °C (90 °F).
If there is no improvement at this point or the blood potassium level
is greater than 12 mmol/liter at any time resuscitation may be
discontinued.
 hyperthermia
• Hyperthermia is elevated body temperature due to failed
thermoregulation that occurs when a body produces or absorbs
more heat than it dissipates.
• Extreme temperature elevation then becomes a medical emergency
requiring immediate treatment to prevent disability or death.
• The most common causes include heat stroke and adverse reactions
to drugs. The former is an acute temperature elevation caused by
exposure to excessive heat, or combination of heat and humidity,
that overwhelms the heat-regulating mechanisms. The latter is a
relatively rare side effect of many drugs, particularly those that affect
the central nervous system.
• Malignant hyperthermia is a rare complication of some types of
general anesthesia.
 Hyperthermia cont’d
• In humans, hyperthermia is defined as a temperature greater than 37.5–38.3 °C
(99.5–100.9 °F), depending on the reference used, that occurs without a change
in the body's temperature set point.
• The normal human body temperature can be as high as 37.7 °C (99.9 °F) in the
late afternoon.
• Hyperthermia requires an elevation from the temperature that would otherwise
be expected. Such elevations range from mild to extreme; body temperatures
above 40 °C (104 °F) can be life-threatening.
• An early stage of hyperthermia can be "heat exhaustion" (or "heat prostration" or
"heat stress"), whose symptoms include heavy sweating, rapid breathing and a
fast, weak pulse.
• If the condition progresses to heat stroke, then hot, dry, skin is typical as blood
vessels dilate in an attempt to increase heat loss.
• An inability to cool the body through perspiration may cause the skin to feel dry.
 Hyperthermia cont’d
• Other signs and symptoms vary. Accompanying dehydration
can produce nausea, vomiting, headaches, and low blood
pressure and the latter can lead to fainting or dizziness,
especially if the standing position is assumed quickly.
• Heart rate and respiration rate will increase (tachycardia and
tachypnea) as blood pressure drops and the heart attempts to
maintain adequate circulation.
• The decrease in blood pressure can then cause blood vessels to
contract reflexively, resulting in a pale or bluish skin color in
advanced cases.
• Young children, in particular, may have seizures. Eventually,
organ failure, unconsciousness and death will result
 Cerebellar disorders
• As the cerebellum is associated with motor control, lesions produce
a range of movement disorders (ataxias).
• These can be differentiated by their time course. Lesions of the
midline vermis of the cerebellum cause truncal ataxia, while lesions
of the cerebellar hemispheres cause limb ataxia of the ipsilateral
side.
• Ataxia can be particularly difficult to diagnose in children.
Gait ataxia
• Patients will tend to stand with feet well apart and are often
frightened to stand.
• Patients tend to reel to the side of a unilateral lesion, or from side to
side if central or bilateral (even if supported). Walking along a line of
the floor demonstrates minor degrees of gait ataxia.
 Cerebellar disorders
Truncal ataxia
• Patients can't sit or stand unsupported and tend to fall backwards. It
is caused by a midline cerebellar lesion, or may be a feature of post-
chickenpox cerebellar syndrome. Truncal tremor may be evident -
constant jerking of the trunk and head
Limb ataxia
• Lesions of the cerebellar hemisphere cause ipsilateral signs. The
outstretched arm tends to be held hyperpronated at rest and at a
slightly higher level than the unaffected side (Riddoch's sign), and
rebounds upwards if gently pressed downwards and then suddenly
released by the examiner.
• Finger-nose and heel-knee-shin tests will demonstrate even mild
limb ataxia, with terminal intention tremor and dysmetria (past
pointing).
 Cerebellar disorders
Acute-onset ataxia
• Either due to cerebellar haemorrhage or infarction.
Haemorrhage presents with occipital headache, vertigo,
vomiting and altered consciousness.
Episodic ataxias: These are episodes of ataxia lasting minutes
to hours. May appear bizarre and may be misdiagnosed as
being of hysterical origin. There are various causes:
• Drugs.
• Transient vertebrobasilar ischaemic attacks.
• Foramen magnum compression.
• Inherited periodic ataxia, dysarthria, nystagmus and vertigo.
 Cerebellar disorders
Chronic progressive ataxias
• Commonly caused by chronic alcohol abuse associated with malnutrition.
• May improve with thiamine.
• May also occur with other deficiencies, including zinc and vitamin E.
• Other causes include:
• Ingestion of drugs - especially anticonvulsants, particularly phenytoin
(may reverse once the drug is stopped).
• Solvent abuse.
• Heavy metals.
• Structural lesions.
• Paraneoplastic cerebellar degeneration associated with carcinomas of
the lung or ovaries.
 Cerebellar disorders
Cerebellar dysarthria
• Cerebellar disease can produce a spluttering staccato speech.
Scanning dysarthria - jerky and explosive speech with
separated syllables may be demonstrated by asking the patient
to repeat "baby hippopotamus".
Writing
• This may be larger than normal (contrast with micrographia of
Parkinson's disease).
Tremor
• Cerebellar lesions can produce unilateral or bilateral intention
tremor, or a truncal tremor.
 Disorders of basal ganglia
• Basal ganglia disease is a group of physical dysfunctions that occur when the
group of nuclei in the brain known as the basal ganglia fail to properly suppress
unwanted movements or to properly prime upper motor neuroncircuits to
initiate motor function.
• Research indicates that increased output of the basal ganglia inhibits
thalamocortical projection neurons.
• Proper activation or deactivation of these neurons is an integral component for
proper movement.
• If something causes too much basal ganglia output, then the thalamocortical
projection neurons become too inhibited and one cannot initiate voluntary
movement.
• These disorders are known as hypokinetic disorders. However, a disorder leading
to abnormally low output of the basal ganglia leads to relatively no inhibition of
the thalamocortical projection neurons.
• This situation leads to an inability to suppress unwanted movements.
 Disorders of basal ganglia cont’d
• These disorders are known as hyperkinetic disorders.
• Currently, reasons for abnormal increases or decreases of basal
ganglia output are poorly understood.
• One possible factor could be the natural accumulation of iron
in the basal ganglia, causing neurodegeneration due to its
involvement in toxic free-radical reactions.
• Though motor disorders are the most common associated with
the basal ganglia, recent research shows that basal ganglia
disorders can lead to other dysfunctions such as obsessive
compulsive disorder (OCD) and Tourette syndrome.
 Disorders of basal ganglia cont’d
Hypokinetic disorders are movement disorders that are described as having
reduced motor function.
• This is generally attributed to higher than normal basal ganglia output causing
inhibition of thalamocortical motor neurons.
Parkinsonism
• The muscle rigidity, tremor at rest, and slowness in initiation and execution of
movement that are the cardinal motor symptoms of Parkinson's disease are
attributed to a reduction in dopaminergic activity in the basal ganglia motor
areas, particularly the putamen, due to gradually reduced innervation from SNc.
Other motor deficits and common non-motor features of Parkinson's such as
autonomic dysfunction, cognitive impairment, and gait/balance difficulties, are
thought to result from widespread progressive pathological changes commencing
in the lower brain stem and ascending to the midbrain, amygdala, thalamus and
ultimately the cerebral cortex.
 Disorders of basal ganglia cont’d
Hyperkinetic disorders are movement disorders characterized by
increased uncontrollable motor function.
• They are caused by reduced basal ganglia output, which causes increased
thalamocortical function which lead to the inability to stop unwanted
movement.
Huntington's disease is a hereditary disease that causes defects in
behavior, cognition, and uncontrolled rapid, jerky movements.
Huntington’s disease stems from a defect that consists of an expanded
CAG repeat in a gene located on chromosome 4p.
• Evidence shows that the basal ganglias in patients with Huntington’s
Disease show a decrease in activity of the mitochondrial pathway,
complex II-III. Such deficiencies are often associated with basal ganglia
degeneration.
• This degeneration of striatal neurons projecting to GPe leads to
disinhibition of the indirect pathway, increased inhibition of STN, and
therefore, reduced output of the basal ganglia. The neuronal
degeneration eventually causes death within 10 to 20 years.
 Disorders of basal ganglia
Dystonia is hyperkinetic movement disorder that is characterized by
involuntary movement and the slowing of intentional movement.
• Though there are known causes of dystonia such as metabolic,
vascular, and structural abnormalities, there are still patients with
dystonia with no apparent cause.
• Dystonia can occur as a hyperkinetic disorder or as a side effect of
hypokinetic disorders such as Parkinson’s disease.
• Until recently it was thought that dystonia was likely caused by
extreme lack of function of the direct pathway between the Putamen
and the GPi.
• Again, it was thought that this dysfunction lead to a decrease in basal
ganglia output to the thalamus and a resultant increased
disinhibition of the thalamic projections to the premotor and motor
cortex.
• However recent models in mice show that the dysfunction in the
cerebellum may play an equal part in dystonia.
 Disorders of basal ganglia cont’d
Hemiballismus is a hyperkinetic movement disorder
that causes uncontrolled movement on one side of the
body.
• It is generally caused by damage to the subthalamic
nucleus (STN).
• Since the internal segment of the globus pallidus (GPi) is
the link in the circuit between the STN and thalamic
projection, destruction of localized brain cells in the GPi
via a pallidotony has proven to serve as a useful
treatment for Hemiballismus.
Other basal ganglia diseases
•The following diseases that generally involve
the basal ganglia do not clearly fit into being
either hypo- or hyperkinetic:
•Lesch-Nyhan syndrome
•Wilson's disease
•Blepharospasm in some cases
•Athymhormic syndrome (PAP syndrome)
 Brain stem lesion
Brain stem lesions: Diseases of the brain stem
can result to abnormalities in the function of
cranial nerves which may lead to visual
disturbances, pupil abnormalities, changes in
sensation, muscle weakness, hearing problems,
vertigo, swallowing and speech difficulty, voice
change, and co-ordination problems.
 Alzhmeire’s disease
• Alzheimer's disease (AD), also referred to simply as Alzheimer's, is a
chronic neurodegenerative disease that usually starts slowly and
worsens over time.
• It is the cause of 60% to 70% of cases of dementia. The most
common early symptom is difficulty in remembering recent events
(short-term memory loss).
• As the disease advances, symptoms can include problems with
language, disorientation (including easily getting lost), mood swings,
loss of motivation, not managing self care, and behavioural issues.
• As a person's condition declines, they often withdraw from family
and society. Gradually, bodily functions are lost, ultimately leading to
death.
• Although the speed of progression can vary, the average life
expectancy following diagnosis is three to nine years.
 Alzhmeire’s disease cont’d
• The cause of Alzheimer's disease is poorly understood. About 70% of
the risk is believed to be genetic with many genes usually involved.
Other risk factors include a history of head injuries, depression, or
hypertension.
• The disease process is associated with plaques and tangles in the
brain. A probable diagnosis is based on the history of the illness and
cognitive testing with medical imaging and blood tests to rule out
other possible causes.
• Initial symptoms are often mistaken for normal ageing. Examination
of brain tissue is needed for a definite diagnosis.
• Mental and physical exercise, and avoiding obesity may decrease the
risk of AD; however, evidence to support these recommendations is
not strong. There are no medications or supplements that decrease
risk.
 Alzhmeire’s disease
• No treatments stop or reverse its progression, though some may temporarily
improve symptoms.
• Affected people increasingly rely on others for assistance, often placing a burden
on the caregiver; the pressures can include social, psychological, physical, and
economic elements.
• Exercise programmes may be beneficial with respect to activities of daily living
and can potentially improve outcomes.
• Treatment of behavioural problems or psychosis due to dementia with
antipsychotics is common, but not usually recommended, as there is little benefit
with an increased risk of early death.
• In 2015, there were approximately 29.8 million people worldwide with AD. It
most often begins in people over 65 years of age, although 4% to 5% of cases are
early-onset Alzheimer's which begin before this. It affects about 6% of people 65
years and older.
• In 2015, dementia resulted in about 1.9 million deaths. It was first described by,
and later named after, German psychiatrist and pathologist Alois Alzheimer in
1906. In developed countries, AD is one of the most financially costly diseases.
 Dyslexia
• Dyslexia, also known as reading disorder, is characterized by
trouble with reading despite normal intelligence.
• Different people are affected to varying degrees.
• Problems may include difficulties in spelling words, reading
quickly, writing words, "sounding out" words in the head,
pronouncing words when reading aloud and understanding
what one reads.
• Often these difficulties are first noticed at school. When
someone who previously could read loses their ability, it is
known as alexia.
• The difficulties are involuntary and people with this disorder
have a normal desire to learn.
 Dyslexia cont’d
• Dyslexia is believed to be caused by both genetic and environmental
factors.
• Some cases run in families. It often occurs in people with attention
deficit hyperactivity disorder (ADHD) and is associated with similar
difficulties with numbers.
• It may begin in adulthood as the result of a traumatic brain injury,
stroke, or dementia.
• The underlying mechanisms of dyslexia are problems within the
brains language processing.
• Dyslexia is diagnosed through a series of tests of memory, spelling,
vision, and reading skills.
• Dyslexia is separate from reading difficulties caused by hearing or
vision problems or by insufficient teaching.
 Dyslexia cont’d
• Treatment involves adjusting teaching methods to meet the
person's needs. While not curing the underlying problem, it
may decrease the degree of symptoms.
• Treatments targeting vision are not effective.
• Dyslexia is the most common learning disability and occurs in
all areas of the world. It affects 3–7% of the population,
however, up to 20% may have some degree of symptoms.
While dyslexia is more often diagnosed in men, it has been
suggested that it affects men and women equally.
• Some believe that dyslexia should be best considered as a
different way of learning, with both benefits and downsides.
 Disorders of reticular activating system (RAS)
What are the functions of Reticular activating system?
• The most important function of Reticular activating system is to
regulate the shift between sleep and wakefulness.
• The transition made by our body from deep slumber to being
completely awake as well as functional and vice versa is under the
control of this system.
• It also plays a vital role during our sleep and when we see dreams. It
is also responsible for supplying integrated response to the outside
stimuli.
• The skill to sluice out information brought out by the external
sources and to pin point a particular fact with detailed thought is the
controlled effect of the reticular activating system.
• Coordination while walking, eating or sexual functions are carried
out by RAS.
 Disorders of RAS cont’d
•Reticular activating system damage can make the
patient go to coma. Since it is placed at the back of
brain, it is more vulnerable to injury or damage.
•The disorders in RAS are attention deficit disorders,
narcolepsy, sleep disorders, Alzheimer’s disease.
•The psychotropic drugs or the anesthetics affect
this system directly which makes the transition
from unconsciousness to semi consciousness
possible.
 Neuroplasticity
• Neuroplasticity, also known as brain plasticity or neural plasticity, is an umbrella term that
describes lasting change to the brain throughout an individual's life course.
• The term gained prominence in the latter half of the 20th century, when new research
showed that many aspects of the brain can be altered (or are "plastic") even into
adulthood.
• This notion is in contrast with the previous scientific consensus that the brain develops
during a critical period in early childhood and then remains relatively unchanged (or
"static").
• Neuroplasticity can be observed at multiple scales, from microscopic changes in individual
neurons to larger-scale changes such as cortical remapping in response to injury.
• However, cortical remapping is more extensive early in development.
• Behavior, environmental stimuli, thought, and emotions may also cause neuroplastic
change through activity-dependent plasticity, which has significant implications for healthy
development, learning, memory, and recovery from brain damage.
• At the single cell level, synaptic plasticity refers to changes in the connections between
neurons, whereas non-synaptic plasticity refers to changes in their intrinsic excitability.
 Myasthenia gravis
 Myasthenia gravis (MG) is a long-term neuromuscular disease that leads
to varying degrees of skeletal muscle weakness.
• The most commonly affected muscles are those of the eyes, face, and
swallowing. It can result in double vision, drooping eyelids, trouble
talking, and trouble walking. Onset can be sudden.
• Those affected often have a large thymus gland or develop a thymoma.
• Myasthenia gravis is an autoimmune disease which results from
antibodies that block or destroy nicotinic acetylcholine receptors at the
junction between the nerve and muscle.
• This prevents nerve impulses from triggering muscle contractions.
• Rarely, an inherited genetic defect in the neuromuscular junction results
in a similar condition known as congenital myasthenia.
• Babies of mothers with myasthenia may have symptoms during their first
few months of life, known as neonatal myasthenia.
• Diagnosis can be supported by blood tests for specific antibodies, the
edrophonium test, or nerve conduction studies.
 Myasthenia gravis cont’d
• Myasthenia gravis is generally treated with medications known as
acetylcholinesterase inhibitors such as neostigmine and pyridostigmine.
• Immunosuppressants, such as prednisone or azathioprine, may also be
used.
• The surgical removal of the thymus gland may improve symptoms in
certain cases. Plasmapheresis and high dose intravenous immunoglobulin
may be used during sudden flares of the condition.
• If the breathing muscles become significantly weak, mechanical
ventilation may be required.
• Myasthenia gravis affects 50 to 200 per million people. It is newly
diagnosed in three to 30 per million people each year.
• Diagnosis is becoming more common due to increased awareness.
• It most commonly occurs in women under the age of 40 and in men over
the age of 60. It is uncommon in children.
• With treatment, most of those affected lead relatively normal lives and
have a normal life expectancy.