NEURO OTHER MYASTHENIC SYNDROMES: DR LOKIN, SEPT.

5 2012


OTHER MYASTHENIC SYNDROMES
MYASTHENIC SYNDROME (LAMBERT-EATON;
LEMS)
Epidemiology
Prevalence: 1 in 100,000
Males slightly more common than Female
Age: 17 to 75 years; Onset younger without
associated neoplasm
Clinical features
Onset
Weakness (82%), especially legs
Age: Range =7 to 80 years
Usually precedes cancer: >80%
Weakness
Proximal >Distal
Legs (98%) & Arms (82%)
Neck (30%)
Respiratory (15%): Rarely severe
Bulbar: Dysphagia (22% to 56%); Dysarthria (Up
to 80%)
Improves with: Brief sustained exercise
May worsen with: Sustained exercise; Heat or
Fever
Fatigability (33%)
Extraocular muscles
Not involved at presentation
Rarely involved on examination
Occasional ptosis (30% to 50%)
Symptomatic diplopia in ~40%: Transient
Muscle pain: Occasional
Sensory neuropathy: Distal; Symmetric
Autonomic neuropathy
Association stronger with cancer than with
LEMS
Dry mouth >eyes
Impotence: Males
Other (10% to 50%): Bladder; Obstipation;
Hypohidrosis
Associated syndromes
CNS
Ataxia (5% to 10%)
Encephalopathy
More common in paraneoplastic LEMS
Weight loss (24%)
"Viral" prodrome (34%)
Differences from
LEMS never begins with ocular weakness
LEMS usually has weakness in Legs >Arms

Usually related with a malignancy SCCA
Pathophysiology: Presynaptic disorder
Reduced numbers of P/Q Ca++channels on
presynaptic terminals
Ultrastructure: Active zone particles on
presynaptic terminals reduced
Physiology
Reduced K+ stimulated Ca++ flux into
presynaptic terminals
Reduced Ca++ dependent quantal ACh
release

Electrophysiology
Repetitive nerve stimulation
Increment
After rapid (50 Hz) RNS, or
Sustained muscle contraction
Prolonged by cooling
Muscles with most increment after 10
sec maximal voluntary contracture
Most specific for LEMS when >100%
in several muscles or >400% in one
muscle
o Abductor digiti minimi; Abductor
policis brevis; Anconeus
Decrement on slow (5 Hz) RNS: Especially
in small hand muscles

BOTULISM
Forgotten disease in modern day because of
better food handling, but still exists in poorer
nations
Botox more popular for cosmetic purposes
EMG/NCV/RNS findings similar to LEMS
cause by toxin from the anaerobic bacteria,
Clostridium botulinum, which blocks release of
Ach from the nerve terminal
Of 8 types, A & B causes most cases in US, type
E comes from seafood
SYMPTOMS
Nausea & vomiting are 1st symptoms
Neuromuscular features appear in 12-36 hrs
initial symptoms: BOV, dysphagia, dysarthria
Dilated pupils
Descending weakness progresses for 4-5 days
than plateaus
Respiratory paralysis may occur rapidly
Most have autonomic dysfunction
TREATMENT
Trivalent (A,B,E)antitoxin
Antibiotics not effective
Supportive therapy inc. respiratory assistance
ChE inhibitors not beneficial
guanidine or DAP may improve strength
Recovery takes many months but is usually
complete!!

(Did my best to transcribe this part! )
MORE COMMON MUSCLE DISEASES

HISTORY
weakness proximal, acute, chronic, episodic
swallowing, speech, extraocular movement
respiratory and cardiac symptoms
no sensory loss
muscle pains/cramps
twitches
abnormal posture
FAMILY HISTORY
past medical history of muscular disease
drugs/substance abuse (common drug used today
that can cause muscular problems =statins)
PHYSICAL EXAM
Musculoskeletal
proximal weakness
normal/late loss of muscle use
pseudohypertrophy
muscle tenderness
no sensory loss
CNS
distal weakness
early hyporeflexia/areflexia
atrophy
dysesthesias
sensory loss
NEURO OTHER MYASTHENIC SYNDROMES: DR LOKIN, SEPT. 5 2012

DIAGNOSTICS
muscle enzymes =CPK, aldolase
EMG NCV
Radiologic X-rays, MRIs, NMS
Muscle biopsy
Disease-specfic exams
Gene analysis

CLASSIFICATION OF PRIMARY MYOPATHIES
Inherited Myopathies
Metabolic myopathies
Dystropinopathies
Acquired Myopathies
Inflammatory myopathies
Toxic myopathies
Endocrine myopathies

INHERITED MYOPATHIES:
MUSCULAR DYSTROPHIES

CLASSIFICATIONS
X-Linked Recessive
- Duchennes muscular dystrophy
- Beckers muscular dystrophy
- Emery-Dreifuss muscular dystrophy
Autosomal Recessive
- Limb girdle
- Scapulohumoral
-
Autosomal Dominant
- Facioscapulohumoral.

DUCHENNES MUSCULAR DYSTROPHY
- Onset <5 yrs of age
- Progressive weakness of girdle muscle.
- Genotype: dystrophin absence
96% of patients exhibit a frameshift
mutation
30% of patients have a new mutation
- Clinical finding: weakness
Distribution: proximal >distal
Diagnostic Criteria
1. Weakness with onset in legs
2. Hyperlordosis with wide and based gait
3. Hypertrophy of weak muscle
4. Progressive course over time
- Absence of bowel dysfunction
Course
- Decreased motor function by 2-3 years
- Steady decline in strength after 6-10 years
- Gowers sign
- Failure to walk in 9-13 years
Muscular hypertrophy
- *Found especially in the calf muscle*
- May be generalized
- Increases with age
- Most commonly due to muscular fibrosis
Musculoskeletal
- Contractures esp. ankles! Also found in hips
and knees
- Scoliosis
onset after loss of ambulation
may be decreased if walking/standing for
prolonged periods of time
tx: spinal rod
Other clinical features
- cardiomyopathy >15 y/o
- mental retardation
- night blindness
- death
15-25 y/o
due to respiratory or cardiac failure
life prolonged with respiratory and cardiac
support
Labs
serum
CK very high
Troponin I elevated
Liver enzymes high AST/ALT
Muscle biopsy General features
Small rounded fibers
Myopathic grouping
Degeneration/regeneration
Absent dystrophin, decreased sarcoglycans and
aquaporin 4
Myopathic regrouping of muscular fibers
Diagnostic Testing
Muscles: stain for dystrophin protein absent
(paulit-ulit na ito!)
Genetic : deletion, duplication, small mutation,
point mutation (nice to know)
Drug Treatment
Prolongs ability to walk by 2-3 years (but does
not alter disease
Prednisone

BECKERS MUSCULAR DYSTROPHY
Genotype: dystrophin mutations
Deletion
70% of patients inframe mutation
16% of patients frameshift mutation
New mutations rare
Point mutations
70% identified.
Worse course: mutation in myogenic factor 6
Clinical features
onset >7 yrs
weakness
proximal >distal, symmetric, legs and arms
prominent in quadriceps or hamstrings
calf pain on exercise
failure to walk 16-80 yrs
Systemic
joint contractions: ankles
cardiomyopathy
mental retardation
deletion of Dp140 transcription unit
serum CK.
Muscle biopsy
myopathic
<12 y/o
Degeneration/regeneration pattern
REDUCED dystrophin staining (compare to
Duchennes where there is ABSENT dystrophin)

Myopathic grouping

Older patients
Findings typical of chronic dystrophies
Largest muscle fibers hypertrophied
Regeneration/degeneration pattern
Myopathic grouping
Regeneration
Medial-sized..

METABOLIC MYOPATHIES
Metabolic
1. Thyrotoxic myopathy
2. Hypothyroidism
Percussion provokes prolonged.
3. Period paralysis (read the book daw)
Autosomal dominant
NEURO OTHER MYASTHENIC SYNDROMES: DR LOKIN, SEPT. 5 2012

Males predominantly affected (i.e. dock
workers these patients are often tired,
work all day, and eat lots of rice)
Mechanism: mutation of Na+channel
Triggered by CHO loading, exercise, cold
Sudden attacks
Hypokalemic / hyperkalemic / eukalemic
Channelopathies?
4. Alcoholic myopathy
Insidious proximal weakness, low CPK
Acute rhabdomyolysis may accompany
binge drinking

ACQUIRED MYOPATHY
Inflammatory
Polymyositis
Dermatomyositis
IBM
(Dr. Lokin says please read the additional slides
he will provide regarding these diseases)

INFLAMMATORY MYOPATHIES
Cause inflammation and degeneration of skeletal
muscle tissue

CLASSIFICATIONS
Idiopathic IM
Largest group
Secondary
Associated with other systemic
problems
Infantile / childhood
Miscellaneous forms

IDIOPATHIC IM
Characteristic symptom: MUSCULAR
WEAKNESS
Male-female ratio
PM 1:1
DM 1:2
IBM 3:1
Age for DM is bimodal (5-10 and 45-50 yrs)
Age for PM: 40-60 y/o
Age for IBM >50 y/o
Race: more frequent among African-Americans
Autoimmune pathogenesis
T-clel mediated myocytotoxicity
Complement-mediated..
Etiology
Multifactorial
Genetic predisposition
Environmental factors
Overall clinical features
1 in 100,000
DM found in children and adults
PM found in 2
nd
Commom myopathies: difficulty in getting out of
chair, combing hair, etc.
decade of life
IBM: distal weakness common
Facial muscles spared except in late stages
Wasting
Normal weakness