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Neuromuscular Junction Disorders

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Title: Neuromuscular Junction Disorders


1
Neuromuscular Junction Disorders
  • Abdullah Al-Salti R3
  • AHD 9 march 2011

2
Neuromuscular junction
3

Myasthenia Gravis
  • Myasthenia Gravis
  • a chronic autoimmune neuromuscular disease
    characterized by varying degrees of weakness of
    the skeletal (voluntary) muscles of the body.
  • Age and Gender
  • Myasthenia gravis presents at any age. Female
    incidence peaks in the third decade of life,
    whereas male incidence peaks in the sixth or
    seventh decade.
  • The female-to-male ratio is said classically to
    be 64, but as the population has aged, the
    incidence is now equal in males and female
  • Inheritance
  • 1st degree relatives have 1000x the rest of
    general population
  • inc. jitter on SFEMG demonstrated in 33-45 of
    asymptomatic 1st degree relatives
  • Inc. titres of AChR antibodies in up to 50

4
Pathophysiology
  • Immunoglobulin G (IgG) directed attack on the
    NMJ, aimed specifically at the nicotinic
    acetylcholine (ACH) receptor.
  • Damage to the ACH receptor and postsynaptic
    membrane involves several steps.
  • First, binding of the antibody to the receptor
    can directly block the binding of ACH.
  • Second, there is a complement-directed attack,
    with destruction of the ACH receptor and post
    junctional folds.
  • Third antibody binding can result in an increase
    in the normal removal of ACH receptors from the
    postsynaptic membrane.
  • Resulting in a smaller endplate potential and a
    reduced safety factor of NMJ transmission.

5
Pathophysiology
  • The MuSK
  • maintains the normal functional integrity of the
    NMJ
  • anti-MuSK antibodies may alter the normal
    maintenance of a high density of AChRs at the NMJ
  • leading to reduced numbers of functional AChRs.
  • Thymus gland.
  • greater than 50 of anti AChR-positive patients
    having thymic hyperplasia and 10 to 15 having a
    thymic tumor.

6
  1. HLA-DRW3, -B8, and -A1 predispose
  2. a-subunit is the major T cell antigen

7
Etiology
  • Acquired autoimmune
  • Drug-induced D-penicillamine
  • Transient neonatal (passive transfer of maternal
    anti-AChR antibodies)
  • Congenital myasthenic syndrome

8
Clinical presentation
  • most commonly presents with weakness of
    extraocular muscles ptosis and/or diplopia, /-
    photophobia
  • can mimic any pattern of ophthalmoplegia
    including pupil sparing IIIrd nerve palsy,
    internuclear ophthalmoplegia (INO) or sixth nerve
    palsy
  • Bulbar involvement common eventually dysphagia,
    dysarthria, dysphonia (hypernasal or hoarse)
  • reduced facial expression, jaw fatigue
  • generally progresses over time so that within 2
    years of onset of ocular MG, 90 have bulbar and
    proximal symmetric limb weakness

9
Clinical presentation
  • Early Symptoms
  • frequent purchase of new eyeglasses to correct
    blurred vision
  • sleepy or sad facial appearance
  • avoidance of difficult to chew foods
  • cessation of activities requiring specific
    muscles (e.g. singing)
  • Presenting Symptoms
  • ptosis or diplopia (2/3 of patients)
  • present in almost all within 2 years of onset
  • difficulty chewing, swallowing, talking (1/6)
  • limb weakness (1/10)
  • Rarely limited to single muscle group
  • Diurnal Variation
  • Exacerbating Factors

10
Clinical presentation
  • Natural History
  • Restricted to ocular muscles in 10 of patients.
  • 90 have progressive weakness over two years
    involving oropharyngeal and limb muscles.
  • 2/3 of patients reach remission within 1 year
  • Spontaneous remission can occur, usually early
  • Stages
  • Active stage
  • brief period of fluctuation
  • more severe
  • Inactive stage
  • fluctuations attributable to fatigue,
    intercurrent illness
  • Burnt out stage (15-20 years)
  • fixed weakness
  • atrophic muscles

11
Physical Findings
  • Ocular Muscles
  • Ptosis
  • assymetrical
  • covering ptotic lid may relieve contraction of
    opposite frontalis
  • passively lifting ptotic lid may cause opposite
    lid to fall
  • varies during sustained activity
  • may shift from eye to eye - pathognomonic
  • edrophonium response
  • EOMs
  • ³N muscle without pupil involvement
  • variable, fluctuating, and fatigable
  • most severe in medial rectus
  • pseudo-INO
  • edrophonium may improve only one of several weak
    ocular muscles

12
Physical Findings
  • Oropharyngeal Muscles
  • altered facial appearance depressed , snarl/sad
  • examiner can manually open jaw against resistance
  • impaired strength of eye closure
  • nasal regurgitation
  • difficulty swallowing
  • hoarseness (larynx)
  • nasal voice, especially after prolonged talking
  • Limb Muscles
  • neck flexors gt extensors
  • deltoids, triceps, wrist extensors, finger
    extensors especially affected
  • ankle dorsiflexors preferentially affected
  • fatigability

13
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15
Diagnostic Procedures

16
Tensilon test
  • Measures
  • ptosis, limitation of eye movement, or nasal
    speech preferred
  • limb muscles (requires maximum effort)
  • Administration
  • 2mg then wait 60s then 8mg then wait 60s
  • total dose 0.15mg/kg in children
  • sc administration in newborns and infants
    (delayed 2-5 minutes)
  • Test Characteristics
  • 90 sensitivity not 100 specificity
  • motor neuron disease
  • oculomotor nerve palsies
  • Alternative Agents
  • im neostigmine (longer duration of action)
  • therapeutic trial of pyridostigmine

17
Tensilon test
18
Antibodies Against Acetylcholine Receptors
  • Value
  • confirm diagnosis but cant predict severity
    neither predict thymoma
  • Test Characteristics
  • 80 sensitivity for generalized myasthenia (range
    74-99)
  • 55 sensitivity for ocular myasthenia
  • may rise with disease progression
  • generally specific
  • rare DDx
  • SLE
  • Inflammatory neuropathy (CIDP)
  • ALS
  • RA
  • Thymoma without MG
  • Normal relatives of patients with MG

19
Ocular cooling
  • Specificity??
  • Positive 80, no positive response in patients
    with ptosis not due to myasthenia
  • Alternative to tensilon test
  • Improvement in lid ptosis after the eye is cooled
    with ice pack 2 minutes

20
Repetitive nerve stimulation
  • (CMAP) should be normal in patients with MG.
  • With a small CMAP, LEMS should be considered.
  • Reproducible 10 decremental in amplitude when
    the first stimulus is compared to fourth or fifth
  • skin temperature (i.e. 32ºC 34ºC) before
    beginning RNS.
  • hold anticholinesterases before test
  • more common in proximal muscles (facial, biceps,
    deltoid, trapezius)
  • may get some repair with exercise, but not an
    increment (unlike LEMS)
  • RNS in hand/shoulder has sensitivity of 61
  • 76 in generalized myasthenia
  • 48 in ocular myasthenia

21
Repetitive nerve stimulation
22
SFEMG
  • (MUAP) abnormalities suggestive of a NMJ
    disorder,unstable MUAP, small, short-duration.
  • At least one symptomatic muscle
  • Increased jitter and blocking
  • Jitter is greatest in weak muscles
  • Measure 2 time locked motor units
  • SENSITIVE 99 sensitive for generalized and 97
    sensitive for ocular
  • NONSPECIFIC
  • any other motor unit disease
  • must perform EMG and NCS to exclude neuronopathy,
    neuropathy, myopathy
  • limb jitter DOES NOT predict development of
    generalized myasthenia
  • should examine 20 pairs in each muscle

23
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24
Sensitivity
test ocular generalized
tensilon 60-95 72-95
Ach rec. Ab1 50-75 70-95
Anti-Musk 50 of AchR -
RNS 50 75
SFEMG 90-95 98-100
Ocular cooling2 89 89
25
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26
Comparison of Diagnostic Techniques
  • Tensilon test diagnostic if positive in patients
    with ptosis or ophthalmoparesis
  • AChR Ab specific
  • RNS confirms DNMJ transmission but nonspecific
    often normal in mild or ocular disease
  • SFEMG sensitive but not specific
  • Other Diagnostic Procedures
  • CT chest
  • TFTs
  • TB test prior to immunosupression

27
Treatment
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29
Treatment
  • Cholinesterase Inhibitors
  • Roles
  • diagnostic
  • early, symptomatic treatment
  • adjunct to immunomodulatory and immunosuppressive
    therapy.
  • RARELY can be used as chronic treatment
  • usually effect diminishes with time
  • Dosing
  • Pyridostigmine
  • longer duration of action
  • initially 30-60mg q4-8 hours
  • 1.0mg/kg in infants and children
  • available in serum (60mg/5ml)
  • available as nebulizer
  • RARELY produces normal strength and RARELY
    completely corrects diplopia

30
Treatment
  • Cholinesterase Inhibitors
  • Neostigmine
  • initially 7.5-15.0mg q4-8h
  • 0.3mg/kg in infants and children
  • available as IV and nebulizer
  • Side Effects
  • Smooth Muscle (muscarinic)
  • NxVx
  • cramps
  • diarrhea
  • Rx with loperamide, propantheline,
    glycopyrrolate, diphenozylate
  • Autonomic (muscarinic)
  • bronchial/oral secretions

31
Treatment
  • Cholinesterase Inhibitors
  • Skeletal Muscle (nicotinic)
  • weakness
  • Bromism (from Mestinon)
  • acute psychosis
  • rash
  • measure bromine level
  • Drug Interactions
  • succinylcholine metabolized by
    acetylcholinesterase impaired metabolism can
    lead to potential arrythmias

32
Corticosteroids
  • Efficacy
  • marked improvement or complete relief in 75
  • some improvement in 25
  • most improvement in 6-8 weeks
  • may become total remission even later
  • best response if treated early
  • severity does not predict response
  • respond better with shorter disease duration and
    younger lt50
  • Initiation - standard
  • begin with 1.5-2.0mg/kg/day
  • given until sustained improvement (2 weeks) then
    changed to 100-120mg alternate days
  • Initiation - alternative
  • begin at 20mg qd
  • increase in 10mg increments q1-2 weeks
  • then maintain constant until improvement is
    maximum
  • used in ocular myasthenia

33
Corticosteroids
  • Taper
  • decrease to lowest dose necessary to maintain
    improvement
  • by 20mg each month until dose is 60mg
  • by 10mg each month until dose is 20mg
  • by 5mg each 3 months until 10 every other day
  • if weakness occurs, increase prednisone or add
    another immunosuppressant
  • do not d/c altogether
  • Initial Worsening
  • 1/3 of patients
  • within 1st 7-10 days and lasts 6 days
  • cover with ChE inhibitors
  • use initial PLEX and do in hospital if
    oropharyngeal weakness or respiratory
    insufficiency

34
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35
Immunosupressants
  • Azathioprine
  • Regimen
  • start 50mg/d
  • 50mg/d q7d
  • target 150-200mg/d
  • Efficacy
  • improvement maintained
  • ?synergistic with steroids
  • may start simultaneous with steroids and taper
    steroids when azathioprine kicks in
  • effect takes 4-8 months
  • maximum improvement within 12 months
  • 70-90 response rate similar to steroids

36
Immunosupressants
  • Azathioprine
  • severe allergic reaction (required
    discontinuation)
  • 2 weeks after initiation
  • 15-30
  • flu-like symptoms and rash
  • GI irritation (use divided doses after meals or
    decrease dose)
  • leucopenia (monitor CBC q1wk x1m, q1m x1y, q3-6m
    after)
  • Transaminitis
  • stop only if gt2x normal and can restart at lower
    dose once normalize
  • no proven increase in malignancy in MG patient
    specifically (unlike in SLE)

37
Immunosupressants
  • Cyclosporine
  • Regimen
  • begin at 5-6mg/kd div q12h
  • trough levels after 1 month (allows tissue
    saturation) - aim for 75-150ng/ml
  • Efficacy
  • improvement in most patients taking CYA
  • improve within 1-2 months
  • maximum improvement at gt6months
  • SFX
  • Renal toxicity .
  • HTN (monitor q1month until steady state)
  • drug interactions

38
Immunosupressants
  • Cyclophosphamide
  • Use
  • severe, refractory MG
  • Regimen
  • 200mg/m2 q1month
  • titrate to changes in strength and side effects
  • 150-200mg/d po to total of 5-10g to relieve Sx
  • SFX
  • alopecia
  • cystitis
  • leucopenia
  • NxVx anorexia

39
Immunosupressants
  • Mycophenolate Mofetil
  • Mechanism
  • Selectively inhibits proliferation of B- and T-
    lymphocyte clones responding to antigenic
    stimulation
  • Suppresses formation of antibodies
  • Evidence
  • Open label pilot study demonstrated role as
    adjunctive therapy in refractory MG
  • Dosing
  • 2g/d div bid
  • Efficacy
  • Improvement as early as 2 weeks and usually seen
    within 2 months
  • Role
  • Refractory MG
  • Steroid sparing agent when imuran intolerable or
    ineffective
  • Side Effects
  • Diarrhea
  • leukopenia

40
Plasma Exchange
  • Roles
  • sudden worsening of myasthenic symptoms for any
    reason
  • rapidly improve strength before surgery
  • concomitantly with high dose steroids
  • chronic intermittent Rx in refractory MG
  • Protocol
  • 2-3L of plasma 3x per week until improvement
    plateaus (usually after 5-6 exchanges)
  • Adverse Effects
  • cardiac arrhythmias
  • Lightheadedness
  • Chills
  • Obscured vision
  • Pedal edema
  • Hemorrhage (removal of coagulation factors)
  • Hypercoagulation (removal of antithrombin III)
  • Coagulation defects corrected within24h

41
IVIG
  • Indications
  • Similar to PLEX
  • Mechanisms
  • blocks Fc receptors on macrophagesm
  • anti-idiotype Ab against AChR antibodies
  • Protocol
  • 2g/kg over 2-5 days
  • SFX
  • Headache , fever and chills, alopecia, aseptic
    meningitis, leucopenia
  • retinal necrosis, renal failure.

42
Treatment
43
  • Other Types Of Myasthenia Gravies

44
Transitory Neonatal Myasthenia
  • clinical features
  • hypotonic
  • onset within hours of birth but can be delayed up
    to 3 days
  • feed poorly in 1st 3 days
  • can get weak cry and lack of facial expression in
    50
  • 15 have limited EOM and ptosis
  • respiratory insufficiency rare
  • worsens for first few days then improves
  • last 2-12 weeks (usually 2 weeks)
  • neonatal antibodies have half life of 2-3 weeks
    and not detected after 5 months
  • recovery is complete

45
Transitory Neonatal Myasthenia
  • diagnosis
  • tensilon test OR RNS
  • high AChR in neonate blood
  • treatment
  • ChE for swallowing or breathing - just before
    feeding
  • neostigmine im before feeding
  • can also give via NG tube at 10 times parenteral
    level
  • PLEX if respiratory weakness (rare).

46
Anti-Musk Myasthenia
  • Epidemiology
  • 25 of all MG patients are seronegative
  • 40 of seronegative MG patients are MuSK positive
    (about 10 overall)
  • MF
  • Same age of onset as usual myasthenia
  • Normal Function of MuSK
  • Tyrosine kinase
  • Regulates and maintains AChR at NMJ
  • Clinical Features Differences from Typical
    Myasthenia
  • More involvement of neck, shoulder, respiratory
  • Less limb
  • More bulbar
  • Increased risk of myasthenic crisis in 1st 2
    years
  • Greater proportion in more severe category
  • Outcome similar, but require more steroids
  • Treatment
  • Treatment generally the same
  • Can respond to thymectomy
  • Less likely to have thymic hyperplasia

47
Genetic Myasthenic SyndromesCongenital
Myasthenia
  • Genetics
  • several genetic defects
  • Epidemiology
  • 21 male predominance
  • Causes
  • Deficiency of muscle acetylcholine receptors at
    the end plate
  • Some have AChR mutations
  • Some have deficiency of rapsyn (receptor-associate
    d protein at the synapse)
  • Abnormalities of acetylcholine resynthesis or
    immoblilization
  • Reduced end plate acetylcholinesterase
  • Impaired AChR function

48
Genetic Myasthenic SyndromesCongenital
Myasthenia
  • Clinical Features
  • ophthalmoparesis and ptosis developing in infancy
  • incomplete at onset
  • progresses to complete paralysis during infancy
    or childhood
  • mild facial paresis
  • limb weakness mild compared to opthalmoplegia
  • respiratory distress unusual
  • symptoms may not fluctuate much

49
Genetic Myasthenic SyndromesCongenital
Myasthenia
  • Diagnosis
  • subcutaneous injection of edrophonium ?
    transitory improvement in ocular motility
  • RNS
  • Decrement found in some limb muscles
  • May be necessary to test proximal or facial
    muscles if limbs normal
  • SFEMG
  • Treatment
  • ChE inhibitors improve limb weakness in many
    forms
  • Ocular muscle weakness less responsive
  • Some children respond to DAP

50
Congenital Myasthenic Syndrome with Episodic
Apnea (Familial Infantile Myasthenia)
  • Clinical Features
  • Similar problems in other siblings
  • generalized hypotonic at birth /- arthrogryposis
  • respiratory insufficiency and feeding difficulty
    at birth
  • repeated episodes of life-threatening apnea and
    feeding difficulty neonatally
  • may require ventilation
  • usually improves within weeks of birth, allowing
    weaning from ventilation
  • episodes may persist throughout infancy and even
    into adulthood
  • sudden bouts of respiratory distress with
    intercurrent illness
  • ocular function usually normal

51
Congenital Myasthenic Syndrome with Episodic
Apnea (Familial Infantile Myasthenia)
  • Diagnosis
  • edrophonium test - 0.15mg/kg
  • decremental RNS
  • Treatment
  • ChE inhibitors improve strength in most children
    - long term to prevent episodes of apnea at time
    of intercurrent illness
  • DAP pyridostigmine works for children from
    several families
  • many require mechanical ventilation

52
Slow-Channel Congenital Myasthenic Syndrome
  • Epidemiology
  • RARE
  • Genetics and Molecular Biology
  • AD
  • Prolonged open time of Ach channel
  • Clinical Features
  • Normal at birth
  • Onset always after infancy
  • onset may be delayed until adult life
  • can present in 20s
  • begins with weakness of cervical and scapular
    muscles
  • slowly progressive weakness of arm leg neck
    facial muscles
  • exercise intolerance
  • ophthalmoparesis
  • Rare to have ptosis, bulbar dysfunction, leg
    weakness
  • atrophy of affected muscles

53
Slow-Channel Congenital Myasthenic Syndrome
  • Course
  • progresses slowly
  • many patients do not present until after age 10
  • Diagnosis
  • decremental RNS
  • repetitive discharges after nerve stimulation
    (like ChE inhibitor toxicity)
  • muscle Bx type I predominance, group atrophy,
    tubular aggregates, abrnomal end-plate
    configurations

54
Slow-Channel Congenital Myasthenic Syndrome
  • Treatment
  • not effective
  • ChE inhibitors
  • Thymectomy
  • Immunosuppression
  • May be effective
  • Quinidine sulfate improves strength
  • Fluoxetine equally effective

55
Fast Channel Myasthenic Syndromes
  • Pathophysiology
  • Ach receptor/channel complex does not let in
    sufficient sodium
  • Mechanisms
  • Channel open for too short a time
  • Channel takes long time to open up
  • Ach does not bind sufficiently long to receptor
  • Channel requires too much energy to switch from
    inactive to active state
  • Treatment
  • Responds well to 3,4 DAP and anticholinesterases.
  • Ephedrine may help

56
LEMS
  • Epidemiology
  • usually after 40s
  • has been reported in children
  • MF
  • 50 have underlying malignancy (80 of these
    SCLC)
  • Immunopathology
  • antibodies to VGCCs
  • disorganization of motor nerve terminal active
    zone particles
  • SCLC cells contained high concentrations of VGCCs
    and SCLC VGCC are inhibited by LEMS sera
  • Clinical Features
  • Weakness
  • proximal muscles, especially legs
  • oropharyngeal and ocular relatively spared
    (although can be affected)
  • objective weakness mild compared to severity of
    symptoms
  • weakness improves briefly after exercise, then
    returns with sustained activity
  • absent DTR which are enhanced by repeated muscle
    contraction or repeated tapping of tendon
  • can present as prolonged paralysis following use
    of neuromuscular blocking agents in surgery

57
LEMS
  • Clinical Features
  • Autonomic Features
  • dry mouth common
  • impotence
  • postural hypotension
  • Temperature Dependence
  • worse in heat
  • avoid hot showers or baths
  • Diagnosis
  • edrophonium not as effective as seen in MG
  • EMG/NCs most sensitive in distal muscles
  • Neoplastic Workup
  • bronchoscopy
  • PET scan

58
LEMS
  • NCS
  • CMAP amplitudes low
  • Repetitive Nerve Stimulation and Exercise Testing
  • gt10 decrement in CMAP amplitude on slow
    repetitive nerve stimulation (3Hz) between 1st
    and 4th potential
  • gt40 (often gt100) increase in distal CMAP
    amplitude after 10 seconds of maximal voluntary
    exercise.
  • gt40 (oftengt100) increase in distal CMAP
    amplitude after high frequency (30-50Hz)
    repetitive nerve stimulation
  • EMG
  • generally normal
  • motor unit action potentials may be unstable may
    be short, small, or polyphasic (i.e. myopathic)
    may have normal or early recruitment
  • SFEMG
  • increased jitter and blocking

59
LEMS
  • Treatment
  • ChE Inhibitors
  • may work in occasional patients
  • pyridostigmine 30-60mg q6h x several days
  • major benefit is relief of dry mouth
  • Guanidine Hydrochloride
  • increases release of Ach
  • add on agent to mestinon
  • temporary improvement in strength in many
    patients with LEMS
  • start 5-10mg/kg/d div 4-6h apart
  • increase to maximum of 30mg/kg/d q3d
  • SFX
  • BM suppression ,RTA ,Chronic interstitial
    nephritis ,Cardiac arrhythmia ,Hepatic toxicity
    ,Pancreatic dysfunction ,Paresthesiae ,Ataxia
    .Confusion ,Mood changes

60
LEMS
  • Treatment
  • DAP
  • 5-25mg tid-qid
  • facilitates release of Ach from motor nerve
    terminals
  • synergistic with pyridostigmine
  • PLEX and IVIG
  • can provide transitory improvement
  • (Immunosupression ,prednisone,azathioprine
    ,cyclosporine)
  • not as good as in MG
  • Severe Weakness
  • PLEX/IVIG 1st
  • Prednisone and imuran added after improvement
    begins
  • Prognosis
  • variable

61
Botulism
  • Pathophysiology
  • botulinum toxin block release of Ach from motor
    nerve terminal
  • 8 types of toxin
  • types A and B cause most occurrences of botulism
    in US
  • type E transmitted in seafood
  • Clinical Features
  • Course
  • NxVx 1st Sx of food-borne botulism
  • Neuromuscular Sx begin 12-36h after exposure
  • Ocular blurred vision and impaired pupillary
    reflexes
  • Motor weakness and decreased DTRs
  • Autonomic dry mouth ,constipation ,urinary
    retention

62
Botulism
  • Diagnosis
  • Tensilon Test
  • positive in 1/3 of patients
  • do not distinguish botulism from other causes
  • Microbiological
  • Botulinium toxin in stool
  • C. Botulinium culture from stool
  • Wound cultures and serum for Botulinium toxin
  • EMG/NCS
  • reduced CMAP in at least 2 muscles
  • at least 20 facilitation of CMAP amplitude
    during titanic stimulation
  • persistence of facilitation at least 2 minutes
    after activation
  • no postactivation exhaustion
  • SFEMG
  • Jitter and blocking
  • Sensitivity 100 ,Poor specificity

63
Botulism
  • Treatment
  • bivalent (type A, B) or trivalent (A, B, E)
    antitoxin
  • antibiotics NOT effective
  • supportive therapy
  • ChE inhibitors NOT beneficial
  • DAP improves strength but not respiratory
    function
  • Prognosis
  • Most patients make complete recovery within 2-3
    months
  • If sever einvolvement, may not return to normal
    for a year

64
Venoms
  • Clinical Features
  • progressive, symmetrical muscle weakness
  • oculomotor/eyelids most often
  • neck flexion, and pelvic and pectoral girdles
    next
  • bulbar or respiratory if severe
  • cognition and sensation preserved
  • DTR preserved, or minimally diminished
  • Mechanisms
  • initial augmentation of Ach release with
    subsequent depletion
  • facilitation of Ach release without subsequent
    depletion of neurotransmitter
  • depletion of Ach release
  • blockade of post junctional Ach receptor
  • Specific Venoms
  • Funnel Web and Black Widow Spiders (latrodectism)
  • facilitation of neurotransmitter release by
    depolarization of presynaptic terminal

65
Venoms
  • Tick Paralysis
  • Microbiology
  • dermacentor andersoni ,dermacentor variabilis
  • Clincial Features
  • usually children lt5yo
  • similar to GBS
  • ocular motor palsies and papillary abnormalities
    ltGBS
  • Mechanism
  • postsynaptic blockade of neurotoxin
  • Diagnosis
  • CSF protein normal
  • NCS normal or mild slowing of NCV
  • decreased CMAP
  • high frequency RNS may be normal or abnormal
    incremental response
  • Treatment
  • remove tick usually lead to rapid recovery
  • Australian variant may have continued worsening
    for another 1-2 days

66
Other Neurotoxins Affecting The NMJ
  • Marine neurotoxins
  • are rare and come primarily from poisonous fish
    (stonustoxin), a few mollusks (conotoxins), and
    dinoflagellates.
  • Heavy metal intoxication
  • is a rare cause of neuromuscular toxicity.
  • Ingestion of contaminated grain used for flour in
    bread.
  • produced weakness with characteristic
    decremental responses
  • partial reversal with ChE inhibitors.
  • Organophosphates
  • impair neuromuscular transmission by irreversibly
    inhibiting acetylcholinesterase.
  • producing a depolarizing neuromuscular block.

67
Neuromuscular Junction Disorders
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