Neuromuscular Junction Disorders - PowerPoint PPT Presentation

View by Category
About This Presentation

Neuromuscular Junction Disorders


Neuromuscular Junction Disorders ... allowing weaning from ventilation episodes may persist throughout infancy and even into adulthood sudden bouts of respiratory ... – PowerPoint PPT presentation

Number of Views:1163
Avg rating:3.0/5.0
Slides: 68
Provided by: AlSa8
Learn more at:


Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Neuromuscular Junction Disorders

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

Neuromuscular junction

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

  • 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.

  • The MuSK
  • maintains the normal functional integrity of the
  • 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.

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

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

Clinical presentation
  • most commonly presents with weakness of
    extraocular muscles ptosis and/or diplopia, /-
  • can mimic any pattern of ophthalmoplegia
    including pupil sparing IIIrd nerve palsy,
    internuclear ophthalmoplegia (INO) or sixth nerve
  • 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

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

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

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

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

(No Transcript)
(No Transcript)
Diagnostic Procedures

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

Tensilon test
Antibodies Against Acetylcholine Receptors
  • Value
  • confirm diagnosis but cant predict severity
    neither predict thymoma
  • Test Characteristics
  • 80 sensitivity for generalized myasthenia (range
  • 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

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

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

Repetitive nerve stimulation
  • (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
  • 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

(No Transcript)
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
(No Transcript)
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

(No Transcript)
  • Cholinesterase Inhibitors
  • Roles
  • diagnostic
  • early, symptomatic treatment
  • adjunct to immunomodulatory and immunosuppressive
  • 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

  • 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

  • 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

  • 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
  • used in ocular myasthenia

  • Taper
  • decrease to lowest dose necessary to maintain
  • 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

(No Transcript)
  • 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

  • Azathioprine
  • severe allergic reaction (required
  • 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
  • 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)

  • 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

  • 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

  • Mycophenolate Mofetil
  • Mechanism
  • Selectively inhibits proliferation of B- and T-
    lymphocyte clones responding to antigenic
  • 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
  • Side Effects
  • Diarrhea
  • leukopenia

Plasma Exchange
  • Roles
  • sudden worsening of myasthenic symptoms for any
  • 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

  • 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.

  • Other Types Of Myasthenia Gravies

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
  • 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

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

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
  • More involvement of neck, shoulder, respiratory
  • Less limb
  • More bulbar
  • Increased risk of myasthenic crisis in 1st 2
  • 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

Genetic Myasthenic SyndromesCongenital
  • 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
  • Reduced end plate acetylcholinesterase
  • Impaired AChR function

Genetic Myasthenic SyndromesCongenital
  • 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

Genetic Myasthenic SyndromesCongenital
  • 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
  • Treatment
  • ChE inhibitors improve limb weakness in many
  • Ocular muscle weakness less responsive
  • Some children respond to DAP

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

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

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
  • slowly progressive weakness of arm leg neck
    facial muscles
  • exercise intolerance
  • ophthalmoparesis
  • Rare to have ptosis, bulbar dysfunction, leg
  • atrophy of affected muscles

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

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

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

  • Epidemiology
  • usually after 40s
  • has been reported in children
  • MF
  • 50 have underlying malignancy (80 of these
  • 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
  • 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

  • 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

  • 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
  • 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
  • increased jitter and blocking

  • 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

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

  • 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
  • Motor weakness and decreased DTRs
  • Autonomic dry mouth ,constipation ,urinary

  • 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
  • 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
  • Jitter and blocking
  • Sensitivity 100 ,Poor specificity

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

  • Clinical Features
  • progressive, symmetrical muscle weakness
  • oculomotor/eyelids most often
  • neck flexion, and pelvic and pectoral girdles
  • 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

  • Tick Paralysis
  • Microbiology
  • dermacentor andersoni ,dermacentor variabilis
  • Clincial Features
  • usually children lt5yo
  • similar to GBS
  • ocular motor palsies and papillary abnormalities
  • 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

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

Neuromuscular Junction Disorders