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Neuromuscular Disorders: disorders of neuromuscular junction, motor neuron, and muscle


... late in the course of disease with severe bulbar symptoms and marked generalized weakness Myasthenia Gravis Disease course marked by exacerbations and ... – PowerPoint PPT presentation

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Title: Neuromuscular Disorders: disorders of neuromuscular junction, motor neuron, and muscle

Neuromuscular Disorders disorders of
neuromuscular junction, motor neuron, and muscle
  • Kasia Petelenz
  • Greg Gordon (and others)
  • November 15, 2005

Myasthenia Gravis
  • Incidence 110,000 to 130,000
  • Women 20 30 years of age are most often
    affected men older than 60 display symptoms
  • Acquired chronic autoimmune disorder
  • Hallmarks are weakness and rapid exhaustion of
    voluntary skeletal muscles

Myasthenia Gravis
  • Muscle strength characteristically improves with
    rest, deteriorates rapidly with exertion
  • Skeletal muscle atrophy is unlikely
  • Laryngeal and pharyngeal muscle weakness may lead
    to aspiration, problems clearing secretions,
    difficulty chewing.

Myasthenia Gravis Presentations
  • Clinical Classification
  • Class 1 ocular symptoms only
  • Class 1A ocular symptoms with EMG evidence of
    peripheral muscle involvement
  • Class 2A mild generalized symptoms
  • Class 2B more severe and rapidly progressive
  • Class 3 acute and presenting in weeks to months
    with severe bulbar symptoms
  • Class 4 late in the course of disease with
    severe bulbar symptoms and marked generalized

Myasthenia Gravis
  • Disease course marked by exacerbations and
  • Infection, stress, surgery, pregnancy have
    unpredictable effects, but often cause
  • Antibiotics can aggravate weakness
  • Diseases considered AI in origin often coexist
  • Decreased thyroid function
  • RA
  • SLE
  • Pernicious Anemia

Mechanism - MG
  • Decrease in functional Acetylcholine receptors at
    the nicotinic neuromuscular junction
  • 70 - 90 have circulating antibodies to AChRs
  • Neonatal
  • Transient born to mothers with MG Abs cross
  • Only 12 symptomatic

(No Transcript)
Therapy - Myasthenia Gravis
  • Immunosuppressants
  • Steroids - Commonly cause dose dependent weakness
  • Azathioprine,Cyclosporine
  • Plasmapheresis, iv immunoglobulin
  • Acute exacerbations, i.e. in immediate
    post-operative period if anticholinesterases have
    been withheld and symptoms are severe
  • Plasmapheresis IVIG for 5 days -gt rapid
    improvement, may last for weeks
  • Thymectomy

Important part of Rx
  • Anticholinesterase drugs
  • Pyridostigmine, po duration of 2-4 hours
  • Excessive administration -gt Cholinergic Crisis
  • SLUDGE Salivation, lacrimation, urination,
    defecation, miosis bradycardia bronchospasm
  • Profound weakness due to excess Ach at NMJ -gt
    persistent depolarization
  • Treatment of Cholinergic Crisis Atropine,
    Mechanical Ventilation if needed

Anesthetic Concerns - MG
  • Pre-op Predictors of Need for Post-Operative
    Ventilatory Support
  • Disease duration gt 6 years
  • Concomitant pulmonary disease
  • Maximum inspiratory force (MIF) lt-25cm H2O
  • VC lt 4 mL/kg
  • Pyridostigmine dose gt750 mg/day

Anesthetic Considerations
  • Old School Recommended to d/c anticholinesterase
    if pt has only mild weakness
  • Theory Potentiates Sux, inhibit effect of NDMRs
  • Pts more susceptible to vagal arrhythmias
  • Slows metabolism of ester LAs, Sux, Mivacron
  • New School No experimental evidence to suggest
    that altering a pts anticholinesterase regimen
    has any clinically significant effect on NMB or
    duration of mechanical ventilation post-op.

Anesthetic Considerations
  • Increased risk for aspiration
  • Premed with Reglan/Ranitidine
  • Reduced respiratory reserve
  • Avoid premeds with opioids, benzos
  • Pts are very sensitive to respiratory depressant

Anesthetic Considerations - MG
  • Response to Sux is unpredictable
  • Relative resistance usually seen
  • ED95 approximately 2.6 x normal
  • Exquisitely sensitive to NDMRs!!
  • All NDMRs have been used successfully and
    uneventfully if twitches are monitored
  • Should be titrated in 1/10 to 1/20 normal dose
  • Sensitivity to NMDRs is increased during
    co-administration of potent inhaled anesthetic
  • Reverse with standard doses of anticholinesterase
    and anti-cholinergic

Post-Op Considerations MG
  • Case Scenario Pt extubated in OR, 40 minutes
    later c/o feeling weak and unable to breathe
  • Myasthenic crisis decreased response to
  • Cholinergic crisis overdose of
  • Both increases in muscle weakness, salivation,
    and sweat occur

Post-Op Anesthetic Considerations Myasthenia
  • Differentiate with response to 10mg iv
  • Myasthenic crisis shows some improvement in
    muscle strength
  • Cholinergic crisis shows no increase in muscle
    strength and worsening of respiratory distress.

MG upstairs
  • Epidural Analgesia preferred
  • Maintains SV and LA dose can be easily titrated
  • No evidence that MG pts are more sensitive to LA
    used for conduction anesthesia, but MG
    predisposes to increased weakness
  • Amide LAs probably better
  • Hepatic Metabolism
  • Not hydrolyzed by serum cholinesterases
  • Emergent C/S
  • Sux to allow rapid control and protection of

Lambert-Eaton Syndrome
  • Mimics Myasthenia Gravis
  • Most often affects older males
  • Usually associated with Small Cell CA (lung)
  • Voltage increment to repeated stimulation and a
    poor response to anticholinesterases
  • Sensitive to NMDRs, normal/increased response to
  • Antibodies to Ca channel associated protein
    synaptogamin present

Motor Neuron Diseases
  • Degeneration of upper and/or lower motor neurons
  • i.e. Amyotrophic Lateral Sclerosis
  • Muscular weakness and atrophy
  • Steady, asymmetric progression
  • Sensory systems, voluntary eye movements, and
    urinary sphincters are spared

Amyotrophic Lateral Sclerosis
  • Progressive neuromuscular disorder
  • Characterized by degeneration of spinal motor
    neurons, leading to
  • Denervation
  • Muscle wasting
  • Paralysis
  • Eventually death, most often secondary to
    respiratory failure

ALS Anesthetic Concerns
  • Increased Sensitivity to NDMRs
  • Reduction in choline acetyltransferase (involved
    in synthesis of ACh) occurs secondary to
    degeneration of anterior horn cells
  • Avoid Sux
  • Hyperkalemic response in degenerating muscles

ALS Anesthetic Concerns
  • GA documented to cause ventilatory depression
    post-operatively, even without use of muscle
  • Respiratory complications are common and a major
    cause for concern
  • Regional relatively contraindicated in pts with
    motor neuron disease, including ALS, for the fear
    of exacerbating the disease

ALS Case Description
  • 76 y/o with rapidly progressing ALS, s/p femoral
    head fx
  • PE siallorrhea, dysarthria, dysphonia, cachexia
  • Recent PFTs reveal 20 nL lung function
  • Refused to withdraw Do not intubate orders for
    the intra and post-op time frames

Intra-Op Course
  • Intrathecal Catheter placed at L3/4
  • 0.25 mL of Bupivicaine 0.75 (1.9 mg) injected
    through catheter
  • T8 level
  • Catheter was discontinued upon completion of case
  • POD 1 minor desats, resolved with O2 therapy
  • No c/o HA during post-op course

Choice of most minimally invasive anesthetic
  • Case reports have documented successful use of
    epidural anesthesia
  • Gradual onset of block
  • Less hemodynamic instability
  • But inadequate epidural anesthesia may result
  • Incremental Intrathecal technique allowed
    adequate anesthesia without adverse hemodynamic
    consequences, and enabled extension of block as

Disorders of Muscle
  • Congenital Muscular Dystrophies
  • Myotonic
  • Duchenne, Becker
  • Acquired Myopathies
  • Cushings Syndrome
  • Dermatomyositis
  • Polymyositis

Myotonic Dystrophy
  • Characterized by persistent contractures of
    skeletal muscles after voluntary contraction or
    following electrical stimulation
  • Peripheral nerves and NMJ are not affected.
  • Abnormality in the intracellular ATP system that
    fails to return calcium to the sarcoplasmic
  • Contractures are not relieved by NDMRs, regional
    or deep anesthesia
  • Infiltration of LA into skeletal muscle may
    induce relaxation
  • Depression of rapid sodium flux into muscle cells
    by phenytoin, procainamide, quinidine, may
    alleviate contracture by delaying membrane

Characteristic Appearance - MD
Coexisting Organ Dysfunction - MD
  • Cardiac Involvement
  • Mitral valve prolapse 20 of individuals
  • Deterioration of the His-Purkinje system lead to
  • 1st degree AV block very common
  • Pulmonary Pathology
  • Restrictive lung disease
  • Impaired responses to hypoxia and hypercarbia

Coexisting Organ Dysfunction - MD
  • Cataracts very common
  • GI abnormalities
  • Gastric atony
  • Intestinal hyper-motility
  • Pharyngeal muscle weakness with impaired airway
  • Cholelithiasis

Anesthetic Pre-Op Concerns
  • Eventually develop extremely compromised
    respiratory function
  • Pulmonary Aspiration, Pneumonia
  • Chronic Alveolar hypoventilation because of
    impaired neuromuscular function -gt chronic
  • Decreased FRC, VC, MIP
  • Avoid premeds very sensitive to respiratory
    depressant effects of narcotics and benzos

Anesthetic Concerns MD
  • Avoid Etomidate
  • May cause myoclonus and precipitate contractures
  • Avoid Sux
  • Produces an exaggerated contracture
  • Susceptible to MH
  • Avoid Anticholinesterases may precipitate
    contracture by increasing ACh available at NMJ
  • Keep room warm shivering may lead to

Anesthetic Concerns MD
  • Exaggerated effects of myocardial depression from
    inhaled agents- even Asymptomatic pts have some
    degree of cardiomyopathy
  • Anesthesia and surgery could theoretically
    aggravate co-existing cardiac conduction blockade
    by increasing vagal tone or causing transient
    hypoxia of the conduction system
  • Pregnancy
  • Exacerbation of symptoms is likely
  • Uterine atony and retained placental often
    complicate vaginal delivery

Guillaume Benjamin Amand Duchenne
  • The French neurologist, who studied and defined
    many neuromuscular diseases, in the mid 1900s,
    including the one named for him

Completely irrelevant side note
  • Duchenne investigated facial expression in a
    crude but effective manner of shocking the
    facial muscles using galvanic current defined
    facial expressions

Duchenne Muscular Dystrophy
  • Most common muscular dystrophy encountered by
  • Incidence 13,500 live male births
  • Characterized by painless degeneration and
    atrophy of skeletal muscles
  • X-linked disorder
  • DMD gene isolated to short arm of the X
    chromosome at position 21
  • Estimated mutation rate is one of the highest for
    any human disease

Duchenne Muscular Dystrophy
  • DMD gene product dystrophin
  • Absent or nonfunctional in DMD patients
  • Associated with muscle cell membranes
  • In its absence, a sequence of events occurs that
    leads to calcium influx into the muscle cells -gt
    cell degeneration and death
  • Affects Skeletal, Cardiac, and Smooth muscle

  • Progressive disease course

DMD Disease Progression
  • Under 2 yrs old
  • Behave like healthy toddlers
  • 2-5 yrs old
  • First outward signs of muscular weakness
  • Clumsiness, frequent falling, waddling gait,
    difficulty climbing stairs
  • Calf muscles begin to look enlarged
  • 6-12 yrs old
  • Child walks on toes secondary to Achilles tendon
    tightening and to compensate for weak quads
  • Weakening pelvic and shoulder girdles -gt
    compensatory lordosis

Gowers Maneuver
DMD Disease Progression
  • 8-14 yrs old
  • Lose ability to walk
  • Decrease in caloric requirements -gt even normal
    diet leads to obesity
  • 95 develop scoliosis
  • Adult phase
  • Scoliosis weakened respiratory muscles,
    inactivity, obesity -gt compromised lung expansion
    and function
  • Vital capacity decreased approximately 50
  • Weak cough -gt vulnerable to pneumonia
  • Late 20s
  • 90 die of respiratory complications, 10 cardiac

Cardiopulmonary Dysfunction
  • Degeneration of cardiac muscle inevitable
  • Tall R waves in V1 deep Q waves in limb leads
    short PR intervals sinus tach
  • MR due to papillary muscle dysfunction
  • Decreased cardiac contractility
  • Pulmonary difficulties
  • Chronic weakness predisposes to decreased ability
    to cough, leads to accumulation of secretions -gt
  • Sleep apnea common -gt pulmonary hypertension

Case Report DMD, PEG, and LMA
  • 20 yr old with DMD
  • Chronic Respiratory Failure
  • Vital Capacity 450 mL (9 predicted)
  • Maximum inspiratory and expiratory pressures -20
    and 5 cm H2O
  • To generate effective cough MEP gt60
  • Cough peak flow of 40 L/min
  • Cough lt160 L/min associated with ineffective
    airway clearance
  • On 24 hr nasal BiPAP, settings 20/7, rate 16

Case Report DMD, PEG, and LMA
  • CHF
  • LVEF 20
  • Physical Exam
  • hypertrophied tongue
  • MP III
  • muscle strength 1-2/5 upper and lower extremities

Case Report DMD, PEG, and LMA
  • Procedure performed in PACU
  • Standard monitors
  • Premed 1mg Midazolam, just prior to induction
  • Induction
  • 300mcg/kg/min Propofol, adj for maintenance as
  • 30 mg Ketamine
  • SV with NPPV until eyelash reflex abolished

Case Report DMD, PEG, and LMA
  • Appropriate LMA inserted
  • Well lubricated gastroscope passed through the
    mouth, behind LMA
  • LMA deflated as necessary to allow better scope
  • Ventilation assisted as needed to maintain PaCO2
  • LMA removed after procedure under deep sedation
    with spontaneous ventilation, and NPPV replaced
  • PICU monitoring overnight, d/c home lt 24 hours

(No Transcript)
Why this type of anesthetic?
Anesthesia Concerns with DMD
  • Lingular hypertrophy difficult intubation
  • Association with MH has been suggested but not
  • But, avoid volatile agents if possible, and keep
    Dantrolene available

Anesthesia Concerns with DMD
  • NDMRs ok, but action is prolonged
  • Regenerating muscle fibers, common in DMD until
    at least 8 years of age, are considered to be
    more vulnerable to the effects of SUX
  • Difficult Extubation
  • Endotracheal edema
  • Mucosal congestion
  • Inability to clear retained secretions
  • Acute respiratory failure

Review Questions (Hall)
  • 173. Which of the following diseases is
    associated with increased resistance to
    neuromuscular blockade?
  • A. Myasthenia Gravis
  • B. Myasthenic Syndrome
  • C. Huntingtons chorea
  • D. Duchenne muscular dystrophy

Answer A
  • Myasthenia Gravis
  • Fewer AChRs.
  • Resistant to Sux.
  • Sensitive to NMDRs.
  • Myasthenic Syndrome (Eaton Lambert)
  • Decreased release of Ach but normal number of
  • Sensitive to Sux and NMDRs
  • Huntingtons chorea
  • Decreased plasma cholinesterase activity
  • Prolonged response to Sux
  • Duchenne Muscular Dystrophy
  • Sux is relatively contraindicated
  • NMDRs have a normal response, although patients
    have prominent skeletal muscle weakness.

Review Questions (Hall)
  • 489. 37 y/o male with myasthenia gravis, to ED,
    confused, agitated, 2 day h/o weakness, SOB. RR
    30 breaths/min, TV 4mL/kg.
  • ABG PaO2 60 PaCO2 51 HCO3 -25 pH 7.3
    SaO2 90
  • Edrophonium 5mg iv -gt TV 2mL/kg
  • A. Tracheal Intubation and Mechanical Ventilation
  • B. Repeat Edrophonium
  • C. Neostigmine 1 mg IV
  • D. Emergency Trach
  • E. Atropine 0.4 mg IV

Answer A
  • Cholinergic crisis vs. myasthenic crisis
  • Cholinergic crisis worsens with administration of
  • Pt should be electively intubated until strength

Review Questions (Hall)
  • 669. A lumbar epidural is placed in a 24 y/o G1P0
    with myasthenia gravis. Select the true
    statement regarding neonatal MG.
  • A. The newborn is usually affected.
  • B. The newborn is affected by maternal IgM
  • C. The newborn may require anticholinesterase
    therapy for up to 3 weeks
  • D. The newborn will need lifelong treatment
  • E. Only female newborns are affected

Answer C
  • IgG antibodies are directed against AChRs
  • IgG can cross placenta
  • Neonatal MG is characterized by muscle weakness
    (hypotonia, respiratory difficulty)
  • Presents within the first 4 days of life (80
    within first 24 hours)
  • Anticholinesterase therapy may be required until
    the maternal IgG is metabolized

  • Bach JR, Ishikawa Y, Kim H. Prevention of
    Pulmonary Morbidity for patients with Duchenne
    Muscular Dystrophy. Chest 19971121024-28
  • Benumoff JL, ed. Anesthesia Uncommon Diseases,
    4th Ed. Philadelphia WB Saunders. 9, 373-4
  • Brimacombe J, Newell S, Bergin A, et al. The
    Laryngeal Mask for Percuatneous Endoscopic
    Gastrostomy. Anesth Analg 200091635-6
  • Dillon FX. Anesthesia issues in the perioperative
    management of myasthenia gravis. Semin Neurol.
    2004 Mar24(1)83-94.
  • Faust RJ, ed. Anesthesiology Review, 3rd Ed.
    Philadelphia Churchill Livingstone. 490-494
  • Hara K, Sakura S, Saito Y, et al. Epidural
    Anesthesia and Pulmonary Function in a Patient
    with Amyotrophic Lateral Sclerosis. Anesth Analg

  • Morris P. Duchenne Muscular Dystrophy a
    challenge for the anaesthetist. Paediatric
    Anaesthesia 199761-4
  • Moser B, Lirk P, Lechner M, et al. General
    anaesthesia in a patient with motor neuron
    disease. Eur J Anesthes 200421921-922
  • Otsuka N, Igarashi M, Shmiodate, et al.
    Anesthetic management of two patients with
    amyotrophic lateral sclerosis. Masui. 2004
  • Pope JF, BirnKrant DJ, et al. Noninvasive
    Ventilation during percuatneous gastrostomy
    placement in Duchenne Muscular Dystrophy. Pediatr
    Pulmonol 199723468-471
  • Stoelting RK, Dierdor SF, ed. Anesthesia and
    Co-Existing Disease, 4th Ed. Philadelphia
    Churchill Livingstone. 217,517-519,522-528
  • Yao FS, ed. Anesthesiology Problem-Oriented
    Patient Management, 5th Ed. Philadelphia
    Lippincott Williams Wilkins.1019-1032