Neuromuscular Emergencies

1
Neuromuscular Emergencies

• Hanni Bouma
• R3 Neurology

2
Outline

• Approach to neuromuscular respiratory failure
• Signs Symptoms
• Investigations
• Knowing when (to ask someone else) to intubate
• Overview of
• Myasthenic crisis
• GBS
• Botulism

3

• True or false? Regarding GBS
• 10 of pts will require intubation.
• All cases of suspected GBS should be treated with
  either IVIG or PLEX.
• Normal CSF protein precludes the diagnosis.
• Hypertension is the most common autonomic
  complication.

4
Case 1

• A 32-yo M with MG since age 20, on stable dose of
  pred 40, Imuran, and Mestinon, is admitted to
  hospital for elective bowel surgery
  (complications of diverticulitis)
• Pt. has persistent diplopia and mild fatigable
  weakness at the deltoids
• The surgery team calls you the morning of his
  scheduled surgery to ask if they should do
  anything for his myasthenia.

5
Case 1

• You should
• A) Suggest switching to equivalent dosage of IV
  steroids while NPO
• B) Review med list advise re drugs that might
  trigger a crisis (ie. Antibiotics!!)
• C) Kindly recommend postponing the surgery for
  pre-op IVIG or PLEX
• D) All of the above

6
Case 2

• A 10-month-old infant presents with constipation
  and poor feeding followed by progressive
  hypotonia, descending weakness, dilated pupils,
  and bilateral ptosis.
• What is the likely diagnosis?
• How was it likely acquired?
• How would you treat him?

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Case 3

• You are called to see a patient in ICU with known
  diagnosis of MG, recurrent crises leading to ICU
  admissions, on stable dose of pred 60 mg qd and
  Imuran. Admitted with MG crisis, intubated then
  trached. Now, 2 weeks later, doing better as
  per ICU. They want to start tapering his
  prednisone. What do you advise them to do?

8
Case 3

• 1) Agree with their plan to begin a slow tapering
  course by 10 mg qweek initially.
• 2) Discuss the patient with their treating
  neurologist.
• 3) Advise them to avoid rapid tapering of
  steroids given the risk of recurrent crisis.
• 4) Both 2 3.

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Part 1 Neuromuscular Respiratory Failure
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Respiratory Failure Basics

• Type I Hypoxia without hypercapnia
• Usually associated with ? WOB
• V/Q mismatch most common
• Vascular disease/shunts (PE, Pulm. HTN, R-gtL
  shunts)
• Interstitial lung disease (ARDS, cardiogenic
  pulmonary edema, pneumonia)
• Pneumothorax, atelectasis

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• Type II Hypercapnia with or w/o hypoxia
• A.k.a. hypoventilation
• Neuromuscular conditions
• Deformities (kyphoscoliosis)
• Reduced breathing effort (extreme obesity, drug
  effects, brainstem lesion affecting respiratory
  drive)
• Increased airway resistance (asthma, COPD)

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Neuromuscular Causes

• Spinal cord lesion
• Cervical cord compression, transverse myelitis
• Motor neuron lesion
• ALS
• Peripheral nerve lesion
• GBS, CIDP, critical illness polyneuropathy, Lyme
  disease, tick paralysis, toxic
• NMJ disorder
• MG, LEMS, botulism, organophosphate poisoning
• Muscle lesion
• Polymyositis, dermatomyositis, critical illness
  myopathy, hyperthyroidism, congenital myopathy
  (muscular dystrophy), mitochrondrial myopathy

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History

• Time course?
• progressive weakness over hours to days ? GBS
• fluctuating weakness (on an hourly basis) present
  for weeks/months ? MG
• Distribution of weakness?
• Proximal gt distal (MG GBS)
• Ascending in GBS
• Sensory Sx.?
• Distal paresthesias common in GBS
• No sensory invt in MG

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History

• FH?
• Pain?
• Low backache frequently in GBS neck pain
  C-spine lesion?
• Antecedent illness?
• 60 of GBS triggered by viral URT illness or
  C.jejuni gastro
• 40 of myasthenic crises triggered by infection
• Medications
• Exposure to fertilizers pesticides?
• Organophosphate poisoning
• Recent diet
• Botulism from home-canned goods

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Exam

• Long, thin face? (myotonic dystrophy?
  Congenital?)
• Skin rash (dermatomyositis?
• CNs
• Pupils
• Reactivity may be lost in botulism or
  Miller-Fisher variant of GBS
• EOM
• Opthalmoparesis or ptosis (MG? mitochondrial D/O?
  MFS?)
• Presence or absence of bulbar weakness?
• Motor exam
• Fasciculations? (ALS, organophosphate poisoning)
  tone power (fatigable weakness? Distribution
  proximal vs. distal?)

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Exam

• Sensory
• Normal in MG
• Distal sensory loss in GBS, esp vib/prop
• Sensory level at C-spine level w/ quadriparesis
  C-spine lesion
• Coordination
• Ataxia in MF variant of GBS
• Reflexes
• Areflexia in GBS preserved in MG

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Mechanisms

• 1) Bulbar dysfunction
• Facial, oropharyngeal, laryngeal weakness ? upper
  airway obstruction in supine position
• Impaired swallowing ? aspiration
• 2) Inspiratory muscle weakness/diaphragmatic
  paralysis? atelectasis ? V/Q mismatch ? hypoxia
• 3) Expiratory muscle weakness ? hypoventilation
  AND weak cough/poor secretion clearance ?
  aspiration, pneumonia
• 4) Acute complications ? PE

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Symptoms

• If subacute (ie. GBS) dyspnoea and orthopnoea
• Easy to overlook
• If gradual onset, inadequate respiration usually
  occurs first during sleep
• Symptoms of nocturnal hypoventilation
• a broken sleep pattern, nightmares, nocturnal
  confusion, morning headache, daytime fatigue,
  mental clouding and somnolence.
• SOBOE less common in NMDs than in those with
  other Cardioresp D/O (reduced mobility)
• Dyspnoea when lying flat or immersed in water
• suggests weakness of the diaphragm

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Warning signs

• Rapid, shallow breathing
• Stridor
• Bulbar weakness
• weak cough, nasal voice, pooling of saliva
• Orthopnea
• Staccato speech
• Abdominal paradox
• http//www.youtube.com/watch?vRFGzdNFuXIM
• Weakness of neck trapezius muscles
• Single-breath count

Mehta, S. Neuromuscular disease causing acute
respiratory failure. Respiratory Care, 2006. 51
(9) 1016-1023.
20
Investigations

• Bedside PFTs 20/30/40 rule
• Vital capacity (max exhaled volume after full
  inspiration). Normal 60 ml/kg (4 L in 70 kg
  person). VC lt 20 ml/kg (or 1 L) means intubation
• Max inspiratory pressure. Index of ability to
  avoid atelectasis. Normal gt 80 cm H2O (male),
  gt70 cm H2O (female). MIP gt-30 means intubation
• Max expiratory pressure. Index of ability to
  cough/clear secretions. Mean MEP 140 cm H2O
  (male), 95 cm H20 (female). MEP lt40 means
  intubation

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Investigations

• ABG
• Hypercarbia (PCO2 gt 45 mmHg)
• PCO2 often normal or low until late in NM resp
  failure
• Established resp failure from NMDs low pO2,
  normal pH, elevated bicarb pCO2
• Elevations of bicarb pH with normal pO2 pCO2
  suggest nocturnal hypoventilation
• Hypoxia (PO2 lt 75 mmHg) usually atelectasis or
  pneumonia in acute setting
• Basic labs (CBC, SMA-10, LFTs, CK)
• CXR

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Predictors of need for MV

• 20/30/40 rule
• or reduction in VC, MIP, MEP by gt30
• PO2 lt70 mmHg on RA or PCO2 gt50 mmHg w/ acidosis
• Dysarthria, dysphagia, impaired gag reflex

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Intubation things to think about

• Code status?
• Call ICU if signs of imminent resp failure
• Identify early to avoid emergency
  intubationelective intubation always preferred
• Minimizes atelectasis/pneumonia
• Minimizes complications of intubation specific to
  NMDs
• Avoid depolarizing NM blockers

24
NPPV?

• Few studies on its use in GBS MG
• Inappropriate if upper airway function severely
  impaired
• More often used in chronic NMDs (ALS, muscular
  dystrophies) for chronic hypoventilation

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General care

• Serial PFTs (MIP/MEP/FVC) bid to qid
• Electrolytes low potassium, high magnesium low
  phosphate ? exacerbate muscle weakness
• Chest physio, suctioning incentive spirometry
• DVT prophylaxis
• HOB elevation
• NPO if bulbar weakness NG or Dobhoff feeding

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Part 2MGGBSBotulism
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MG

• Ab-mediated attack on nicotinic Ach rec ?
  defective transmission across NMJ
• Bimodal F 20-30 yo M 50-60 yo
• 2 autoimmune forms
• Ach receptor Ab 80 with generalized MG 50
  with ocular MG
• Anti-MuSK Ab 50 of patients who are Ach rec Ab
  negative typically female with prominent bulbar
  weakness

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Presentation

• Motor
• Fluctuating, fatigable weakness involving eyes
  (90), face/neck/oropharynx (80), limbs (60)
• Limbs rarely affected in isolation
• Rest restores strength (at least partially)
• Sensory normal
• Reflexes preserved
• Thymic abnormalities
• Malignant thymoma in 10-15 (more severe disease)
• Thymic hyperplasia in 50-70

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Investigations

• Ach receptor Abs
• Anti-MuSK Abs
• Edrophonium (Tensilon) test obsolete
• EMG
• Repetitive nerve stimulation gt10 decrement in
  amplitude betw 1st 5th CMAP
• Single-fiber jitter
• Sens gt95 for MG but not specific

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Management general

• Symptomatic therapy (mild-moderate weakness)
• Cholinesterase inhibitors (Mestinon)
• Short-term disease suppression
• To hasten clinical improvement in hospitalized
  pts w/ crisis or impending crisis
  pre-operatively chronic refractory disease
• PLEX or IVIG
• Long-term immunosuppression
• When weakness is inadequately controlled by
  Mestinon
• Prednisone
• Azathioprine (if steroid failure or excessive SE)
• Cyclosporine, Mycophenolate mofetil

31
Myasthenic Crisis

• Defined by resp failure requiring ventilatory
  assistance
• Occurs in 20-30 mortality 5
• Common precipitants
• Infection in 40 (esp respiratory)
• Medications
• Surgery
• Pregnancy
• Aspiration

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Drugs that exacerbate MG

• Antibiotics (Penicillins like Tazocin are OK!)
• Aminoglycosides (genta, tobra)
• Fluroquinolones (cipro)
• Macrolides (erythromycin, azithro, tetracycline,
  doxycycline)
• Cardiac
• All beta-blockers
• Calcium channel blockers
• Anticonvulsants
• Phenytoin, CBZ

• Antipsychotics, lithium
• Thyroid hormones
• Magnesium toxicity
• Iodinated contrast agents
• Muscle relaxants
• Baclofen
• Long-acting benzos
• Too much anticholinesterase

33
Myasthenic crisis management

• General
• Determine if resp failure is imminent!!
• Stop any meds that may be contributing
• Mestinon usually stopped as well
• May contribute to increased airway secretions in
  intubated patients
• Treat any infection

34
Myasthenic Crisis management

• Specific
• PLEX or IVIG
• start one or the other, quickly
• Comparable efficacy
• Evidence somewhat limitedTBD later
• Earlier response seen with PLEX, but more adverse
  events
• Preference somewhat individualized

35
Myasthenic crisis management

• PLEX
• Removal of anti AChR and antiMuSK Abs
• 1 session/day x 5
• No superiority of PLEX qd x 5 vs qod x 5
• Rapid onset of action (3-10 days)
• Need central line with associated complications
• PTX, hemorrhage, line sepsis
• Caution in pts with sepsis, hypotension may lead
  to increased bleeding and cardiac arrhythmias

36
Myasthenic crisis management

• IVIG
• 0.4g/kg/day x 5 days
• Easily administered and widely available
• Long duration of action
• May last as long as 30 days
• Side effects
• Anaphylaxis in IgA deficiency
• Renal failure, pulmonary edema
• Aseptic meningitis
• Thrombotic complications and stroke

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Myasthenic crisis management

• Therapeutic effect of PLEX IVIG is
  short-livedlasts weeks
• Therefore, glucocorticoids started at high dose
  (60 to 80 mg qd) as well
• Onset of benefit at 2-3 wks, peaks at 5.5 mos
• Initiation assd with transient worsening of
  weakness, serious in up to 50
• Occurs 5-10 days after initiation lasts 5-6
  days
• Resp failure requiring MV in up to 10
• Concomitant use of PLEX or IVIG helps to prevent
  this transient worsening

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GBS

• Most common cause of acute or subacute gend
  paralysis
• Monophasic AIDP autoimmune attack against
  surface antigens on peripheral nerves
• Develops 5 days to 3 weeks after resp/GI
  infection in 60
• Campylobacter jejuni (26)
• Viral URTI, influenza
• EBV, CMV, VZV, HIV, hep A B, coxsackie
• Other precipitants immunization, pregnancy,
  surgery, Hodgkins disease

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Presentation

• Sensory
• distal paresthesias/numbness (earliest Sx.)
• Reduced vibration/proprioception
• Motor
• Symmetric evolves over days to 1-2 wks
• Ascending LE before UE proximalgt distal
• Reflexes reduced, then absent
• Autonomic instability
• Other low backache very common, myalgias

40
Investigations

• NCS/EMG
• Reduced conduction velocities
• Loss of F waves
• Conduction block in motor nerves
• Reduced motor amplitudes 2 axonal damage ?
  worse Px.
• CSF
• High protein (may be normal in first 2 days)
• No cells or few lymphs
• 10 have 10-50 lymphs

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Management

• Admit for observation (potential for
  deterioration)
• Determine if resp failure imminent
• IVIG (0.4g/kg/d x 5 d) or PLEX (4-6 Rx. q1-2d)
• Equally effective (2012 AAN guideline)
• PLEX useful in first 2 weeks benefit less clear
  after thatalso more adverse effects
• Steroids no proven benefit

42
Predictors of need for MV in GBS

• Time from onset to admission lt 7 days
• Inability to cough
• Inability to stand
• Inability to lift elbows or head
• LFT increases
• Presence of autonomic dysfxn

Sharshar T, Chevret S, Bourdain F, Raphael JC.
Early predictors of mechanical ventilation in
Guillain-Barre syndrome. Crit Care Med
200331(1)278283.
43
Course

• Progression over 1-4 weeks
• Recovery few wks to months
• Mortality 3-5
• Poor prognosis
• Resp failure requiring intubation
• Advanced age
• Very low distal motor amplitudes (axonal damage)
• Rapidly progressive weakness over 1 week

44
Botulism

• Toxin is a presynaptic blocker of Ach release
• Onset of Sx. 12-36 hours after ingestion
• Prodrome N/V, abdo pain, diarrhea, dry mouth
• Symmetric neurologic deficits
• First develop acute cranial neuropathies
  (opthalmoplegia, can be total B/L ptosis,
  dysphagia, dysarthria, facial weakness)
• Blurred vision secondary to pupillary dilatation
• Descending muscle weakness
• No sensory deficits apart from blurred vision
• Urinary retention/constipation (smooth muscle
  paralysis)
• Respiratory failure is primary cause of death

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Dozen Ds of Botulism

• dry mouth
• diplopia
• dilated pupils
• droopy eyes
• droopy face
• diminished gag reflex

• dysphagia
• dysarthria
• dysphonia
• difficulty lifting head
• descending paralysis
• diaphragmatic paralysis

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Botulism

• Investigation
• Foodborne serum analysis for toxin by bioassay
  in mice
• Analysis of stool, vomitus, and suspected food
  items may also reveal toxin
• Infantile isolation of C.botulinum spores
  toxin detection in stool
• EMG
• Treatment
• Equine serum heptavalent botulism antitoxin
• Children older than 1 year of age and adults
• Human derived botulism immune globulin (BIG-IV or
  BabyBIG)
• Infants less than 1 year of age

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Key points

• 20/30/40 rule
• Identify pts at risk for resp failure EARLY to
  avoid emergency intubation
• Dont wait for pts to complain of dyspnea before
  doing bedside PFTs