Transcript Neuromuscular Emergencies

Neuromuscular Emergencies
Hanni Bouma
R3 Neurology
Outline
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Approach to neuromuscular respiratory
failure
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Signs & Symptoms
Investigations
Knowing when (to ask someone else) to
intubate
Overview of:
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Myasthenic crisis
GBS
Botulism
True or false? Regarding GBS…
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~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.
Case 1
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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.
Case 1
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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
Case 2
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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?
Case 3
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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 trach’ed.
Now, 2 weeks later, “doing better” as per
ICU. They want to start tapering his
prednisone. What do you advise them to
do?
Case 3
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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.
Part 1:
Neuromuscular Respiratory Failure
Respiratory Failure Basics
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Type I: Hypoxia without hypercapnia
 Usually associated with ↑ WOB
 V/Q mismatch most common
 Vascular
disease/shunts (PE, Pulm.
HTN, R->L 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)
Neuromuscular Causes
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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
History
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Time course?
 progressive weakness over hours to days  GBS
 fluctuating weakness (on an hourly basis) present for
weeks/months  MG
Distribution of weakness?
 Proximal > distal (MG & GBS)
 Ascending in GBS
Sensory Sx.?
 Distal paresthesias common in GBS
 No sensory inv’t in MG
History
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+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
Exam
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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?)
Exam
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Sensory:
 Normal in MG
 Distal sensory loss in GBS, esp vib/prop
 Sensory level at C-spine level w/ quadriparesis = Cspine lesion
Coordination:
 Ataxia in MF variant of GBS
Reflexes:
 Areflexia in GBS; preserved in MG
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
Symptoms
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If subacute (ie. GBS): dyspnoea and orthopnoea
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If gradual onset, inadequate respiration usually
occurs first during sleep
Symptoms of nocturnal hypoventilation:
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Easy to overlook
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
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suggests weakness of the diaphragm
Warning signs
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Rapid, shallow breathing
Stridor
Bulbar weakness
 weak cough, nasal voice, pooling of saliva
Orthopnea
Staccato speech
Abdominal paradox
 http://www.youtube.com/watch?v=RFGzdNFu
XIM
Weakness of neck & trapezius muscles
Single-breath count
Mehta, S. “Neuromuscular disease causing acute respiratory failure.” Respiratory Care, 2006. 51 (9): 1016-1023.
Investigations
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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 < 20 ml/kg (or 1 L) means
intubation
 Max inspiratory pressure. Index of ability to
avoid atelectasis. Normal = > 80 cm H2O
(male), >70 cm H2O (female). MIP >-30
means intubation
 Max expiratory pressure. Index of ability to
cough/clear secretions. Mean MEP = 140 cm
H2O (male), 95 cm H20 (female). MEP <40
means intubation
Investigations
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ABG:
 Hypercarbia (PCO2 > 45 mmHg)
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PCO2 often normal or low until late in NM
resp failure
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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 < 75 mmHg) = usually atelectasis
or pneumonia in acute setting
Basic labs (CBC, SMA-10, LFTs, CK)
CXR
Predictors of need for MV
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20/30/40 rule
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or reduction in VC, MIP, MEP by >30%
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PO2 <70 mmHg on RA or PCO2 >50 mmHg
w/ acidosis
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Dysarthria, dysphagia, impaired gag reflex
Intubation: things to think
about
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Code status?
Call ICU if signs of imminent resp
failure
Identify early to avoid emergency
intubation…elective intubation always preferred
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Minimizes atelectasis/pneumonia
Minimizes complications of intubation specific to
NMDs
Avoid depolarizing NM blockers
NPPV?
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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
General care
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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
Part 2:
MG
GBS
Botulism
MG
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Ab-mediated attack on nicotinic Ach rec 
defective transmission across NMJ
Bimodal: F 20-30 yo; M 50-60 yo
2 autoimmune forms
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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
Presentation
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Motor:
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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:
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Malignant thymoma in 10-15% (more severe disease)
Thymic hyperplasia in 50-70%
Investigations
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Ach receptor Abs
Anti-MuSK Abs
Edrophonium (Tensilon) test: obsolete
EMG:
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Repetitive nerve stimulation: >10%
decrement in amplitude betw 1st & 5th CMAP
Single-fiber: “jitter”
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Sens >95% for MG but not specific
Management: general
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Symptomatic therapy (mild-moderate
weakness):
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Short-term disease suppression:
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Cholinesterase inhibitors (Mestinon)
To hasten clinical improvement in hospitalized pts w/
crisis or impending crisis; pre-operatively; chronic
refractory disease
PLEX or IVIG
Long-term immunosuppression:
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When weakness is inadequately controlled by
Mestinon
Prednisone
Azathioprine (if steroid failure or excessive SE)
Cyclosporine, Mycophenolate mofetil…
Myasthenic Crisis
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Defined by resp failure requiring
ventilatory assistance
Occurs in 20-30%; mortality 5%
Common precipitants:
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Infection in 40% (esp respiratory)
Medications
Surgery
Pregnancy
Aspiration
Drugs that exacerbate MG
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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
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Antipsychotics, lithium
Thyroid hormones
Magnesium toxicity
Iodinated contrast agents
Muscle relaxants
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Baclofen
Long-acting benzos
**Too much
anticholinesterase
Myasthenic crisis: management
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General
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Determine if resp failure is imminent!!
Stop any meds that may be contributing
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Mestinon usually stopped as well
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May contribute to increased airway secretions in
intubated patients
Treat any infection
Myasthenic Crisis: management
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Specific
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PLEX or IVIG:
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start one or the other, quickly
Comparable efficacy
Evidence somewhat limited…TBD later
 Earlier response seen with PLEX, but more adverse
events
 Preference somewhat individualized…
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Myasthenic crisis: management
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PLEX
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Removal of anti AChR and antiMuSK Abs
1 session/day x 5
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Rapid onset of action (3-10 days)
Need central line with associated
complications
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No superiority of PLEX qd x 5 vs qod x 5
PTX, hemorrhage, line sepsis
Caution in pts with sepsis, hypotension; may
lead to increased bleeding and cardiac
arrhythmias
Myasthenic crisis: management
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IVIG
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0.4g/kg/day x 5 days
Easily administered and widely available
Long duration of action
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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
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Therapeutic effect of PLEX & IVIG is shortlived…lasts 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 ass’d with transient worsening of
weakness, serious in up to 50%
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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
GBS
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Most common cause of acute or subacute gen’d
paralysis
Monophasic AIDP: autoimmune attack against
surface antigens on peripheral nerves
Develops 5 days to 3 weeks after resp/GI
infection in 60%
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Campylobacter jejuni (26%)
Viral URTI, influenza
EBV, CMV, VZV, HIV, hep A & B, coxsackie
Other precipitants: immunization, pregnancy,
surgery, Hodgkin’s disease
Presentation
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Sensory:
 distal paresthesias/numbness (earliest Sx.)
 Reduced vibration/proprioception
Motor:
 Symmetric; evolves over days to 1-2 wks
 Ascending: LE before UE; proximal> distal
Reflexes: reduced, then absent
Autonomic instability
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Other: low backache very common, myalgias
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Investigations
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NCS/EMG:
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Reduced conduction velocities
Loss of F waves
Conduction block in motor nerves
Reduced motor amplitudes: 2° axonal damage 
worse Px.
CSF:
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High protein (may be normal in first 2 days)
No cells or few lymphs
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10% have 10-50 lymphs
Management
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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 that…also more adverse effects
 Steroids no proven benefit
Predictors of need for MV in GBS
 Time
from onset to admission < 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 2003;31(1):278–283.
Course
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Progression over 1-4 weeks
Recovery: few wks to months
Mortality 3-5%
Poor prognosis:
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Resp failure requiring intubation
Advanced age
Very low distal motor amplitudes (axonal
damage)
Rapidly progressive weakness over 1 week
Botulism
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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
“Dozen Ds” of Botulism
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dry mouth
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diplopia
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dilated pupils
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droopy eyes
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droopy face
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diminished gag reflex
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dysphagia
dysarthria
dysphonia
difficulty lifting head
descending paralysis
diaphragmatic
paralysis
Botulism
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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
Key points
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20/30/40 rule
Identify pts at risk for resp failure EARLY
to avoid emergency intubation
Don’t wait for pts to complain of dyspnea
before doing bedside PFTs