10.1.1 Definition

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  Acute immune-mediated polyradiculoneuropathy characterized by flaccid ascending weakness with areflexia, and, when severe, neuromuscular respiratory failure. ^{1 , 2 , 3 , 4}

  
  
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  Monophasic course with symptom onset to nadir of weakness <4 weeks. ³

  
  
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  Most often caused by demyelination and occasionally caused by axonal type. ⁴

10.1.2 Epidemiology

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  Worldwide incidence of 1 to 2 per 100,000 per year. ³

  
  
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  Median age is 53 years old with a ratio of men to women of 1.78. ^{2 , 3}

  
  
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  Mortality ranges between 3 and 13% with higher mortality in patients who require mechanical ventilation. ⁷

  
  
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  Respiratory failure, pneumonia, autonomic dysautonomia, and cardiac arrest are the most common causes of death in these patients. ⁷

10.1.3 Differential Diagnosis

Bilateral strokes, posterior fossa structural lesion, transverse myelitis, compressive myelopathy, anterior spinal artery syndrome, poliomyelitis, acute infectious myelitis (West Nile virus, coxsackie, echovirus), Lyme disease, botulism, myasthenia gravis (MG), neuromuscular blocking agents, acute viral myositis, acute inflammatory or metabolic myopathies, periodic paralysis, and psychogenic symptoms

10.1.4 Common Clinical Presentation

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  Two-thirds of cases are preceded by respiratory infection or gastroenteritis days to weeks before (most commonly Campylobacter jejuni, cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], and Mycoplasma pneumoniae). ^{3 , 4}

  
  
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  Initial symptoms: Numbness, paresthesias, weakness, dysautonomia, and pain in limbs. ^{1 , 3}

  
  
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  Cardinal features: Progressive, bilateral, and symmetric ascending weakness of the limbs with hypo/areflexia which progresses over days to weeks. ^{3 , 4}

  
  
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  Dysautonomia occurs in 70% of patients. ⁴ Dysautonomia is characterized by wide fluctuations in blood pressure and respiratory rate, tachyarrhythmias, bradyarrhythmias, urine retention, diaphoresis, and gastric slowing causing ileus.

10.1.5 Diagnosis

See Table 10‑1.

10.1.6 GBS Variants

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  GBS/AIDP: Areflexia, mild sensory changes, distal paresthesias, loss of deep tendon reflexes (DTR), ascending paralysis, respiratory failure, and autonomic dysautonomia

  
  
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  Acute motor axonal neuropathy (AMAN): Acute, flaccid ascending paralysis associated with GM1 and GD1a ganglioside antibodies

  
  
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  Acute motor and sensory axonal neuropathy (AMSAN): Loss of DTR, distal weakness, and sensory symptoms (GM1 and GD1a antibodies)

  
  
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  Miller-Fisher syndrome (MFS): Ophthalmoplegia, ataxia, areflexia (GQ1b and GT1a antibodies)

  
  
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  Bickerstaff encephalitis: Encephalopathy, ophthalmoplegia, and ataxia with areflexia to hyperreflexia (GQ1b and GT1a antibodies)

10.1.7 Ancillary Testing

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  Autoimmune and infectious workup (can be presenting sign of human immunodeficiency virus [HIV])

  
  
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  Serum ganglioside antibodies (GM1, GD1a, GQ1b, and GT1a) when considering a GBS variant

  
  
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  Lumbar puncture can rule out infectious diseases or malignancy. ^{3 , 4}

  
  
  
  
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    Albuminocytologic dissociation (elevated cerebrospinal fluid [CSF] protein with normal CSF white blood cell [WBC]) seen in 50% of patients’ CSF in the first week and proportion increases with time. ^{3 , 4}

  
  
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  Nerve-conduction studies (NCS) help confirm the presence, pattern, and severity of neuropathy.

  
  
  
  
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    Prolonged F-wave latencies, prolonged distal motor latencies, temporal dispersion, conduction block, and slow motor nerve conduction velocities (typically in demyelinating range). ¹

    
    
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    Note that NCS are usually not performed immediately and can be delayed by up to 2 weeks.

10.1.8 Complications of GBS

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  Cardiac: Labile blood pressure (70%), hypertension, hypotension, arrhythmias, tachycardia, bradycardia (4%), atrioventricular (AV) blocks, and asystole

  
  
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  Pulmonary: Respiratory failure, pneumonia, aspiration, atelectasis, and mucus plugging

  
  
  
  
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    Ventilator support is required by 20 to 30% of patients. ⁵

  
  
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  Gastrointestinal: Gastroparesis and adynamic ileus

  
  
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  Genitourinary: Bladder dysfunction, retention, and incontinence

  
  
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  Endocrine: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) (monitor sodium and fluid status)

  
  
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  Hematologic: Venous thromboembolism and pulmonary embolism

  
  
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  Neuropathic pain (40–50%): Use gabapentin or carbamazepine in acute phase.

10.1.9 Management

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  Monitor respiratory function closely. Intubation may be required if vital capacity (VC) is <20 mL/kg and maximum negative inspiratory force (NIF) is <30 cm H₂O (or a reduction of 50% from baseline VC or NIF). ¹

  
  
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  Treatment with intravenous immunoglobulin (IVIG) or plasma exchange hastens recovery from GBS if initiated within 4 weeks of the onset of symptoms. Combining these two treatments is not beneficial. ^{1 , 6} See Table 10‑2.

  
  
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  Corticosteroid treatment is not effective and therefore not recommended. ^{1 , 6}

10.1.10 Prognosis

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  At 1 year

  
  
  
  
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    84% of patients will be able to walk.

    
    
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    5 to 10% of patients have incomplete recovery.

    
    
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    4 to 5% of patients with GBS die despite intensive care. ^{1 , 7}

  
  
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  Relapses can occur in approximately 10% of patients.

10.2.1 Definition

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  Autoimmune disorder affecting postsynaptic neuromuscular transmission at the neuromuscular junction (NMJ), producing characteristic variable and fatigable weakness in skeletal muscles. ^{8 , 9 , 10 , 11}

  
  
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  Myasthenic crisis is a complication of MG with worsening muscle weakness, resulting in respiratory failure that often requires intubation and mechanical ventilation. ^{11 , 12 , 13}

10.2.2 Epidemiology

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  Prevalence is about 20 per 100,000. ¹⁰

  
  
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  Bimodal distribution with age of onset: Early peak in the 2nd and 3rd decades (female predominance) and late peak in the 6th to 8th decades (male predominance). ¹⁴

  
  
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  The median time from onset of MG to first myasthenic crisis is 8 to 12 months. However, myasthenic crisis may be the initial presentation of MG in 20% of patients. ¹¹

10.2.3 Differential Diagnosis

Lambert-Eaton myasthenic syndrome, GBS, organophosphate toxicity, botulism, congenital myasthenia syndromes, thyroid ophthalmopathy, mitochondrial disorders, myotonic dystrophy, skull-based tumors, and motor neuron disease.

10.2.4 Clinical Presentation of Generalized Myasthenia Gravis

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  Presents with several days/weeks of worsening ptosis, diplopia, bulbar symptoms, extremity weakness, and/or shortness of breath. ⁹

  
  
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  Physical examination findings: Ptosis, inability to sustain upgaze, normal pupillary reflexes, bulbar weakness, flaccid dysarthria, neck flexor/extensor weakness, proximal > distal limb weakness, tachypnea, intact sensation, and decreased reflexes. ¹⁰

10.2.5 Diagnosis

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  Diagnosis is based on history and physical examination and supported by electrophysiologic and serologic studies.

  
  
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  Electrophysiologic studies

  
  
  
  
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    Repetitive nerve stimulation: Low rates of repetitive stimulation (2–5 Hz) deplete acetylcholine and cause >10% decrement in compound muscle action potential (CMAP) amplitude (80% sensitive for generalized MG). ^{9 , 10}

    
    
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    Single fiber electromyography (EMG): Increased jitter or variation in contraction time between pairs of muscle fibers (95% sensitive, nonspecific). ^{9 , 10}

  
  
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  Serologic antibody tests are positive in >90% of MG patients.

  
  
  
  
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    Acetylcholine receptor (AChR) antibodies

    
    
    
    
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      Present in 85% of patients with generalized MG ^{9 , 10}

      
      
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      Highly specific for MG (>99%)

      
      
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      Correlate with thymic hyperplasia and thymoma

    
    
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    Muscle-specific kinase (MuSK) antibodies: Found in 40% of patients with generalized MG who are negative for AChR antibodies. ⁹

    
    
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    Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies: Found in 18% of patients with generalized MG who are negative for AChR and MuSK. ⁹

  
  
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  Ancillary tests: CT of chest with contrast to evaluate for thymoma

10.2.6 Management of Myasthenic Crisis

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  Supportive care: Aspiration precautions, temporary nil per os (NPO) with nasogastric tube feedings, frequent monitoring with NIF and VC, and ventilatory support. ABGs are insensitive.

  
  
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  Treatment typically consists of high-dose steroids with either IVIG or plasma exchange. See Table 10‑3.

  
  
  
  
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    Plasma exchange is more efficacious than IVIG but has higher complication rate. ¹¹

  
  
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  Thymic tumors are found in 32% of patients with myasthenic crises, which should be treated with thymectomy when myasthenic crisis is resolved. ¹¹

10.2.7 Prognosis

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  Overall, the outcome for patients with myasthenic crisis is good if therapeutic measures are instituted quickly. Extubation failure rate is around 27%. Mortality rate is approximately 5%. ^{12 , 13}

  
  
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  One-third of patients with myasthenic crisis will experience a recurrent episode.

10.3.1 Definition

Rare but potentially life-threatening neuroparalytic syndrome caused by neurotoxin of the bacterium Clostridium botulinum. ^{15 , 16}

10.3.2 Epidemiology

Approximately 110 cases of botulism are reported each year in USA. Of these cases, around 72% are infant botulism, 25% are foodborne botulism (typically from improperly canned foods), and 3% are wound botulism. ¹⁵

10.3.3 Pathophysiology

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  C. botulinum is a gram-positive, rod-shaped, spore-forming, anaerobic bacterium. ¹⁵

  
  
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  Spores of C. botulism produce a very potent toxin which blocks neurotransmitter release at peripheral cholinergic nerve terminals. ¹⁷

  
  
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  Toxin binds irreversibly to receptors on presynaptic membrane of NMJ. It is internalized by endocytosis, and then cleaves SNARE proteins preventing transmitter exocytosis. This blocks the release of acetylcholine from the presynaptic motor nerve terminal resulting in skeletal muscle paralysis and autonomic dysfunction. ¹⁸

10.3.4 Differential Diagnosis

Stroke, GBS, MG, Lambert-Eaton myasthenic syndrome, diphtheric polyneuropathy, poliomyelitis, tick paralysis, hypermagnesemia, and curare poisoning.

10.3.5 Clinical Presentation

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  Neuromuscular symptoms begin 2 to 36 hours after exposure. Weakness progresses for several days then plateaus. Fatal respiratory paralysis may occur rapidly. ^{18 , 19 , 20}

  
  
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  Classic triad: Afebrile, symmetrical descending flaccid paralysis, and intact mental status.

  
  
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  Physical examination findings: Fixed dilated pupils with impaired pupillary reflex, ptosis, ophthalmoplegia, facial weakness, dysarthria, dysphagia, dry mouth, urinary retention, postural hypotension, and intact sensation. ¹⁵