Neuromuscular Disordersan inpatient perspective

Joshua Alpers, MD

Objectives

• Identify common clinical presentations of Guillain-Barré syndrome and myasthenia gravis

• Develop an appropriate treatment strategy for neuromuscular emergencies

• Determine appropriate monitoring parameters for respiratory dysfunction of neuromuscular origin

• Describe common chronic neuromuscular conditions

Case presentationHistory

• 56-year-old male

• Three-week history of progressive limb weakness and dysphagia progressing to the point of being unable to safely swallow.

• He feels that his symptoms are worse as the day progresses.

Subacute progressiveNeuromuscular disorders• i.e. “Neuromuscular Emergencies”

• Myasthenia Gravis

• Guillain-Barré syndrome (GBS)• Acute inflammatory demyelinating

polyradiculoneuropathy (AIDP)

Myasthenia Gravis

• Chronic autoimmune disorder affecting the post-synaptic neuromuscular junction

• Fluctuating and fatigable weakness

• Typically ocular onset

• Acetylcholine receptor antibody positivity is not required and does not correlate with disease severity

• Evaluate for thymic pathology

• Very treatable

AIDP

• Monophasic autoimmune disorder affecting the peripheral nerves

• Preceding immunologic trigger

• Subacute progression of neurological deficits localizable to the peripheral nerves

• Typical pattern is ascending sensory loss and weakness

• CSF cytoalbuminologic dissociation occurs within several days of symptom onset

Case Presentation Neurological Examination

• Cranial nerves• Mild left ptosis• Normal pupillary reactivity• Diplopia with right lateral gaze• Mild weakness with eye closure• Severe weakness with cheek puff and tongue protrusion

• Strength examination• Moderate neck flexor weakness (MRC 4/5)• Mild to moderate weakness in the limb musculature

• Deltoids, triceps, finger extensors• Hip flexors, ankle dorsiflexors

• Normal sensory examination• Normal deep tendon reflexes (2 to 2+)

Evaluation

• MRI Brain• Mestinon Trial (Tensilon test)• Laboratory evaluation:

• CK• CBC• Quantitative immunoglobulins• CMP• TSH• (Acetylcholine receptor antibodies)

• Respiratory evaluation• FVC, NIF

• Consider lumbar puncture for CSF analysis

Treatment of Neuromuscular Emergencies• Plasmapheresis

• IVIg

• Corticosteroids• DO NOT USE

• In myasthenic exacerbation / crisis, useful as a bridging therapy AFTER onset of efficacy of rescue therapy

• Mestinon• High doses cause weakness (cholinergic crisis)

• Cholinergic side effects = sialorrhea

Supportive Care

• Monitoring respiratory function• Assess measures of respiratory force (FVC, NIF)• Ensure good seal during assessment• Consider endotracheal intubation when FVC reaches 15

mL/kg.• Hypercapnea / oxygen desaturation = imminent respiratory

failure

• Enteral feeding• NPO Speech Therapy consultation• May need NGT placement• Very limited role for PEG placement

• Cardiac monitoring• Autonomic dysfunction is common in AIDP

Myasthenia Gravis variants

• Patterns of myasthenia:• Ocular• Generalized – bulbar• Generalized – limb

• MuSK• Female (80%), typically 30-50 years old• Neck flexor weakness / bulbar impairment• Crisis is more common

• Exacerbation or Crisis?

AIDP variants

• Miller-Fisher syndrome• Triad of ataxic, areflexia, ophthalmoparesis

• GQ1b antibodies

• Pharyngeal-cervical-brachial• GT1a antibodies

• Acute motor axonal neuropathy (AMAN)• GM1, GD1a antibodies

• Other variants

Chronic Neuromuscular DisordersSecondary disorders

• Most peripheral neuropathies• Diabetes mellitus• B12 deficiency• Hypo / hyperthyroidism• Renal failure• Monoclonal gammopathies• Alcoholism• Toxic neuropathies• Connective tissue disease

• Structural radiculopathies

• Entrapment neuropathies

Treat the underlying disorder

Chronic Neuromuscular DisordersPrimary disorders

• Treatable disorders = autoimmune• Neuropathies

• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

• Multifocal motor neuropathy (MMN)

• Myopathies• Dermatomyositis

• Polymyositis

• Neuromuscular junction disorders• Myasthenia gravis

Chronic Neuromuscular DisordersPrimary disorders

• Untreatable disorders (i.e. supportive measures only)• Charcot-Marie-Tooth disorder

• Inherited polyneuropathy• Rarely life-threatening

• Amyotrophic Lateral Sclerosis (ALS)• Upper + lower motor neuron dysfunction

• Muscular dystrophy• Duchenne’s / Becker’s • Limb-Girdle• Myotonic dystrophy• Cardiac involvement / arrhythmias

• Inclusion body myositis

Summary

1. Does the presentation suggest a neuromuscular disorder?

2. What is the time course (chronic vs. subacute)?• Subacute progressive = probable role for IVIg /

plasmapheresis

3. Supportive measures• Respiratory

• Swallowing

• Cardiac

Sources

• Mahadeva B, Phillips LH, Juel VC. Autoimmune disorders of neuromuscular transmission. Semin Neurol 2008 Apr;28(2):212-27.

• Juel VC. Myasthenia gravis: Management of myasthenic crisis and perioperative care. Semin Neurol 2004 Mar;24(1):75-81.

• Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med 2012;366:2294-304.

• Burns TM. Guillain-Barré syndrome. Semin Neurol 2008 Apr;28(2):152-67.

• Merrigioli MN, Sanders DB. Myasthenia gravis: diagnosis. Semin Neurol2004 Mar;24(1):31-9.