Disorders of the Neuromuscular Junction

Abstract

The chapter begins with a general discussion of synapses and their neurotransmitters. In humans, all nerve to nerve, nerve to muscle, and peripheral sensory receptor to nerve communication occurs via synapses. An electrical signal traveling along a nerve axon is converted at a specialized nerve ending called a synapse. There are at least 30 different neurotransmitters, with the greatest number occurring in the CNS. Neurotransmitters are classified into simple chemicals (acetylcholine, norepinephrine, dopamine), amino acids (gamma amino butyric acid [GABA], glycine, glutamine), or peptides (substance P, endorphins). Next, the chapter discusses pathological diseases of the synapse called synaptopathies, which may occur from chemical or biologic toxins, antibodies directed against synaptic receptor molecules, or genetic mutations in the synaptic receptor or membrane channel. The major synaptopathies, myasthenia gravis, Lambert–Eaton myasthenic syndrome, and botulism, are reviewed with attention to their pathophysiology, major clinical features, major laboratory findings, and principles of management and prognosis.

A 37-year-old woman presents to her primary care doctor with several months of feeling weak and seeing double. She reports that she first noticed the weakness when the family was moving into a new house. Her husband told her that she looked tired as her eyelids were droopy. Shortly after that, she noticed some double vision late in the day. She noted that packing the kitchen was particularly difficult when moving things from higher shelves down for packing. She had to take several rests in order to complete the packing. She thought this was normal and just related to the stress of moving. But the weakness and fatigue have not gotten better and became worried that something was really wrong. On exam, the patient has ptosis and fatigable weakness on holding her arms outstretched. A glove with ice is placed on her eyes with resolution of the ptosis. A clinical diagnosis of myasthenia gravis was made and the appropriate confirmatory tests were ordered.

Video Legend

This video shows a 67 year-old man with Myasthenia Gravis.

Segment 1: Symptom Description

• Patient describes his ocular myasthenia symptoms: diplopia, ptosis and fatigue.

Segment 2: Cranial Nerve Exam

• Diplopia at both extremes of gaze

• Binocular diplopia—the diplopia resolves with covering one eye

• Patient does not have full excursion with lateral gaze

• Ptosis

• Divergent gaze due to NMJ weakness

• Normal jaw and neck strength