Clinical Presentations of Neuromuscular Junction (NMJ) Disorders
Neuromuscular junction disorders typically present with fluctuating muscle weakness that worsens with repetitive use and improves with rest, with specific patterns depending on whether the pathology is presynaptic, synaptic, or postsynaptic. 1, 2
General Characteristics of NMJ Disorders
- NMJ disorders are characterized by fluctuating muscle weakness that varies throughout the day and worsens with sustained or repetitive activity 2
- These disorders can be classified based on the site of neuromuscular transmission failure as presynaptic (e.g., Lambert-Eaton myasthenic syndrome), synaptic (e.g., cholinesterase inhibitor toxicity), or postsynaptic (e.g., myasthenia gravis) 2
- The prevalence of acquired myasthenia gravis, the most common NMJ disorder, is estimated at approximately 0.5 to 12.5 per 100,000 people 1
Clinical Presentation of Myasthenia Gravis (Postsynaptic NMJ Disorder)
- Ocular symptoms are the initial presentation in approximately 50-60% of patients, including ptosis and diplopia 1
- Weakness typically increases with sustained or repetitive muscle use and improves with rest 3
- Distribution of weakness often involves:
- Symptoms typically worsen as the day progresses or with prolonged activity 3
- Reflexes are preserved, and sensory function remains intact 3
Clinical Presentation of Lambert-Eaton Myasthenic Syndrome (Presynaptic NMJ Disorder)
- Presents primarily with proximal muscle weakness, particularly in the lower limbs 1
- Characteristic finding is initial weakness that temporarily improves with repeated or sustained effort (facilitation) 3
- Autonomic symptoms are common, including dry mouth, constipation, and erectile dysfunction 1
- Approximately 60% of cases are paraneoplastic, most commonly associated with small cell lung cancer 3
- Deep tendon reflexes are typically reduced or absent but may transiently increase after exercise 3
Clinical Presentation of Botulism (Presynaptic NMJ Disorder)
- Presents with descending paralysis, beginning with cranial nerves and progressing downward 1
- Early symptoms include diplopia, ptosis, fixed dilated pupils, and dysarthria 3
- Prominent autonomic symptoms include dry mouth, ileus, urinary retention, and orthostatic hypotension 3
- Respiratory failure may develop rapidly, requiring mechanical ventilation 1
Clinical Presentation of Congenital Myasthenic Syndromes
- Onset typically in infancy or early childhood with variable severity 3
- Symptoms may include feeding difficulties, weak cry, ptosis, ophthalmoplegia, and delayed motor milestones 1
- Respiratory crises may occur during infections or stress 3
- Family history may be positive due to genetic inheritance patterns 1
Diagnostic Approach
- Repetitive nerve stimulation showing decremental response is recommended for diagnosis of postsynaptic NMJ disorders 1
- Single fiber electromyography (SFEMG) is more sensitive than repetitive nerve stimulation and should be used if clinical suspicion remains high despite normal RNS 1
- Serological testing for specific antibodies helps confirm the diagnosis:
Diagnostic Pitfalls and Mimics
- NMJ disorders may be misdiagnosed due to their variable presentation and overlap with other neurological conditions 4
- Overreliance on serological tests alone can lead to misdiagnosis, particularly in seronegative cases 4
- Conditions that may mimic NMJ disorders include:
- Cranial nerve palsies
- Thyroid eye disease
- Mitochondrial myopathies
- Motor neuron disease
- Brainstem lesions 4
Clinical Red Flags Suggesting Alternative Diagnoses
- Fixed rather than fatigable weakness 4
- Sensory symptoms or signs 3
- Bowel or bladder dysfunction (except autonomic symptoms in LEMS) 4
- Cognitive impairment 4
- Lack of response to acetylcholinesterase inhibitors 3
Understanding the typical clinical presentations of NMJ disorders is crucial for early recognition and appropriate management to prevent life-threatening complications such as respiratory failure.