Neuromuscular weakness

Neuromuscular Junction Disorders

Myasthenia Gravis: Autoimmune disorder characterized by fluctuating muscle weakness, often worse with exertion and improved with rest; commonly affects ocular, bulbar, and proximal limb muscles.
Lambert-Eaton Myasthenic Syndrome (LEMS): Paraneoplastic syndrome often associated with small cell lung cancer; presents with proximal muscle weakness and autonomic symptoms, often improving with activity.
Botulism: Caused by Clostridium botulinum toxin; leads to descending flaccid paralysis, starting with cranial nerves and progressing to respiratory failure.

Peripheral Nerve Disorders

Guillain-Barré Syndrome (GBS): Acute inflammatory demyelinating polyneuropathy; presents with ascending weakness, areflexia, and autonomic dysfunction; often follows an infection.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Similar to GBS but with a chronic or relapsing course; presents with symmetrical weakness, sensory loss, and hyporeflexia.
Peripheral Neuropathies: Can be caused by diabetes, alcoholism, vitamin deficiencies, or toxins; presents with distal weakness, sensory loss, and often a stocking-glove distribution.
Mononeuropathies: Focal nerve injuries, such as carpal tunnel syndrome or Bell’s palsy, presenting with weakness in the distribution of the affected nerve.

Muscle Disorders (Myopathies)

Duchenne Muscular Dystrophy: X-linked recessive disorder presenting in early childhood with proximal muscle weakness, calf hypertrophy, and elevated creatine kinase (CK); progresses to respiratory failure.
Becker Muscular Dystrophy: Milder form of Duchenne, with later onset and slower progression; patients may remain ambulatory into adulthood.
Polymyositis and Dermatomyositis: Inflammatory myopathies presenting with symmetrical proximal muscle weakness, elevated CK, and characteristic skin changes (in dermatomyositis).
Metabolic Myopathies: Includes disorders like McArdle disease (glycogen storage disease) and mitochondrial myopathies; presents with exercise intolerance, muscle pain, and weakness.

Spinal Cord Disorders

Amyotrophic Lateral Sclerosis (ALS): Progressive neurodegenerative disorder affecting both upper and lower motor neurons; presents with asymmetric limb weakness, muscle atrophy, fasciculations, and hyperreflexia.
Spinal Cord Compression: Can be caused by trauma, malignancy, or abscess; presents with weakness, sensory loss, and autonomic dysfunction below the level of the lesion.
Transverse Myelitis: Inflammatory disorder causing demyelination across the spinal cord; presents with acute onset of weakness, sensory changes, and bladder/bowel dysfunction.
Syringomyelia: Fluid-filled cavity within the spinal cord, often associated with Chiari malformation; presents with segmental weakness, sensory loss (cape-like distribution), and possibly scoliosis.

Symptomatology

Onset and Duration: Acute onset suggests conditions like GBS or stroke, whereas chronic, progressive weakness may indicate a myopathy or motor neuron disease.
Pattern of Weakness: Proximal weakness is typical of myopathies, while distal weakness suggests neuropathies; symmetrical weakness suggests systemic conditions, while asymmetry may indicate a focal lesion.
Associated Symptoms: Ask about sensory loss, autonomic symptoms, and fatigue, which can help differentiate between neuromuscular junction disorders, peripheral neuropathies, and myopathies.
Triggers and Relievers: Identify factors that worsen or improve symptoms; for example, weakness that improves with rest and worsens with activity is characteristic of myasthenia gravis.
Impact on Daily Life: Assess how the weakness affects mobility, activities of daily living, and respiratory function; significant impact may indicate a need for urgent intervention.

Background

Past Medical History: Important to note any history of autoimmune diseases, infections, diabetes, or thyroid disorders.
Drug History: Review medications that may cause neuromuscular weakness, such as statins, steroids, or chemotherapy agents.
Family History: Consider family history of neuromuscular disorders, genetic syndromes, or metabolic conditions.
Social History: Assess lifestyle factors such as alcohol use, smoking, occupation, and physical activity that might contribute to or exacerbate neuromuscular weakness.
Recent Infections: Ask about recent viral or bacterial infections, particularly in the context of GBS or post-infectious myopathies.

Laboratory Tests

Full Blood Count and CRP: Useful to assess for infection, inflammation, or hematologic causes of weakness.
Creatine Kinase (CK): Elevated in myopathies such as polymyositis, dermatomyositis, and muscular dystrophies.
Electrolyte Panel: Assess for electrolyte imbalances such as hypokalemia or hyperkalemia that can cause muscle weakness.
Autoantibody Screen: Consider in suspected autoimmune conditions, such as myasthenia gravis (anti-AChR antibodies) or lupus (ANA, anti-dsDNA).
Thyroid Function Tests: Hyperthyroidism or hypothyroidism can present with muscle weakness.
Nerve Conduction Studies and Electromyography (EMG): Essential for diagnosing neuromuscular junction disorders, peripheral neuropathies, and myopathies.

Imaging and Specialist Tests

MRI of Brain and Spine: Consider if there is suspicion of a central nervous system cause, such as multiple sclerosis, stroke, or spinal cord compression.
CT Scan: May be useful in assessing for structural abnormalities or masses compressing nerves.
Muscle Biopsy: Indicated if a primary muscle disorder is suspected and to differentiate between inflammatory, dystrophic, and metabolic myopathies.
Lumbar Puncture: CSF analysis is important in the diagnosis of GBS (elevated protein with normal cell count) or other inflammatory conditions.
Genetic Testing: Consider if there is suspicion of a hereditary condition such as muscular dystrophy or channelopathies.

Neurosciences