Causes of Motor Neuropathy
Motor neuropathy results from disease processes affecting the motor axon, its myelin sheath, or the spinal motor neuron itself, with causes broadly categorized into acute versus chronic, and immune-mediated versus hereditary, infectious, toxic, or metabolic etiologies. 1, 2
Acute Motor Neuropathies
The primary acute presentations include:
- Guillain-Barré syndrome represents the most common acute motor neuropathy, presenting in both classical demyelinating and axonal forms that can be distinguished electrophysiologically 1
- Poliomyelitis causes acute motor neuron involvement with characteristic lower motor neuron syndrome 1
- Porphyrias can manifest as acute motor neuropathy during metabolic crises 1
Chronic Motor Neuropathies
Immune-Mediated (Treatment-Responsive)
These are critical to identify due to available effective therapies:
Multifocal motor neuropathy (MMN) presents with slowly progressive, asymmetric distal limb weakness without sensory loss, characterized electrophysiologically by conduction block in motor nerves with preserved sensory responses 3, 4. IgM anti-GM1 antibodies are frequently present, and intravenous immunoglobulin is efficacious in most patients 3, 4
Motor-predominant chronic inflammatory demyelinating polyneuropathy (CIDP) represents another treatable immune-mediated cause 2
Motor Neuron Diseases
- Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, though differentiation from treatable neuropathies is essential 1, 2
- Kennedy's disease (X-linked bulbospinal muscular atrophy) affects adult males with characteristic features 1, 2
- Late-onset spinal muscular atrophy and other lower motor neuron diseases may be inherited or acquired 1, 2
- Focal lower motor neuron syndrome particularly affects young adults and can mimic ALS 2
Hereditary Motor Neuropathies
- Distal hereditary motor neuropathies represent a group of genetic conditions affecting motor neurons 2
- Charcot-Marie-Tooth type 1A should be ruled out in cases of severe motor neurotoxicity, particularly with vincristine exposure, as these patients present with predominant motor involvement and distinct deformities (hollow foot, stork legs) 5
Toxic/Drug-Induced Motor Neuropathy
Chemotherapeutic agents can cause motor involvement:
Vincristine causes motor neuropathy in approximately 10% of patients, ranging from grade 1-3 distal weakness to rare life-threatening grade 4 motor neurotoxicity 5. Pre-existing axonal Charcot-Marie-Tooth disease significantly increases vulnerability 5
Bortezomib predominantly causes sensory neuropathy but motor impairment occurs in ~10% of cases with mild to severe distal weakness in lower limbs 5
Other neurotoxic chemotherapeutic agents (platinum compounds, taxanes, thalidomide) primarily affect sensory fibers but can have motor components 5
Metabolic Causes
- Diabetic neuropathy typically presents as distal symmetric polyneuropathy affecting both sensory and motor fibers, though motor involvement is less prominent 5, 6. Diabetic central neuropathy can damage motor neurons of the spinal cord 5
Infectious and Paraneoplastic
- Infectious neuropathies including those associated with HIV and other pathogens can cause motor involvement 5, 2
- Paraneoplastic motor neuropathies occur in cancer patients independent of chemotherapy effects 2
- Radiation-induced neuropathies represent another acquired cause 2
Critical Diagnostic Pitfall
The distinction between treatable immune-mediated motor neuropathies (MMN, motor CIDP) and progressive motor neuron diseases (ALS) is paramount, as prognosis and treatment differ dramatically 2, 3. Electrophysiological studies demonstrating conduction block in motor nerves without sensory abnormalities strongly suggests MMN rather than ALS 3, 4.