Can a vitamin B12 (B12) deficiency cause pure motor neuropathy?

Vitamin B12 Deficiency and Pure Motor Neuropathy

Vitamin B12 deficiency primarily causes mixed sensorimotor neuropathy with prominent sensory symptoms rather than pure motor neuropathy, although motor symptoms can occur as part of the neurological manifestations. 1

Neurological Manifestations of B12 Deficiency

• B12 deficiency is associated with extensive demyelination in the central nervous system (CNS), most prominently in the spinal cord, and focal demyelination in the white matter of the brain 1
• Peripheral nervous system (PNS) involvement includes demyelination and significant damage to nerve fibers, with axonal degeneration most notable in distal afferent fibers of dorsal root ganglion neurons 1
• The clinical presentation typically includes a combination of sensory and motor symptoms, with sensory manifestations usually predominating in the early stages 1, 2

Clinical Presentation of B12 Deficiency Neuropathy

• Common neurological symptoms include paraesthesia, numbness, muscle weakness, abnormal reflexes, tendon jerks, spasticity, gait ataxia, myelopathies, and myelo-neuropathies 1
• Early symptoms are primarily connected with the loss of sensory rather than motor-unit function, specifically a decline in proprioceptive, vibratory, tactile, and nociceptive sensation 1
• B12 deficiency has a significant negative impact on nerve conduction velocity, implying a direct detrimental effect on peripheral motor function 1
• In severe cases, motor symptoms can become more prominent as the deficiency progresses 2

Pathophysiology and Evidence

• Sural nerve biopsy studies have shown the coexistence of demyelination and axonal degeneration in B12 deficiency neuropathy 3
• Nerve conduction studies in B12 deficiency typically show an axonal type sensorimotor polyneuropathy 4
• The mechanism by which demyelination occurs in B12 deficiency is not entirely clear 1
• Recovery sequence after B12 supplementation typically involves muscle power of the proximal muscles first, followed by hands, plantar flexion, and dorsiflexion of the feet, and finally sensory conduction 4

Diagnostic Considerations

• Vitamin B12 deficiency should be considered in all patients with neurologic disorders, even in those who do not have anemia 2
• Testing should include serum B12 levels, and if borderline, metabolites such as methylmalonic acid and homocysteine should be measured 1
• In patients with polyneuropathy, between 2.2-8% had evidence of B12 deficiency as indicated by elevations of these metabolites 1
• In some cases, B12 levels may be in the low-normal range (200-500 pg/dL) but metabolites are elevated, indicating functional B12 deficiency 1

Treatment Implications

• Early treatment with vitamin B12 supplementation can lead to resolution of most neurologic deficits 2
• Delayed therapy usually halts the progression of the disease, but permanent sequelae may occur 2
• Improvement can be seen as early as 1 month after initiating B12 therapy 5, 6
• Vitamin B12 deficiency that is allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord 7

Important Clinical Pitfalls

• Pure motor neuropathy without sensory involvement would be an atypical presentation of B12 deficiency and should prompt consideration of other diagnoses 1, 5
• B12 deficiency neuropathy may be underdiagnosed due to poor sensitivity of standard B12 level testing methods 5
• Folic acid supplementation may mask the hematologic manifestations of B12 deficiency while allowing neurologic damage to progress 7
• Other causes of neuropathy should be considered, including toxins, neurotoxic medications, hypothyroidism, renal disease, malignancies, infections, chronic inflammatory demyelinating neuropathy, inherited neuropathies, and vasculitis 1

In conclusion, while B12 deficiency can affect motor nerve function and cause muscle weakness, it typically presents as a mixed sensorimotor neuropathy with prominent sensory symptoms rather than a pure motor neuropathy. Any patient with neuropathic symptoms should be evaluated for B12 deficiency due to its potential reversibility with early treatment.