Nutrient Insufficiency in Myeloneuropathy

Myeloneuropathy is characterized by simultaneous damage to the spinal cord tracts and peripheral nerves in the lower limbs. Patients commonly present with difficulty walking, lower limb weakness, ataxic gait, and sensory symptoms.

Examination may reveal myelopathic signs such as hyperreflexia, spasticity, extensor plantar responses, and occasionally bladder and bowel disturbances, indicating involvement of the posterior column as evidenced by a positive Romberg sign.

Neuropathic signs include sensory loss in a glove and stocking pattern, reduced or absent ankle jerks, and distal limb atrophy. Some patients may also experience cognitive impairment and vision loss due to optic nerve damage, with severe sensory ataxia contributing to gait difficulties.

Myeloneuropathy can result from various causes, including nutritional deficiencies of vitamin B12, folate, copper, and vitamin E, leading to conditions like subacute combined degeneration of the spinal cord.

Micronutrients and Myeloneuropathy

Nutritional deficiencies can cause myeloneuropathy manifesting as subacute combined degeneration involving the spinal cord, brain parenchyma, and peripheral and optic nerves. Progressive symptoms include paresthesias, sensory loss, gait ataxia, lower limb weakness, spasticity, hyperreflexia, and extensor plantar responses.

Vitamin B12

Vitamin B12 deficiency commonly begins with paresthesia or ataxia, and patients often exhibit diminished vibration and proprioception in the lower limbs. Additional neurological signs include motor weakness, loss of sensation, decreased deep tendon reflexes, spasticity, urinary or fecal disturbances, postural hypotension, vision loss, dementia, psychoses, and mood changes; Lhermitte's sign is also frequently observed in cases of subacute combined degeneration. The deficiency is particularly prevalent among the elderly and individuals who have undergone gastric surgery, primarily due to intrinsic factor-related malabsorption similar to pernicious anemia.

Biochemically, a lack of vitamin B12 impedes the conversion of methylmalonyl-CoA to succinyl-CoA, leading to the accumulation of neurotoxic methylmalonic acid, which damages myelin in the posterior columns of the spinal cord—lesions are predominantly found in the lower cervical and upper thoracic regions. Diagnosis involves detecting low serum B12 levels, and if these are borderline, elevated homocysteine and methylmalonic acid levels can confirm the deficiency. Nitrous oxide anesthesia can exacerbate or unveil B12 deficiency symptoms by inactivating the vitamin and impairing methionine synthetase; even a single exposure can trigger severe neurological manifestations in predisposed individuals. Administering high doses of vitamin B12 can counteract these effects, often leading to dramatic clinical improvement.

Folate

Folate deficiency can lead to a clinical picture similar to subacute combined degeneration of the spinal cord, often occurring alongside other deficiencies like vitamin B12. Causes include dietary deficiency, malabsorption syndromes, pregnancy and lactation, use of anticancer, antiepileptic, or oral contraceptive drugs, and chronic alcoholism. Myeloneuropathy associated with folate deficiency partially responds to folate supplementation.

Vitamin E

Vitamin E deficiency typically presents with a spinocerebellar syndrome but can also manifest as myeloneuropathy. Known as ataxia with vitamin E deficiency, an autosomal recessive disorder, its clinical features resemble those of Friedreich's ataxia. Patients often exhibit cerebellar ataxia, loss of deep tendon reflexes, loss of vibration sense, dysarthria, and a positive Babinski sign, with additional symptoms like head titubation, retinopathy, and dystonia being more common. Early diagnosis is crucial for successful treatment.

Copper

Copper deficiency is an important differential diagnosis in patients presenting with myeloneuropathy involving the posterolateral spinal cord. Predisposing factors include enteral feeding, gastrectomy, use of copper-chelating agents, and excessive zinc administration. Excessive zinc intake leads to copper deficiency because zinc and copper compete for absorption in the small intestine; zinc interferes with copper absorption and induces the synthesis of metallothionein, a protein that binds copper with high affinity, leading to its excessive excretion. Therefore, serum levels of copper and zinc should be closely monitored when administering oral copper replacement, especially in patients also receiving supplemental zinc.

Common nutritional, metabolic, and toxic causes of myeloneuropathy: Etiology, diagnosis, and treatment

Optimal Takeaways

• Diagnosing myeloneuropathy is challenging because deficiencies in vitamin B12, folate, copper, and vitamin E produce similar clinical pictures that mimic subacute combined degeneration of the spinal cord.
• The pattern of neurological involvement and comprehensive biochemical tests are crucial for establishing the correct diagnosis.
• Upon diagnosing myeloneuropathy, patients should undergo tests assessing blood levels of vitamin B12, folate, methylmalonic acid, homocysteine, vitamins A, D, E, K, iron, and calcium to detect additional nutritional deficiencies.
• Imaging studies of the brain and spinal cord with contrast are essential for thorough evaluation.
• Electromyography and nerve conduction studies typically show axonal sensorimotor polyneuropathy in the legs, and somatosensory evoked potentials can reveal dysfunction in central neural pathways.
• Early recognition of dietary and nutritional deficiency causes is vital; factors include malabsorption, gastrointestinal surgery, pregnancy, lactation, use of anticancer, antiepileptic, or oral contraceptive drugs, and long-term alcoholism.
• Nutrient repletion:
  
  • B12: 1 mg intramuscularly for five days followed by monthly supplementation
  • Folate: 1 mg daily
  • Vitamin E: 200-600 mg daily
  • Copper: 2-4 mg/day for 6 days for 4-12 weeks

• Methylcobalamin and adenosylcobalamin are the active preferred forms of B12
• 5-methyltetrahydrofolate is the active preferred form of folate
• Full-spectrum mixed tocopherols and tocotrienols are the preferred form of vitamin E
• Sufficient copper intake should be continued with prolonged high-dose zinc supplementation
  
  

Reference

Garg, Ravindra Kumar et al. “Approach to a case of myeloneuropathy.” Annals of Indian Academy of Neurology vol. 19,2 (2016): 183-7. doi:10.4103/0972-2327.182303 This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License