4.7 Article

Clinicopathologic features of folate-deficiency neuropathy

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NEUROLOGY
卷 84, 期 10, 页码 1026-1033

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000001343

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  1. Ministry of Education, Culture, Sports, Science and Technology
  2. Ministry of Health, Labour, and Welfare of Japan
  3. Grants-in-Aid for Scientific Research [26461292, 15K09344, 25461276] Funding Source: KAKEN

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Objective: The clinical significance and characteristics of neuropathy caused by folate deficiency remain to be established. Methods: We examined the clinicopathologic features of 18 consecutive patients with neuropathy caused by folate deficiency who presented with low serum folate levels but normal blood thiamine and serum cobalamin levels in the absence of chronic alcoholism. Results: Symptoms were relatively uniform, characterized by slowly progressive polyneuropathy with predominant involvement of the lower extremities, with a tendency to manifest as sensory rather than motor neuropathy and predominant deep rather than superficial sensory loss. The electrophysiologic features were consistent with axonal neuropathy. The histopathologic features of sural nerve biopsy specimens indicated large fiber-predominant axonal loss without segmental demyelination. Although macrocytosis was found in 7 patients, only 3 patients exhibited hemoglobin levels less than 10 g/dL. During the same study period, we found 12 patients who had low blood thiamine levels but normal serum folate and cobalamin levels without chronic alcoholism. Compared with patients who had thiamine-deficiency neuropathy, patients with a folate deficiency showed significantly slower progression (p < 0.01), a tendency tomanifest sensory neuropathy (p < 0.05), predominant deep sensory loss (p < 0.01), and preservation of biceps tendon reflexes (p < 0.05). Conclusions: Folate-deficiency neuropathy was characterized by a slowly progressive and sensory-dominant pattern, which was different from thiamine-deficiency neuropathy (i.e., beriberi neuropathy). This study demonstrates the importance of folate deficiency in the differential diagnosis of neuropathy, particularly in countries where folic acid fortification has not yet been practiced.

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