title: Clinicopathologic features of folate-deficiency neuropathy.
abstract: 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 to manifest 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.
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan. koike-haruki@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
authors: Haruki
authors: H
authors: Koike
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Mie
authors: M
authors: Takahashi
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Ken
authors: K
authors: Ohyama
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Rina
authors: R
authors: Hashimoto
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Yuichi
authors: Y
authors: Kawagashira
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Masahiro
authors: M
authors: Iijima
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Masahisa
authors: M
authors: Katsuno
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Hiroshi
authors: H
authors: Doi
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan.
authors: Fumiaki
authors: F
authors: Tanaka
authors: From the Department of Neurology (H.K., M.T., K.O., R.H., Y.K., M.I., M.K., G.S.), Nagoya University Graduate School of Medicine; and Department of Neurology and Stroke Medicine (H.D., F.T.), Yokohama City University Graduate School of Medicine, Japan. koike-haruki@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
authors: Gen
authors: G
authors: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000150:complications; D001602:Beriberi / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000097:blood / Q000150:complications* / Q000178:diet therapy / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013497:Sural Nerve / Q000473:pathology; D016896:Treatment Outcome; D014806:Vitamin B 12 Deficiency / Q000503:physiopathology; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid