By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: In a careful prospective collection of features of chronic idiopathic axonal neuropathy, with retrospective ascertainment of vitamin B6 levels in the blood, the investigators reported there was no significant correlation between the severity of neuropathy symptoms and plasma B6 levels.
SOURCE: Stewart SL, Thomas S, Hoke E, et al. Vitamin B6 levels do not correlate with severity of neuropathy in chronic idiopathic axonal polyneuropathy. J Periph Nerv Syst 2021; Dec 21. doi: 10.1111/jns.12480. [Online ahead of print].
First reported in 1983 in the New England Journal of Medicine as a new megavitamin syndrome, large doses of pyridoxine (vitamin B6), previously known to result in photosensitivity, dermatoses, dizziness, and nausea, now were associated with gradually progressive sensory ataxia caused by sensory neuropathy or neuronopathy. Although vitamin B6 generally is considered to be safe at any dose, like other water-soluble vitamins, seven patients taking 2 g or more daily for two months or more developed the syndrome and were the subjects of the paper. Small fiber functions were less affected and weakness was not an issue. Improvement occurred after stopping B6, with “satisfactory recovery” reported in those examined after prolonged follow-up.
Chronic idiopathic axonal neuropathy (CIAP) describes a length-dependent axonal neuropathy affecting sensory and motor nerves with insidious onset and slow progression over several months, with no etiology identified. Do B6 levels correlate with the severity of CIAP or influence its progression?
CIAP patients enrolled in the Peripheral Neuropathy Research Registry (PNRR), a multicenter database and biorepository of well-characterized patients with distal, symmetrical polyneuropathies, were the subjects of this study, culled from three of the consortia sites, Johns Hopkins University School of Medicine, Icahn School of Medicine at Mount Sinai, and the University of Utah. All 216 CIAP patients satisfied inclusion criteria, including a plasma vitamin B6 value available within three years of study enrollment, no history of vitamin B6 deficiency (0 µg/L to 4.9 µg/L), and a complete PNRR dataset, comprising neurological examination, nerve conduction studies (NCS), laboratory testing for common underlying etiologies of neuropathy as recommended by the American Academy of Neurology, and a questionnaire evaluating the nature and severity of neuropathy, including pain, numbness, weakness, balance, and autonomic symptoms. Patients were divided by normal (5 µg/L to 50 µg/L) or elevated (> 50.0 µg/L) plasma vitamin B6 level. Overall neuropathy severity was assessed using the Total Neuropathy Score-reduced, which comprises pinprick and vibration sensitivity, muscle strength, absence of deep tendon reflexes, and degree of paresthesiae extension as measured by pain and numbness. Statistical analysis included T-test analysis and the Chi-square test.
Among the 261 CIAP patients, 67.8% demonstrated normal B6 plasma levels (5 µg/L to 50.0 µg/L), 15.9% were mildly elevated (50.1 µg/L to 99.9 µg/L), and 16.3% were above 100 µg/L. Those taking a vitamin B6 supplement, B-complex, or multivitamin were more likely to have elevated plasma B6 levels compared to those not taking supplements, but B6 level was not related to severity of neuropathy, patient reported pain or numbness intensity, NCS results, or neurological examination findings, including toe strength, vibration sensitivity, or deep tendon reflexes.
Moderately elevated plasma B6 levels are not associated with more severe CIAP, and supplementation of B6 does not negatively affect CIAP. Given that few patients in this study had B6 levels above 300 µg/L, screening for B6 toxicity remains discretionary.
COMMENTARY
The search for an underlying etiology of CIAP is ongoing and as yet incomplete. Prior reports of an association between statin use and the development of neuropathy have not been borne out in a recent MEDLINE and EMBASE database review, from inception to Oct. 31, 2020, which included all cohort and case-control studies, covered 4,968 articles, and involved two meta-analyses.1 Regarding CIAP and a possible role of human leukocyte antigen genetic susceptibility in its development, among 57 CIAP patients, the DQA1*05 allele was more frequently found compared to healthy controls, suggesting as an association between this allele and CIAP. It is hoped larger studies will shed further light on this intriguing finding.2
REFERENCES
- Wannarong T, Chaikijurajai T, Preston DC, et al. Statins and the risk of polyneuropathy: A systematic review and two meta-analyses. Muscle Nerve 2022;65:120-125.
- Panagiotis Z, Sarrigiannis PG, Artemiadis A, et al. Chronic idiopathic axonal polyneuropathy: Electrophysiological progression and human leukocyte antigen associations. Muscle Nerve 2021;63:567-571.
