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Phenytoin: neuroprotection or neurotoxicity?
Jan M Keppel Hesselink1, David J Kopsky2
1Institute for Neuropathic Pain, Spoorlaan 2a, 3735 MV, Bosch en Duin, The Netherlands.
Summary
Phenytoin may cause reversible peripheral neuropathy, but clear neurotoxicity is rare. This drug
Area of Science:
- Neuroscience
- Pharmacology
- Neurology
Background:
- Phenytoin, an established antiepileptic drug, has a long history of use.
- While its neuroprotective potential is being explored for conditions like multiple sclerosis, peripheral neuropathy has been noted as an adverse event.
- The relationship between phenytoin and peripheral nerve health requires further clarification.
Purpose of the Study:
- To review the existing literature on phenytoin-induced peripheral polyneuropathy.
- To assess the evidence for neurotoxicity and reversibility of neuropathy associated with phenytoin use.
- To explore the pharmacological mechanisms potentially underlying phenytoin's effects on peripheral nerves.
Main Methods:
- Comprehensive literature review of case reports and series concerning phenytoin and peripheral neuropathy.
- Analysis of pharmacological data related to phenytoin's mechanism of action on voltage-gated sodium channels.
- Evaluation of evidence for causality, toxicity, and reversibility in reported cases.
Main Results:
- Evidence suggests a possible association between oral phenytoin use and reversible peripheral polyneuropathy.
- Clear neurotoxicity is rare, typically linked to prolonged high-dose or high-plasma level exposure.
- One case reported reversible chronic phenytoin intoxication with axonal atrophy and demyelination/remyelination.
Conclusions:
- Phenytoin is unlikely to cause irreversible peripheral nerve toxicity.
- Reversible polyneuropathy associated with phenytoin is plausible due to its effects on sodium channels.
- Further detailed case studies are needed to establish a definitive causal link for phenytoin-induced peripheral polyneuropathy.
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