Phenytoin cerebellar degeneration

Last revised by Dr Yahya Baba on 03 Jan 2021

Phenytoin cerebellar atrophy occurs after prolonged exposure to phenytoin, usually for the management of epilepsy. 

The most important factor in the development of cerebellar atrophy is the duration of phenytoin exposure 2. Approximately 30% of individuals with long-term phenytoin exposure will develop cerebellar atrophy 2

Acute phenytoin toxicity can result in transient cerebellar dysfunction, but it is chronic exposure to therapeutic levels of phenytoin which results in permanent pancerebellar dysfunction, including ataxia, nystagmus, dysarthria, and hypotonia 2

Histological assessment demonstrates loss of Purkinje cells throughout the cerebellum, as well as less marked loss of internal granular layer cells 1

CT and MRI are able to demonstrate generalized cerebellar volume loss. A clue to the diagnosis is the commonly associated calvarial thickening also due to long-term phenytoin exposure. 

This differential is essentially that of other causes of diffuse cerebellar atrophy

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Cases and figures

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