Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics

Shanmugarajah, Priya; Hoggard, Nigel; Aeschlimann, Daniel; Aeschlimann, Pascale; Dennis, Gary; Howell, Stephen; Reuber, Markus; Grünewald, Richard A.; Hadjivassiliou, Marios

doi:10.1016/j.seizure.2018.01.019

Cited by 18 publications

(10 citation statements)

References 26 publications

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“…Yet, EA may be underestimated and insufficiently reported in patients with SCN2A epileptic and developmental encephalopathy possibly because ataxia is harder to identify in severely handicapped patients. In addition, persistent ataxia is known as secondary adverse event during medication with phenytoin, 14,15 it is therefore challenging to disentangle the causality between the pathogenic SCN2A variant and ataxia in encephalopathic patients under multi-drug treatment. Four of our patients showed divergent signs of intellectual impairment: while Patient 16 showed an IQ of 71 with particular impairment in her speech development, 5 Patient 17 showed traits of autism spectrum disorder.…”

Section: Discussionmentioning

confidence: 99%

“…We excluded a few reported patients with permanent ataxia, which has been described as potential secondary effect of chronic pharmacological treatment with phenytoin and other anti-convulsive medications. 14,15 The frequency of episodes differs between daily in two cases (Patients 1 and 18), weekly to monthly in most cases (Patients 2e4, 6e13, 19e21), and at most 1e3 episodes every year in Patients 5 and 14e17 (Tables 1 and 2).…”

Section: Episodic Ataxia: Phenotypementioning

confidence: 99%

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Clinical and genetic spectrum of SCN2A-associated episodic ataxia

Schwarz

Bast

Gaily

et al. 2019

European Journal of Paediatric Neurology

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Section: Discussionmentioning

confidence: 99%

Section: Episodic Ataxia: Phenotypementioning

confidence: 99%

Clinical and genetic spectrum of SCN2A-associated episodic ataxia

Schwarz

Bast

Gaily

et al. 2019

European Journal of Paediatric Neurology

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“…Phenytoin may bind to the active state of the sodium ion channels to prolong the rapid inactivation of the channel [ 129 ], which reduces the repetitive firing of action potentials. Blocking the sodium channel may decrease the sensitivity of the neuronal cell to epileptogenic stimuli by increasing the membrane threshold for depolarization [ 130 ].…”

Section: Broad and Narrow Spectrum Anti-seizure Drugsmentioning

confidence: 99%

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Akyüz

Köklü

Ozenen

et al. 2021

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: Over the decades, various interventions have been developed and utilized to treat epilepsy. However, majority of epileptic patients are often first prescribed with anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as a first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action including regulation of ion channels, blocking of glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggest that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile, by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.

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“…There is no correlation between the degree of atrophy, the severity of clinical symptoms, and the drug serum levels. 9 In a study done by Shanmugarajah et al, 10 cerebellar ataxia was present in 40% of patients with epilepsy and chronic exposure to phenytoin.…”

Section: Discussionmentioning

confidence: 96%

Irreversible Cerebellar Atrophy as a Complication of Short-Term Phenytoin Exposure: Clinical Improvement Following Discontinuation of the Culprit

Algahtani¹,

Shirah²,

Alqahtani³

et al. 2020

J Epilepsy Res

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Phenytoin (diphenylhydantoin) is a widely used antiepileptic drug for controlling both generalized and partial seizures. Reversible cerebellar symptoms, including cerebellar ataxia, have been recognized as an adverse event of phenytoin use for many years. On the other hand, cerebellar degeneration has been reported with chronic use in an epileptic patient treated with this drug. We are reporting an interesting case of phenytoin induced acute pan-cerebellar syndrome with cerebellar atrophy on neuro-imaging that improved many years after discontinuation of the drug. Discontinuation of phenytoin may give a chance for the patient to recover slowly, months after stopping the drug. It is very important for the attending neurologist to educate the patients and their families on some common clinical manifestations suggestive of drug toxicity and perform a regular follow-up and clinical examination at regular intervals.

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Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics

Cited by 18 publications

References 26 publications

Clinical and genetic spectrum of SCN2A-associated episodic ataxia

Clinical and genetic spectrum of SCN2A-associated episodic ataxia

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Irreversible Cerebellar Atrophy as a Complication of Short-Term Phenytoin Exposure: Clinical Improvement Following Discontinuation of the Culprit

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