Cerebellar degeneration following long‐term phenytoin therapy

Ghatak, Nitya R.; Santoso, Rudy; McKinney, William Mark

doi:10.1212/wnl.26.9.818

Cited by 106 publications

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“…Second, bilateral cerebellar damage is a frequent finding in MTLE and has previously been associated with disease chronicity . The relationship between cerebellar volume loss and phenytoin use has long been described in patients with TLE (Ghatak et al, 1976. Although we attempted to evaluate this relationship in our study, some patients were not able to provide a complete medication history.…”

Section: Discussionmentioning

confidence: 99%

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

et al. 2008

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Purpose-To determine the validity and utility of using automated subcortical segmentation to identify atrophy of the hippocampus and other subcortical and cerebellar structures in patients with mesial temporal lobe epilepsy (MTLE). Methods-VolumetricMRIs were obtained on 21 patients with MTLE (11 right, 10 left) and 21 age-and gender-matched healthy controls. Labeling of subcortical and cerebellar structures was accomplished using automated reconstruction software (FreeSurfer). Multivariate analysis of covariance (MANCOVA) was used to explore group differences in intracranial-normalized, ageadjusted volumes and structural asymmetries.Step-wise discriminant function analysis was used to identify the linear combination of volumes that optimized classification of individual subjects.Results-Results revealed the expected reduction in hippocampal volume on the side ipsilateral to the seizure focus, as well as bilateral reductions in thalamic and cerebellar gray matter volume. Analysis of structural asymmetries revealed significant asymmetry in the hippocampus and putamen in patients compared to controls. Discriminant function analysis revealed that patients with right and left MTLE were best distinguished from one another using a combination of subcortical volumes that included the right and left hippocampus and left thalamus (91-100% correct classification using cross-validation).Discussion-Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from previous studies based on manual tracings. Our data suggest that automated segmentation can provide a clinically useful means of evaluating the nature and extent of structural damage in patients with MTLE and may increase diagnostic classification of patients, especially when hippocampal atrophy is mild.

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Section: Discussionmentioning

confidence: 99%

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

et al. 2008

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“…Some differences between published results of morphometric studies might be related to interindividual differences associated with treatment of epilepsy-related loss of Purkinje cells [Ghatak et al 1976, Rapport and Shaw 1977, regional loss in response to chronic traumatic brain injury , neuronal loss associated with enhanced lipofuscin accumulation and oxidative stress (Table 7), and premortem changes related to the mechanism of death. Detailed neuropathological examination in this project excluded 5 autistic and 4 control cases with premortem and perimortem neuronal loss, as well as with severe autolytic changes to reduce the risk of distortion of results of morphometric studies.…”

Section: Discussionmentioning

confidence: 99%

“…Purkinje cell death is observed throughout the anterior and posterior lobes and in the flocculus/nodulus [Ghatak et al 1976, Rapport andShaw 1977]. Phenytoin exposure produces ataxia, dysarthria, hypotonia, and intenion tremor [Ghatak et al 1976, McLain et al 1980. Absence of these symptoms may help to exclude phenytoin as a potential cause of Purkinje cell loss in autistic subjects with a history of phenytoin treatment .…”

Section: Discussionmentioning

confidence: 99%

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

Węgiel¹,

Brown²

2013

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“…Seu uso, entretanto, não é isento de efeitos adversos, sendo o mais comum a disfunção cerebelar após intoxicação aguda, levando a sintomas como diplopia e ataxia. Atrofia cerebelar irreversível pode ocorrer após intoxicação aguda 2 e também após o uso crônico da fenitoína [3][4][5][6][7] . Estudos anteriores indicam que a atrofia cerebelar devido ao efeito tóxico direto da droga sobre as células de Purkinje ou pela hipóxia causada pelas crises generalizadas tônico-clônicas [3][4][5][6][7] , ou por esses dois fatores atuando sinergicamente [8][9][10][11] .…”

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Relação dose-dependente do uso crônico de fenitoína e atrofia cerebelar em pacientes com epilepsia

Negro¹,

Dantas²,

Zanardi

et al. 2000

Arq. Neuro-Psiquiatr.

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RESUMO -O uso crônico da fenitoína ou intoxicação aguda por essa droga produzem lesão cerebelar permanente com atrofia do vermis e hemisférios cerebelares, que pode ser evidenciada através de exames de neuroimagem. O objetivo deste estudo foi avaliar a correlação entre a dosagem e o tempo de uso da fenitoína com a ocorrência de atrofia cerebelar. Foram realizados levantamento de prontuários para a obtenção de dados clínicos e análise de tomografias de crânio para avaliação de atrofia cerebelar. Dos 66 pacientes estudados, 18 apresentaram atrofia moderada a severa, 15 atrofia leve e 33 foram considerados normais. Os pacientes com atrofia cerebelar moderada a severa foram aqueles com maior exposição à fenitoína (uso prolongado e dose total), apresentando diferença estatisticamente significativa se comparados aos pacientes com atrofia leve ou sem atrofia (p=0.02). Além disso, no subgrupo de pacientes em uso de fenitoína, aqueles com atrofia moderada a severa possuíam níveis séricos de fenitoína significativamente mais elevados que os pacientes com atrofia leve ou sem atrofia (p=0.008). Não houve relação entre duração do tratamento e dose de outros anticonvulsivantes e presença e grau de atrofia cerebelar. Os pacientes mais velhos apresentaram maior grau de atrofia cerebelar, indicando que o fator idade ou tempo de epilepsia, ou ambos, pode ser importante na determinação de degeneração cerebelar. Concluímos que apesar da possibilidade de lesão cerebelar relacionada a crises epilépticas repetidas, a contribuição da fenitoína pode ser claramente estabelecida como um dos determinantes da atrofia cerebelar, sobretudo naqueles pacientes com altas doses por tempo prolongado e níveis séricos elevados. PALAVRAS-CHAVE: fenitoína, atrofia cerebelar, epilepsia. Dose-related cerebellar atrophy in patients with epilepsy using phenytoinABSTRACT -The chronic treatment with phenytoin or the acute intoxication by this drug may cause permanent cerebellar injury with atrophy of cerebellum vermis and hemispheres, which can be detected by neuroimaging studies. The aim of the present study was to investigate the correlation between the dosage and duration of treatment with phenytoin and the occurrence of cerebellar atrophy. Sixty-six patients were studied and had their tomographies analyzed for cerebellar atrophy. Of the 66 patients studied, 18 had moderate/severe atrophy, 15 had mild atrophy and 33 were considered to be normal. The patients with moderate/severe atrophy were those with higher exposure to phenytoin (longer duration of treatment and higher total dosage) showing statistically significant difference when compared to patients with mild atrophy or without atrophy (p=0.02). Further, the patients with moderate/severe atrophy had serum levels of phenytoin statistically higher than those of patients with mild atrophy or without atrophy (p = 0.008). There was no association between other antiepileptic drugs dosage or duration of treatment and degree of cerebellar atrophy. We also found that older patients had cerebellar atrophy mor...

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Cerebellar degeneration following long‐term phenytoin therapy

Cited by 106 publications

References 0 publications

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

Relação dose-dependente do uso crônico de fenitoína e atrofia cerebelar em pacientes com epilepsia

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