Cerebellar Atrophy in Patients With Long-term Phenytoin Exposure and Epilepsy

Ney, Gershon C.; Lantos, George; Barr, William; Schaul, Neil

doi:10.1001/archneur.1994.00540200043014

Cited by 105 publications

(60 citation statements)

References 27 publications

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“…Generalized CA, rather than unilateral or asymmetric CA, was observed in our patients with intractable nonlesional temporal lobe epilepsy. This finding seems to suggest that the pathogenesis of the CA is related either to long-term exposure to AEDs (1,4) or to the effects of repeated bilateral excitotoxicity at the cerebellar hemispheres, such as may occur in generalized seizures. The findings of this study also suggest that the presence of CA does not influence the surgical outcome of tempoyal lobectomy.…”

Section: Discussionmentioning

confidence: 97%

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Significance of Cerebellar Atrophy in Intractable Temporal Lobe Epilepsy: A Quantitative MRI Study

et al. 2000

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Summary: Purpose: To determine the incidence of cerebellar atrophy (CA) in patients with intractable temporal lobe epilepsy, whether any clinical factors are significantly associated with CA, whether CA is unilateral or asymmetric and whether this feature has any relationship to the side of epileptogenicity, and whether the presence of CA is related to epilepsy surgery outcome.Methods: We developed a magnetic resonance imaging method of measuring the presurgical volumes of the cerebellar hemispheres of 185 patients who underwent temporal lobectomy for intractable epilepsy and of 80 control subjects. In addition, cerebellar volumes were normalized to the total brain volumes. CA was determined as being present when the measured volume was smaller than two standard deviations from the mean value found in control subjects.Results: Both absolute and normalized cerebellar volumes were found to be significantly reduced in the epilepsy patients compared with the control subjects. Without normalization of

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Section: Discussionmentioning

confidence: 97%

“…Previous studies suggested that the incidence of CA in epilepsy patients was approximately 30% (4,5). However, until this study, no work had quantitatively measured the cerebellar volumes in patients with nonlesional intractable temporal lobe epilepsy.…”

Section: Discussionmentioning

confidence: 98%

Significance of Cerebellar Atrophy in Intractable Temporal Lobe Epilepsy: A Quantitative MRI Study

et al. 2000

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“…7,8 We used phenobarbital as a primary medication in neonatal seizure when both clinical and electrical evidence of seizures was evident. Both the seizures and the AED medication may cause cerebellar atrophy-either synergistically 35 or independently 36 -during the development of the cerebellum. Abnormalities of the cerebellum in mice after exposure to phenobarbital, such as a decrease in the number of Purkinje 37 and granular cells, 33 without an effect on the area of the cerebellum, have been reported.…”

Section: Discussionmentioning

confidence: 99%

Brain MRI Measurements at a Term-Equivalent Age and Their Relationship to Neurodevelopmental Outcomes

Park

Yoon

Han³

et al. 2013

AJNR Am J Neuroradiol

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“…Phenytoin administration has been reported to be associated with cerebellar atrophy and persistent cerebellar ataxia with clinical manifestation presenting as confusion, slurred speech and nastagmus following acute and longterm intoxication (Imamura et al, 1992;Ney et al, 1994) and temporal cerebellar atrophy following phenytoin therapy (Guerrero et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

The Role of Antioxidants in Cerebellar Development: A Review of Literature

Imosemi¹

2013

Int. J. Morphol.

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SUMMARY: Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reacting oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction, and that the embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. ROS can oxidize molecular targets such as DNA, protein, lipid in a process called oxidative stress resulting in cellular dysfunction and in utero death or teratogenicity. This review, consisting of literature search of journals and chapters in books aims at highlighting the importance of the cerebellum in controlling various motor activities in the body, as well as substances affecting cerebellar development with a view of providing an insight to the role antioxidants play in cerebellar development. It is interesting to note that the developing brain (especially the cerebellum, cerebrum and hippocampus) is highly vulnerable to the deleterious effects of ROS. Studies have shown that exposure to oxidants in the first trimester is associated with an increased risk of major congenital anomalies, as most vital organs in the body develop and some become functional within this period in offspring. Antioxidants may prevent oxidative damage in degenerative diseases including ageing, cardiovascular diseases, cancer, Alzheimer's disease, stroke and Parkinson's disease as such play a critical role in wellness and health maintenance. INTRODUCTIONThe consumption of some drugs and chemical substances at various doses could cause malformations in certain developing body organs especially when used during critical periods of development. Such malformations could reflect in the gross and microscopic appearances of affected organs in the mature organisms (Moore & Persaud, 1998). The critical stages of development at which such malformations occur in mammals correspond to the pre-natal and early postnatal lives. In the former circumstance, these substances when consumed by the mother, affect the embryos or foetus only if they cross the blood placental barrier. In the latter circumstance, the substances need to have been administered directly to the neonates or suckled in the breast milk in early post-natal life for them to affect development (Moore & Persaud).The cerebellum is a highly organized structure in which the Purkinje cells (Pc) are the sole output of the cerebellar cortex (Altman, 1969(Altman, , 1972a(Altman, , 1972b(Altman, , 1972c, and it is one of the first structure of the brain to differentiate, however, it achieves its mature configuration many months after birth (Wang & Zoghbi, 2001;Bouet et al., 2005). For this reason, the cerebellum is especially vulnerable to developmental irregularities on exposure to oxidants which generate free radicals resulting in oxidative stress (Wang & Zoghbi;Kern & Jones, 2006). Oxidative stress occurs due to an imbalance in pro-oxidant and antioxidant levels. Scientific evidence sugg...

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Cerebellar Atrophy in Patients With Long-term Phenytoin Exposure and Epilepsy

Cited by 105 publications

References 27 publications

Significance of Cerebellar Atrophy in Intractable Temporal Lobe Epilepsy: A Quantitative MRI Study

Significance of Cerebellar Atrophy in Intractable Temporal Lobe Epilepsy: A Quantitative MRI Study

Brain MRI Measurements at a Term-Equivalent Age and Their Relationship to Neurodevelopmental Outcomes

The Role of Antioxidants in Cerebellar Development: A Review of Literature

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