The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy

 

Purpose: Phenytoin is known to be able to induce cerebellar atrophy in patients with epilepsy. It is also known that a CYP2C9 mutation (*2 or *3) reduces phenytoin metabolism by 25 50% and can increase the risk of phenytoin related side effects. We examined the influence of CYP2C9 polymorphisms on total cerebellar volume and cerebellar gray and white matter volumes in patients with epilepsy taking phenytoin.

Methods: For the genotyping, 100 adult patients with documented epilepsy who had been taking phenytoin for >1 year were selected. From this group, we randomly selected 19 mutant individuals (MT group; CYP2C9*2 and *3) for a whole brain volume measurement using MRI and 19 wild type individuals (group WT; CYP2C9*1) with similar clinical and demographic characteristics to those in the MT group for comparison.

Total intracranial volume measurements were used to normalize the acquired volumes, which were separated into gray matter volume, white matter volume, and total volume.

Results: The MT group exhibited a significant reduction in cerebellar white matter volume (p 0.002) but not in total cerebellar volume.

Conclusion: Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.


More Harm Than Good: Antiseizure Prophylaxis After Traumatic Brain Injury Does Not Decrease Seizure Rates but May Inhibit Functional Recovery

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Background: The purposes of this study were to examine the current Brain Trauma Foundation recommendation for antiseizure prophylaxis with phenytoin during the first 7 days after traumatic brain injury (TBI) in preventing seizures and to determine if this medication affects functional recovery at discharge.

Methods: The records of adult (age ≥ 18 years) patients with blunt severe TBI who remained in the hospital at least 7 days after injury were retrospectively reviewed from January 2008 to January 2010. Clinical seizure rates during the first 7 days after injury and functional outcome at discharge were compared for the two groups based on antiseizure prophylaxis, no prophylaxis (NP) versus phenytoin prophylaxis (PP). Statistical analysis was performed using χ2.

Results: A total of 93 adult patients who met the previously mentioned criteria were identified (43 [46%] NP group vs. 50 [54%] PP group). The two groups were well matched. Contrary to expectation, more seizures occurred in the PP group as compared with the NP group; however, this did not reach significance (PP vs. NP, 2 [4%] vs. 1 [2.3%], p = 1). There was no significant difference in the two groups (PP vs. NP) as far as disposition are concerned, mortality caused by head injury (4 [8%] vs. 3 [7%], p = 1), discharge home (16 [32%] vs. 17 [40%], p = 0.7), and discharge to rehabilitation (30 [60%] vs. 23 [53%], p = 0.9). However, with PP, there was a significantly longer hospital stay (PP vs. NP, 36 vs. 25 days, p = 0.04) and significantly worse functional outcome at discharge based on Glasgow Outcome Scale (GOS) score (PP vs. NP, 2.9 vs. 3.4, p < 0.01) and modified Rankin Scale score (2.3 ± 1.7 vs. 3.1 ± 1.5, p = 0.02).

Conclusion: PP may not decrease early posttraumatic seizure and may suppress functional outcome after blunt TBI. These results need to be verified with randomized studies before recommending changes in clinical practice and do not apply to penetrating trauma.