Authors :
Presenting Author: Hideo Kato, MD – National Center of Neurology and Psychiatry Hospital
Go Taniguchi, MD, PhD – National Center of Neurology and Psychiatry
Yoko Shigemoto, MD, PhD – National Center of Neurology and Psychiatry
Keisuke Takahata, MD, PhD – Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology
Harumasa Takano, MD, PhD – National Center of Neurology and Psychiatry
Eiji Nakagawa, MD, PhD – National Center of Neurology and Psychiatry
Rationale:
This case report examines the relationship between antiseizure medication (ASM)-induced cognitive impairment and changes in resting cerebral glucose metabolism. Although there are some reports on the impact of ASM on cerebral glucose metabolism, studies specifically exploring its relationship with cognition and behavior are scarce. We performed FDG-PET before and after medication adjustment in a patient with generalized epilepsy and reported the findings, including their relationship to cognitive decline.Methods:
Informed consent was obtained, and a chart review was conducted.
Results:
A 22-year-old man presented to our hospital for evaluation of refractory epilepsy. His seizures began at the age of 17, characterized by twitching around the mouth and generalized convulsions. He was diagnosed with focal epilepsy and was treated with Zonisamide (ZNS) 500 mg, Carbamazepine (CBZ) 400 mg, and Lacosamide (LCM) 200 mg. Following the initiation of ZNS, he began to feel difficulty with speech and cognitive slowing. Video-EEG monitoring captured perioral myoclonia with generalized spikes. Brain MRI was normal, but interictal FDG-PET showed slight hypometabolism in the left inferior frontal gyrus. Neuropsychological tests revealed impairments in psychomotor speed, fluency, and attention, with a Digit Span (DGS) of forward 4 / reverse 4, Trail Making Test (TMT) times of 31 / 82 seconds (part A / B), and fluency scores of 20 words for initial letters (shi-, i-, and re-) and 3 words for category (animal). He was diagnosed with perioral myoclonia with absences, and CBZ and LCM were replaced with Levetiracetam (LEV). ZNS was discontinued due to suspected cognitive side effects. Cognitive impairment improved after ASM adjustment, with DGS forward 7 / reverse 5, TMT 51 / 51 seconds (part A / B), initial word fluency of 28 words, and category word fluency of 12 words. A follow-up FDG-PET showed improvement in the hypometabolism of the left inferior frontal gyrus.The cognitive impairment observed in this case aligns with the profile of cognitive adverse effects of ZNS1. fMRI studies in patients taking ZNS have shown decreased activation in the cognitive frontal and parietal networks2. Although we cannot exclude scan-scan variability in this limited report, the observed glucose metabolism reduction may be related to drug-induced cognitive impairment.
Conclusions:
The brain metabolism changes observed may explain the clinical symptoms and could have been induced by ASM. Particularly concerning cognitive impairment, the impact of ASM on FDG-PET findings warrants further investigation.
< References >
1) Park SP, Hwang YH, Lee HW, Suh CK, Kwon SH, Lee BI. Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients. Epilepsy Behav. 2008 Jan;12(1):102-8.
2) Wandschneider B, Burdett J, Townsend L, Hill A, Thompson PJ, Duncan JS, Koepp MJ. Effect of topiramate and zonisamide on fMRI cognitive networks. Neurology. 2017 Mar 21;88(12):1165-1171.
Funding: none