Zonisamide‐Related Confusional State with Prolonged Diffuse Slow‐Wave Bursts: A Case Report.
Authors: Yoshino Aihide , Kimura Kazuya 
Published: August 2005

Purpose: Zonisamide (ZNS; I,2‐benzisoxazolc‐3‐methane‐ sulfonamide) may be associated with schizophrenia‐like psychosis, hyperkinesia, or mania. However, no reports have noted a ZNS‐induced confusional state associated with worsening of electroencephalogruphic (EEG)abnormalities. We report a patient receiving a therapeutic dose of ZNS who developed diverse cognitive and behavioral disorders, including clouding of consciousness, that disappeared after discontinuation of ZNS. The EEG, which showed continuous diffuse slow‐wave bursts, markedly but temporarily improved with intravenous diazepam administration. Case Reporr: A 24‐year‐old woman with an 8‐year history oftemporal lobe epilepsy was admitted to our hospital because of generalized tonic‐clonic convulsions (GTC) due to noncompliance. Her interictal EEG showed focal 6‐Hz spike‐wave complexes independently over the left and right temporal region. Magnetic resonance imaging showed normal appearance of the brain. We instituted 500 mg of ZNS and 600 mg of CBZ per day. She showed normal behavior and cognition until hospital day 4, when psychomotor retardation and emotional instability appeared. She could not perform subtraction or recall a 5‐digit number. Her EEG intermittently revealed frontally dominant diffuse 2 to 4‐Hz high voltage slow‐wave bursts lasting <20 minutes. The slow‐wave bursts followed a sudden onset of bilateral synchrony. When 20 mg of diazepam was administered intravenously, the slow wave bursts mark‐ edly but temporarily improved. Although PHT was added, her confu‐ sional state and EEG patterns did not improve. Serum ZNS, CBZ, and PHT concentrations were 23.3 kg/mL, 4.3 yg/mL, and 7.8 pg/mL, respectively. On the 13th hospital day, ZNS administration was discontinued. By day 15 she had fully recovered and the EEG showed no diffuse slow‐wave bursts. She remained partially amnesic for the events after admission. Conclusions: Because some patients with complex partial seizure (CPS) may develop a psychotic state after a lucid interval of several days following GTC, the cognitive disorder that our patient developed might similarly have been associated with GTC. However, because postictal psychosis typically is not associated with slow‐wave bursts in the EEG, a different explanation is required in the present case. Other case reports have documented prolonged confusion followed GTC due to nonconvulsive status epilepticus (NCSE). However, all of these cases showed NCSE immediately after GTC without a lucid interval. Therefore, we concluded that the patients confusional state most likely was not caused by GTC but instead was related to ZNS administration. Because the serum ZNS concentration did not reach a toxic level, any adverse effects apparently arose at a therapeutic ZNS dose. The patients EEG showed prolonged diffuse slow‐wave bursts con‐ sistent with either toxic encephalopathy or NCSE, the latter being strongly favored by the observation that intravenous diazepam markedly improved the EEG. The diazepam effect was only temporary because, while intravenous diazepam is short‐acting, significant ZNS levels and activity remained in the patients brain. We can hypothesize 2 possib es as to relationships between ZNS and NCSE in this patient: ZNS exacerbating her usual CPS to result in NCSE; and ZNS inducing generalized NCSE unrelated to her usual seizures. The patient's EEG during NCSE, however, differed from typical ictal discharges of CPS in showing regional epileptic discharges or secondary bilateral synchrony. Some cases with generalized NCSE may show diffuse slow‐wave activity resembling that in the present case. Consequently, we could not exclude the possibility that ZNS induced generalized NCSE rather than being related to her usual seizures. Interestingly, it has been reported that tiagabine also may induce generalized NCSE in patients with localization‐related epilepsies.