Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.
We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.
Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.
Video-EEG telemetry is often used to support the diagnosis of non-epileptic seizures (NES). Although rare, some patients may have both epileptic seizures (ES) and NES. It is crucially important to identify such patients to avoid the hazards of inappropriate anticonvulsant withdrawal. To delineate the electroclinical characteristics and diagnostic problems in this group of patients, we studied the clinical, EEG and MRI features of 14 consecutive patients in whom separate attacks, considered to be both NES and ES were recorded using video-EEG telemetry. Only two patients were drug-reduced during the telemetry. Most patients had their first seizure (ES or NES) in childhood (median age 7 years; range: 6 months-24 years); 8/14 patients were female. Brain MRI was abnormal in 10/14 patients. Interictal EEG abnormalities were present in all patients; 13/14 had epileptiform and 1/14 only background abnormalities. Over 70 seizures were recorded in these 14 patients: in 12/14 patients, the first recorded seizure was a NES (p < 0.001), and 7 of these patients had at least one more NES before an ES was recorded. Only 3/14 patients had more than 5 NES before an ES was recorded. Recording a small number of apparently NES in an individual by no means precludes the possibility of additional epilepsy. Particular care should be taken, and multiple (> 5) seizure recording may be advisable, in patients with a young age of seizure onset, interictal EEG abnormalities, or a clear, potential aetiology for epilepsy.
To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247 ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.
Evaluating the candidacy for epilepsy surgery in patients with tuberous sclerosis can be challenging, particularly when non-invasive investigations do not show a clear epileptogenic zone. Stereoencephalography may be useful in such cases. We present a case in which the primary epileptogenic tuber was successfully identified by stereoencephalography, which resulted in seizure freedom following epilepsy surgery. [Published with video sequences].
We examined the clinical, semiological, scalp EEG, and neuropsychological features of patients with "pure" neocortical temporal lobe epilepsy (NTLE) who were successfully treated by neocortical temporal resection sparing the mesial temporal structures. This retrospective study included 17 patients with lesional NTLE who satisfied the following criteria: presence of a discrete structural lesion in the lateral temporal lobe on preoperative MRI; lateral temporal resection sparing the mesial temporal structures; follow-up for at least two years after surgery; and favourable postoperative seizure outcome (Engel Class I). The study included 10 females and seven males, and the age at surgery ranged from 15 to 48 years (mean: 30.7 years). Auras, video-recorded seizure semiology, interictal and ictal EEG, and pre- and post-operative neuropsychological data were reviewed. Twenty patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, who had a favourable postoperative seizure outcome (Engel Class I), were selected as a control group. Age at seizure onset was significantly greater in patients with NTLE than in controls. A history of febrile convulsion was significantly less frequent in NTLE patients. Epigastric ascending sensation (6% versus 40%; p=0.017), oral automatisms (29% versus 80%; p=0.003), gestural automatisms (47% versus 80%; p=0.047), and dystonic posturing (0% versus 40%; p=0.003) were significantly less frequent in NTLE than controls. Ictal unitemporal rhythmic theta activity was also significantly less frequent in NTLE than controls (35.3% versus 75%; p=0.015). Preoperative IQ score (range: 68 to 114; mean: 88.9) and preoperative memory quotient score (range: 56-122; mean: 98.1) were significantly higher in NTLE (p=0.003 and p=0.048, respectively). There were notable differences in clinical, semiological, EEG, and neuropsychological features between "pure" NTLE and MTLE. These findings may be useful to identify the epileptogenic zone.
Super-refractory status epilepticus (SRSE) is a neurocritical emergency, associated with significant morbidity and mortality. The precise pathophysiology is still not completely understood. The likelihood of spontaneous seizure termination reduces with time, and it is of paramount importance to abort status in order to prevent permanent long-term neurological sequelae and death. A few neuroprotective strategies, such as general anaesthesia, steroids, ketogenic diet and hypothermia, have been used to treat SRSE, however, the clinical outcome remains inconclusive. We herein present two cases of SRSE, which were successfully treated with electroconvulsive therapy (ECT) after failing all pharmacological measures.