Perampanel as adjunctive therapy in drug resistant epilepsy in adolescents and children waiting for epilepsy surgery: A multicenter observational study in Thailand.

PURPOSE: To evaluate the effectiveness and tolerability of perampanel (PER) in real-world settings in patients between 1 month and 18 years of age with drug resistant epilepsy (DRE) waiting for epilepsy surgery. METHODS: In this multicenter study, patients between 1 month and 18 years of age with DRE treated with PER between January 2020 and June 2021 were selected. The study outcome was effectiveness of PER treatment reported as reduction in seizure frequency and seizure freedom rate. Effectiveness was assessed at 30, 60, 90, 120, 150 and 180 days after initiation of PER. Tolerability profiles were reported as adverse events according to the observations of the patients' family members and physician. RESULTS: Eighty-five patients treated with PER were included in the study. The mean initial dose and mean maximum dose of adjunctive PER was 2 mg/day and 5.8 mg/day, respectively. The mean seizure frequency (rate/week) was 41.3, 25.4, 18.9, 14.3, 11.2, 11.1 and 8.9 seizures at baseline, 30, 60, 90, 120, 150 and 180 days, respectively; the reduction in the mean seizure frequency at all timepoints was significant compared at the baseline (p<0.001). At 180 days, ≥75% seizure reduction was seen in 64.9% (37/57) of the patients and seizure freedom was achieved in 36.8% (21/57). Drowsiness, ataxia, and behavioral changes were the common adverse events observed, and these improved after the dose of PER was reduced. No discontinuation of PER was required due to side effects or intolerance. CONCLUSION: In real-world settings, PER is well tolerated and effective in seizure control in pediatric and adolescent patients with DRE.

Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population.

Background: Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR). This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen (HLA) alleles in Thai patients. Methods: Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens-Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes. Results: The proportion of HLA-A∗02:07 and HLA-B∗15:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60-38.25; P = 0.013, and OR: 4.89; 95% CI: 1.28-18.67; P = 0.014]. In addition, subjects with HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83-37.41; P = 0.005, OR: 7.33; 95% CI: 1.63-33.02; P = 0.005; and OR: 10.29; 95% CI: 1.45-72.81; P = 0.029). In contrast to the LTG-induced MPE group, there were no significant differences between HLA alleles and LTG-induced SCAR group. Conclusion:HLA-A∗02:07 and HLA-B∗15:02 were associated with LTG-induced CADR in Thai patients. We also identified an association between HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed.

Autoimmune causes of encephalitis syndrome in Thailand: prospective study of 103 patients.

BACKGROUND: Data on encephalitis in Thailand have not been completely described. Etiologies remain largely unknown. We prospectively analyzed 103 Thai patients from 27 provinces for the causes of encephalitis using clinical, microbiological and neuroimaging indices; caseswithout a diagnosis were evaluated for autoimmune causes of encephalitis. METHODS: Patients with encephalitis and/or myelitis were prospectively studied between October 2010 and August 2012. Cases associated with bacterial, rickettsial and mycobacterial diseases were excluded. Herpes viruses 1-6 and enteroviruses infection was diagnosed using PCR evaluation of CSF; dengue and JE viruses infection, by serology. The serum of test-negative patients was evaluated for the presence of autoantibodies. RESULTS: 103 patients were recruited. Fifty-three patients (52%) had no etiologies identified. Twenty-five patients (24%) were associated with infections. Immune encephalitis was found in 25 (24%); neuropsychiatric lupus erythematosus (4), demyelinating diseases (3), Behcet's disease (1) and the remaining had antibodies to NMDAR (5), ANNA-2 (6), Yo (2), AMPA (1), GABA (1), VGKC (1) and NMDA coexisting with ANNA-2 (1). Presenting symptoms in the autoimmune group included behavioral changes in 6/25 (versus 12/25 in infectious and 13/53 in unknown group) and as psychosis in 6/25 (versus 0/25 infectious and 2/53 unknown). Seizures were found in 6/25 autoimmune, 4/25 infectious and 19/53 unknown group. Two patients with anti-ANNA-2 and one anti-Yo had temporal lobe involvement by magnetic resonance imaging. Two immune encephalitis patients with antibodies to NMDAR and ANNA-2 had ovarian tumors. CONCLUSIONS: Autoantibody-associated encephalitis should be considered in the differential diagnosis and management algorithm regardless of clinical and neuroimaging features.

Cerebellar hemorrhage after supratentorial surgery for treatment of epilepsy: report of two cases.

Hemorrhage occurring at regions remote from the operative site is an infrequent complication. Although the mechanism remains unclear, previous reports implicate over drainage of cerebrospinal fluid as the predominant mechanism. The authors report two cases of cerebellar hemorrhage after supratentorial surgery. Two young patients underwent left hemispherectomy and fronto-temporal resection for the treatment of refractory hemispheric and multiregional epilepsy. The hemorrhage manifested early in the immediate postoperative period as delayed awakening. The diagnosis was established by computed tomography. Treatment consisted in external ventricular drainage in case 1 and conservative treatment in case 2. Both patients recovered without major neurological deficits. Early detection and awareness of this complication may help to avoid further neurological morbidity and mortality.

The first invasive EEG monitoring for surgical treatment of epilepsy in Thailand.

The authors report the first invasive electroencephalography (EEG) monitoring in Thailand in a patient who had intractable left temporal lobe epilepsy. The seizure origin and functioning cortices were identified The corresponding epileptogenic zone was resected without functional deficit. The patient has become seizure free 1 year since surgery. Subdural EEG monitoring with cortical stimulation have been developed at this tertiary epilepsy center The technique provides essential evidence for the surgical decision so that the best post operative outcome can be achieved.

Quality of life after successful epilepsy surgery: evaluation by occupational achievement and income acquisition.

OBJECTIVES: A comprehensive epilepsy surgery program has been developed at Chulalongkorn University Hospital, Thailand to reach an international standard level, rendering patients good surgical outcomes comparable to developed countries. After successful operation, seizure free patients have become independent, self earning or employed. However, quality of life (QOL) in terms of occupational achievement and income acquisition after epilepsy surgery has never been studied. These indicators reflect the ultimate QOL in the aspects of actual independency, intact brain functions, mental health and psycho-social interactions. The authors therefore conduct the study on improvement of QOL after successful epilepsy surgery using these parameters. MATERIAL AND METHOD: One hundred and eleven intractable epilepsy who have become seizure free to worthwhile improved (Engel class I to III) after standard presurgical evaluation and epilepsy surgery from January 2002 to December 2004 were evaluated. The patients were followed up for 3 years. The occupational status and incomes were categorized according to the ranking of the patients' functioning levels. The pre and post surgery work abilities, employment and incomes were interviewed and compared. Mc Nemar test and paired t-test were used for statistical analyses. RESULTS: The average age of the 111 adults (54 males and 57 females) was 33.7 +/- 9.2 years. Eighty two percent of the patients had temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and underwent standard anterior temporal lobectomy. The rest had tumors, cortical dysplasia or scar and received lesionectomy or cortical resection assisted by intra-operative or intra-cranial EEG. The overall seizure free rate is 83.8%. The occupational status of the subjects was shown to improve significantly after surgery from unemployed to higher categories of professional achievement (p < 0.001). The number of unemployed and no income individuals decreased from 66 to 25 cases (62.1% reduction rate) after surgery (p < 0. 001). Reciprocally, the number of persons who achieved professional jobs with regular incomes or salaries increase from 30 to 53 cases (43.4% increasing rate) (p < 0.001). The patients who have not acquired any income increment showed improvement in working ability after epilepsy surgery. The average annual incomes per capita shows the increasing rate of 45.08%, from 55,657.85 Baht (approximately U.S. dollars 1390) to 80,748.15 Baht (approximately U.S. dollars 2018), with strong statistical significance (p < 0.001). The improvement is best seen in seizure free than in non-seizure free subjects. CONCLUSION: The present study, to the authors 'knowledge, is the first to use work abilities, professional achievement and income acquisition to assess the ultimate QOL after epilepsy surgery. Most subjects have been shown to significantly improve their postoperative lives in terms of occupational accomplishment and income increment, especially in seizure free individuals. The need for expansion of epilepsy surgery is emphasized.