Pharmacogenetic screening of carbamazepine-induced severe cutaneous allergic reactions.

Recent studies associated the HLA-B 1502 allele with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients from China, Thailand and Malaysia. No association has been found in patients from Europe or Japan. Linkage summary reports from East and South-east Asia predict a highly significant odds ratio (OR) of 84.75 (95% confidence interval [CI]=42.53-168.91; p=8.96×10[-15]) with sensitivity and negative predictive values of 92% and 98%, respectively. The higher prevalence of HLA-B 1502 allele among certain Asian populations (10-15%) compared to Caucasians (1-2%) may explain a 10-fold to 25-fold higher incidence of CBZ-SJS/TEN in patients from Asia. Screening for HLA-B 1502 before using CBZ can prevent SJS/TEN in certain populations, but screening may be less beneficial in populations with low HLA-B 1502 allele frequency and in patients exposed to CBZ for more than 2 months. A retrospective study demonstrated that the costs of HLA-B 1502 screening were less than those of SJS treatment. This article reviews possible benefits and concerns of HLA-B 1502 screening in clinical practice.

Outcome of temporal lobectomy for hippocampal sclerosis in older patients.

Patients of 50 years or older account for a small but significant portion of the patient population that receives surgical treatment for epilepsy. There have been few studies reporting surgical outcomes from temporal lobectomy in older patients. We examined seizure outcome and surgical complications after anterior temporal lobectomy for temporal lobe epilepsy with pathological evidence of unilateral hippocampal sclerosis. Two patient groups were compared in this study: patients 50 years or older (mean age 55.5 years old, n=16) and patients less than 50 years old (mean age 32.9 years old, n=184). After a minimum of one year follow up, younger patients (79.4%, n=146) were significantly more likely to be seizure-free (p=0.041) compared to older patients (56.3%, n=9). There was no significant difference (p=0.404) between the two age groups in the percentage of patients withdrawn from medication following surgery. Surgical complications were significantly higher in the older age group compared to the younger age group (p=0.009), although there was no permanent morbidity. Thus, while surgical treatment of temporal lobe epilepsy with unilateral hippocampal sclerosis is still beneficial in older patients who are refractory to medical therapy, surgical treatment should be considered at as early an age as possible, to maximize the chance for a better outcome with fewer complications.

A study of knowledge and attitude improvement on epilepsy among Thai physicians and nurses.

OBJECTIVE: To study improvement ofknowledge and attitudes on epilepsy care among two groups ofphysicians and nurses. MATERIAL AND METHOD: Knowledge and attitudes of 164 physicians and 403 nurses before and after attending educational courses on epilepsy care was assessed using questionnaires. RESULTS: After the courses, knowledge and attitudes of physicians and nurses was improved with statistical significance (pair-t-test: t (163) = 10.19, p < 0.001; t (402) = 18.41, p < 0.001). The most misunderstanding were incorrectfirst aid of seizure, misinterpretation of blood changes after antiepileptic drug therapy inadequate awareness of epilepsy surgery, and prohibition of swimming in people with epilepsy No differences between baseline and post training scores among physicians in neurology internal medicine, emergency medicine, and general practice were observed. CONCLUSION: The present study is the first to objectively measure improvement of knowledge and attitudes among Thai physicians and nurses after courses about epilepsy care, reflecting importance of additional epilepsy education. Items showing misapprehension can be used to provide the educational contents.

Dynamic perfusion patterns in temporal lobe epilepsy.

PURPOSE: To investigate dynamic ictal perfusion changes during temporal lobe epilepsy (TLE). METHODS: We investigated 37 patients with TLE by ictal and interictal SPECT. All ictal injections were performed within 60 s of seizure onset. Statistical parametric mapping was used to analyse brain perfusion changes and temporal relationships with injection time and seizure duration as covariates. RESULTS: The analysis revealed significant ictal hyperperfusion in the ipsilateral temporal lobe extending to subcortical regions. Hypoperfusion was observed in large extratemporal areas. There were also significant dynamic changes in several extratemporal regions: ipsilateral orbitofrontal and bilateral superior frontal gyri and the contralateral cerebellum and ipsilateral striatum. CONCLUSION: The study demonstrated early dynamic perfusion changes in extratemporal regions probably involved in both propagation of epileptic activity and initiation of inhibitory mechanisms.

Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population.

PURPOSE: Previous studies found a strong association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations. Even in Han Chinese, the HLA-B*1502 was not associated with CBZ-induced maculopapular eruptions (MPE). This study seeks to identify whether HLA-B*1502 is associated with CBZ- or phenytoin (PHT)-induced SJS or MPE in a Thai population. METHODS: Eighty-one Thai epileptic patients between 1994 and 2007 from the Chulalongkorn Comprehensive Epilepsy Program were recruited. Thirty-one subjects had antiepileptic drug (AED)-induced SJS or MPE (6 CBZ-SJS, 4 PHT-SJS, 9 CBZ-MPE, 12 PHT-MPE), and 50 were AED-tolerant controls. RESULTS: For the first time, a strong association between HLA-B*1502 and PHT-induced SJS was found (p = 0.005). A strong association was also found between the HLA-B*1502 and CBZ-induced SJS (p = 0.0005), making Thai the first non-Chinese population demonstrating such an association. Some patients, who were HLA-B*1502 and suffered from CBZ-induced SJS, could be tolerant to PHT and vice versa. This suggests that HLA-B*1502 may be a common attribute required for a Thai patient to develop SJS from these two AEDs; other different elements, however, are also needed for each AED. In addition, no association between HLA-B alleles and CBZ- or PHT-induced MPE was found. CONCLUSIONS: CBZ- and PHT-induced SJS, but not MPE, is associated with HLA-B*1502 allele in Thai population.

Epilepsy and the law--a view from Thailand.

BACKGROUND: Patients with epilepsy often suffer social injustice in many societies. OBJECTIVE: This is a review of current laws dealing with epilepsy and the consequences of this complex disease. MATERIAL AND METHOD: The author looked at reported unjust legal and social acts resulting from epileptic seizures and their results. RESULTS: The author found that accusation of criminal acts, accidents while driving, and job loss are relatively common experiences for epileptics. Such events reflect lack of public understanding. There is inadequate legislation to protect epileptics. Most disturbing areas are ictal behavior misinterpreted as crime, driving while experiencing a seizure, and social discrimination. There is no law dealing with epilepsy in Thailand while considerable progress in this field has been made in Western countries. CONCLUSION: Epilepsy patients are inadequately protected by Thai law. There is an urgent need for education and campaigns for their rights focused on the public, the legal profession, and the health care professionals.

Successful resection of Hypothalamic Hamartoma with intractable gelastic seizures--by transcallosal subchoroidal approach.

A 19-year old female with intractable gelastic seizures was found to have 0.7 x 1.8 x 1.8 cm elliptical mass on the floor of the third ventricle. The signal intensity on the Magnetic Resonance Imaging (MRI) was consistent with the Hypothalamic Hamartoma (HH). Ictal EEG demonstrated rhythmic 7 Hz waves over Fp2, F4, and C4 with spreading to the right temporal region and then bilaterally. Ictal Single Photon Emission Computerized Tomography (SPECT) showed hyperperfusion at hypothalamic and medial frontopolar regions. The patient underwent surgical resection using Trans Callosal Subchoroidal Approach (TCSA) to the third ventricle. Pathological finding confirmed the diagnosis of hypothalamic hamartoma. Following the operation, she has been seizure free up to 12 months. Thereafter, provoked seizures seldom occurred and there has been improvement in her memory, emotional control and independence. This appears to be the first report of this surgical approach for HH, which is less likely to disturb memory function compared to previously described interfoniceal approach.

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.

Ring chromosome 20 with nonconvulsive status epilepticus: electroclinical correlation of a rare epileptic syndrome.

The electroclinical features of two Thai women with ring chromosome 20 and nonconvulsive status epilepticus (NCSE) were studied. Both have also had generalized tonic-clonic seizures and complex partial seizures of varying frequencies since adolescence. Their intellectual functions were normal. Twenty-four-hour video/EEG telemetry recorded during the NCSE showed fluctuating consciousness between overt unresponsiveness and normal awareness. The EEG consisted of long-lasting generalized rhythmic 3-5 Hz sharp or slow waves with a few spikes, lasting several days. Despite the continuous discharges, the patients had relatively subtle clinical episodes of seizures, during which they were sometimes responsive to verbal stimuli. Intravenous antiepileptic drugs (AED) had little effect on the rhythmic EEG. No lesion in their MRIs contributed to NCSE. Ring chromosome 20 was found in 20% of female karyotype in both patients [46,XX,r(20) (p13 q13)/46,XX] but were negative in four healthy siblings. Oral AEDs decreased more than 75% of the overt CPS episodes in both patients at 22 and 26 months of follow-up but had no effect on the natural history of electrical NCSE. The patients' daily activities were minimally affected by the ongoing electrical discharges. These are the first two cases reported of ring chromosome 20 with NCSE in Thailand. Our patients present a rather benign and pharmacologically responsive course probably because of the low percentage of r(20) mosaicism. The electroclinical correlations in our cases raise the possibility that the mechanism of continuous rhythmic waves in this syndrome may be unrelated to epilepsy. Assessing the severity of this syndrome using both clinical seizures and EEG is crucial.

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.

Tourette's syndrome: old syndrome, new insights and new treatment.

Recognized for over 300 years, Tourette's syndrome was originally ascribed as a rare bizarre psychogenic illness. Because of recent advances in research on Tourette's syndrome, this disorder is not only the rarity once thought, but also a common, biological, genetic disorder with a spectrum of neurobehavioral manifestations that wax and wane during its entire natural course. In addition to standard neuroleptics, much progress in Tourette's syndrome research has widened its pharmacotherapy to include alpha2-adrenergic agonists and atypical neuroleptics as well as behavioral modification, adjustments, and different surgical approaches. Despite a myriad of reports, there are still many unresolved facts, which stimulate research into the underlying mechanisms of this complex neuropsychiatric disorder. We anticipate that continued success of research in this area will lead to molecular insights, identification of vulnerable genes, and eventually novel therapies that can target all aspects of this complex disorder.

Hemifacial spasm: results of treatment with low dose botulinum toxin injection.

BACKGROUND: Hemifacial Sapsm (HFS) is a common movement disorder in Thailand. Botulinum toxin type A (BTA) is an effective and safe treatment for this condition. The success of BTA treatment depends on the experience of the clinician. OBJECTIVE: To study the demographic data, efficacy and safety of low dose BTA injection in HFS patients. SETTING: The Spastic and Dystonia Clinic, Department of Rehabilitation Medicine, King Chulalongkorn Memorial Hospital. DESIGN: Open-label, prospective case-series study. PATIENTS: All patients with HFS referred for BTA injection from December 1st, 1995 to November 30th, 2003. METHOD: Sex, age, side of spasm, onset of symptoms before BTA injection, underlying diseases, sites of BTA injection, dose of each BTA treatment, duration of response, efficacy, and side-effects were analyzed. 3-5 units of BOTOX were intramuscularly injected per site to all muscles that had spasm. After injection, a 20-minute cold compression on the first day was followed by 20-minute warm compression with massage at each injection site per day for 14 days. RESULTS: A total of 112 patients with HFS were treated with 874 BTA treatments. There were 71 females (63.4%) and 41 males (36.6%). The mean age was 45 years. 75 patients (67%) were affected on the left side. Mean duration of symptoms was 3.4 years. The sites of injection were orbicularis occuli and orbicularis oris muscles in all 874 treatments (100%). The mean dose of all treatments was 25 units. The mean initial dose was 30.5 units. The mean dose for subsequent injection was 23 units. The mean duration between treatments was 4.7 months. The mean initial duration was 3.5 months. The mean duration for subsequent injection was 4.8 months. The outcomes of treatment assessed at 4 weeks after injection classified as excellent (>80% improvement) were found in 845 treatments (96.7%). Most treatments had no complication (91.9%). Ptosis, facial paresis and double vision were mild and transient, lasting 1-4 weeks. There were no long-term complications of BTA treatment in the present series. CONCLUSION: Low dose BTA injection is an effective treatment for hemifacial spasm patients. There was a longer duration of response in subsequent injections and a lower complication rate in the present study when compared to others.