Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population.

OBJECTIVE: This study aimed to describe the genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions (PHT-induced cADRs) in Thai patients. METHOD: A retrospective case-control study was conducted among 88 PHT- cADRs (25 SJS/TEN, 37 DRESS/DIHS and 26 MPE) compared to 70 PHT-tolerant controls during 2008-2017. Genotyping was performed by Taqman RT-PCR (EPHX1 337 T > C, EPHX1 416A > G and CYP2C9*3), pyrosequencing (UGT1A1*28, UGT1A1*6) and polymerase chain reaction-sequence-specific oligonucleotide probe (HLA-B). Chi-squared test and binary logistic regression were used to identify factors associated with PHT-cADRs. RESULTS: Multivariate analysis showed that HLA-B*46:01 was significantly associated with all PHT-induced cADRs (OR 2.341; 95% CI, 1.078-5.084; P = .032). Age of ≥60 years showed a significant association with PHT-induced SJS/TEN (OR 3.600; 95% CI, 1.214-10.672; P = .021). CYP2C9*3 was almost reaching statistically associated with an increased risk of PHT-induced SJS/TEN (OR 4.800; 95% CI, 0.960-23.990; P = .056). While HLA-B*56:02/04 was found to have a significant association with PHT-induced DRESS/DIHS (OR 29.312; 95% CI, 1.213-707.994; P = .038). Moreover, female gender and HLA-B*40:01 were associated with an increased risk of PHT-induced MPE at OR 5.734; 95% CI, 0.910-58.351; P = .042 and OR 3.647; 95% CI, 1.193-11.147; P = .023, respectively. CONCLUSION: Both clinical (advanced age, female gender) and genetic factors (HLA-B*46:01, CYP2C9*3, HLA-B*56:02/04 and HLA-B*40:01) contributed to the risk of PHT-induced cADRs. Further studies with larger sample size may be warranted to confirm these findings and also the influence of EPHX1 gene.

Prevalence of psychiatric disorders in Thai patients with epilepsy.

BACKGROUND: Many studies have shown that the prevalence of psychiatric disorders in patients with epilepsy (PWE) appears higher than that in general population. However, most epidemiological studies regarding psychiatric comorbidities among PWE were conducted in Western countries. This work aimed to determine the prevalence of psychiatric disorders in Thai PWE, including potential variables that could be associated with psychiatric disorders. METHODS: A cross-sectional study was conducted at Ramathibodi Hospital. A total of 170 patients (aged 18 years or older) diagnosed as having epilepsy by a neurologist were recruited at the outpatient neurology clinic. Demographic and clinical characteristics were collected. Participants were evaluated for any psychiatric disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, using a structured diagnostic interview. The prevalence of psychiatric disorders was determined. The associations between potential variables and the presence of psychiatric disorders in PWE were analyzed using chi-square or Fisher's exact tests, t-test, and logistic regression. RESULTS: Among 170 patients, 43 (25.3%) fulfilled diagnostic criteria for one or more psychiatric disorders. The prevalence of depressive disorders was shown to be highest at 17.1%, followed by psychotic disorders (8.2%), bipolar disorder (7.1%), anxiety disorders (5.3%), and obsessive-compulsive disorder (OCD) (2.9%). Electroencephalogram (EEG) abnormalities in the temporal lobe was found to be a significant predictor of having psychiatric disorders in PWE (adjusted odds ratio (OR): 4.01, 95% confidence interval (CI): 1.47-10.92, P-value = 0.007). CONCLUSIONS: The prevalence of psychiatric disorders among Thai PWE was higher than that in general population. Screening for psychiatric disorders in PWE is recommended, especially among those who have EEG abnormalities in the temporal lobe.

Deep Brain Stimulation of Anterior Thalamic Nuclei for Intractable Epilepsy in Thailand: Case Report

Neurostimulation can be an alternative treatment for medically intractable epilepsy, especially when the resective surgery could not be performed. The author reported a case of 19-year-old, right-handed male patient who had a history of intractable epilepsy for 11 years after post viral encephalitis associated with status epilepticus. Following the failure of antiepileptic medications and then resective surgery, anterior thalamic deep brain stimulation (DBS) was performed. Indirect targeting of anterior thalamic nuclei could not be used because of asymmetric brain shift from prior multilobar resections. Direct targeting of anterior thalamic nuclei from MRI T1 sequence, Short Tau Inversion Recovery (STIR) sequence combined neurophysiological mapping by microelectrode recording were used as a technique for implantation of DBS electrodes. The stimulation was turned on with 145 Hz, pulse width 90 microseconds, 5 volts with cycling mode 1 minute "on" and 5 minutes "0ff". The antiepileptic medications continued the same as pre-operative state. Sixty percent seizure reduction was achieved in 24 months after surgery. There were no side effects of DBS during the follow-up period. Anterior thalamic DBS can be performed safely with satisfactory seizure outcomes. Direct targeting of anterior thalamic nuclei combination with microelectrode recording can be very helpful, especially when asymmetric basal ganglion structures were detected.

Spinocerebellar Ataxia type 17 presenting with progressive myoclonic epilepsy.

•SCA17 should be included in the differential diagnoses of PMEs.•SCA17 is characterized by cerebellar features, myoclonic epilepsy, cognitive decline, psychiatric features, and chorea.•Subtle clinical signs like chorea can provide additional diagnostic clues to SCA17(HDL4), a Huntington disease phenocopy.

Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand.

Objective: This study aimed to investigate the clinical impact of HLA-B*15:02 pharmacogenomics (PGx) testing before carbamazepine (CBZ)/oxcarbazepine (OXC) prescriptions and to determine whether this PGx testing was associated with the reduction of CBZ/OXC-induced cutaneous adverse drug reactions (CADRs) in Thailand. Methods: This retrospective observational cohort study was conducted by obtaining relevant HLA-B*15:02 PGx-testing and clinical data from electronic medical records during 2011-2020. 384 patient data were included in this study to investigate the clinical decision on CBZ/OXC usage before and after the HLA-B*15:02 PGx testing, and 1,539 patient data were included in this study to demonstrate the incidence of CBZ/OXC-induced SCARs and SJS between HLA-B*15:02 tested and non-tested patients. To analyze and summarize the results, descriptive statistics were employed, and Fisher exact test was used to compare the clinical difference between the HLA-B*15:02 positive and negative groups and to compare the differences of SCARs incidence. Results: 384 patients were included in this study as per the inclusion criteria. Of these, 70 patients carried HLA-B*15:02, of which 63 and 65 patients were not prescribed with CBZ/OXC before and after the availability of genotyping results, respectively. In the remaining HLA-B*15:02 non-carriers, 48, and 189 patients were prescribed CBZ/OXC before and after genotyping results were available, respectively. The findings of this study showed that the incidence of SCARs of CBZ/OXC was significantly lower (p < 0.001) in the HLA-B*15:02 screening arm than in the non-screening arm. Conclusion: HLA-B pharmacogenetics testing influenced the selection of appropriate AEDs. The presence of mild rash in the HLA-B*15:02 negative group indicates that other genetic biomarker (HLA-A*31:01) and/or non-genetic variables are involved in CBZ/OXC-induced CADRs, emphasizing that CBZ/OXC prescriptions necessitate CADR monitoring. The hospital policy and clinical decision support (CDS) alert system is essential to overcome the barriers associated with the utilization of PGx guidelines into clinical practice.

Garbled and Incoherent Text Messages Are a Sign of Acute Ischemic Stroke: A New Sign of Aphasia in the Era of Chat Applications.

We report a 68-year-old female was diagnosed acute ischemic stroke with an interesting clinical presentation. She was unable to send the messages in chat application normally and accurately. Neurological examination revealed global aphasia without weakness. Computed tomography angiography (CTA) showed the occlusion of the inferior branch of the left M2 of middle cerebral artery (MCA) but showed a good collateral score. Intravenous fibrinolysis and mechanical thrombectomy were not indicated. The patient showed spontaneous clinical improvement and almost fully recovered by the day of hospital discharge. Currently, chat applications have been widely adopted for communication and have replaced direct or telephone conversations in daily life. Dystextia and dystypia may serve as modern sign of aphasia on text conversation.