Search

Objective: Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 (CYP2C9*2/*3) and vitamin K epoxide reductase subunit 1 (VKORC1) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST. Methods: The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1, CYP2C9*2, and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis. Results: INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23–13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13–0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06–0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05–0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19–26.06, P = 0.02). Conclusions: Variant genotypes of VKORC1, CYP2C9*2, and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention.

Epilepsia partialis continua (EPC) is a rare form of status epilepticus and often refractory to antiepileptic drugs (AEDs). Persistent seizure activity may increase pro-inflammatory biomarkers locally, which may respond to adjunctive corticosteroid treatment, especially in central nervous system (CNS) infections. We report four children with refractory EPC and the effect of adjunctive corticosteroid in controlling EPC. The duration of EPC ranged between 3 days and 7 months. One patient had secondary generalized convulsive status epilepticus. Cranial computed tomography/magnetic resonance imaging was abnormal in three out of four patients; revealing old infarction in one, tuberculoma in one, and neurocysticercosis in one. Electroencephalography revealed spike and sharp wave discharges on the corresponding cerebral hemisphere. The EPC was refractory to 2-6 AEDs. Following corticosteroid treatment, EPC remitted in two patients with CNS infection, and those with infarction and cryptogenic EPC converted to discrete seizures. In AED-resistant EPC, a short course of corticosteroid may be helpful.

Status epilepticus (SE) is an emergency neurological problem, more common in the developing countries due to high incidence of infection, stroke and head injury. The protocol for management of SE is intravenous benzodiazepine, followed by phenytoin, valproate (VPA) and phenobarbitone and if uncontrolled general anesthesia (GA). World Federation of Neurology recommends special guidelines for resource poor countries. Use of GA results in hypotension and respiratory depression needing intensive care management. There is a paucity of intensive care facilities hence the recommended antiepileptic drugs (AEDs) which have inherent toxicity of hypotension and respiratory failure cannot be given safely. Under these situations AEDs such as VPA, levetiracetam and lacosamide may be evaluated in SE because of cardiovascular and respiratory safety profile. In this review, the limitations of existing guidelines in the developing countries have been discussed and a way forward has been suggested.

Oral anticoagulation (OAC) is difficult to maintain in therapeutic range and their efficacy may be influenced by number of clinical and genetic variables. The objective of the study is to evaluate the role of VKORC1 polymorphism and correlate with stability of anticoagulation. It is a hospital based study. Patients on OAC were included during 2013-2016. The patients received OAC for cardioembolic stroke, cortical venous sinus thrombosis (CVST) and prevention of deep vein thrombosis (DVT). Demographic, clinical and neurological findings were recorded. Stability of OAC was determined by percentage of international normalized ratio (INR) values in therapeutic range (PINR). PINR >65% were defined as stable and

Microstructural changes of the trigeminal nerve in trigeminal neuralgia due to neurovascular compression have been reported by using diffusion tensor imaging. Other aetiologies such as primary demyelinating lesions, brain stem infarction and nerve root infiltration by tumour affecting the trigeminal pathway may also present as trigeminal neuralgia. The aim of this study was to evaluate the microstructural tissue abnormalities in the trigeminal nerve in symptomatic trigeminal neuralgia not related to neurovascular compression using diffusion tensor imaging. Mean values of the quantitative diffusion parameters of trigeminal nerve, fractional anisotropy and apparent diffusion coefficient, were measured in a group of four symptomatic trigeminal neuralgia patients without neurovascular compression who showed focal non-enhancing T2-hyperintense lesions in the pontine trigeminal pathway. These diffusion parameters were compared between the affected and unaffected sides in the same patient and with four age-matched healthy controls. Cranial magnetic resonance imaging revealed hyperintense lesions in the dorsolateral part of the pons along the central trigeminal pathway on T2-fluid-attenuated inversion recovery sequences. The mean fractional anisotropy value on the affected side was significantly decreased (P = 0.001) compared to the unaffected side and healthy controls. Similarly, the mean apparent diffusion coefficient value was significantly higher (P = 0.001) on the affected side compared to the unaffected side and healthy controls. The cause of trigeminal neuralgia in our patients was abnormal pontine lesions affecting the central trigeminal pathway. The diffusion tensor imaging results suggest that microstructural tissue abnormalities of the trigeminal nerve also exist even in non-neurovascular compression-related trigeminal neuralgia. [ABSTRACT FROM AUTHOR]