Sunil K. Narayan

CARDIOVASCULAR AUTONOMIC REGULATION IN SUBJECTS WITH NORMAL BLOOD PRESSURE, HIGH–NORMAL BLOOD PRESSURE and RECENT-ONSET HYPERTENSION

1. In the present study, we tested the hypothesis that heart rate variability (HRV) is reduced in recent‐onset hypertension and that pressor responses to standard autonomic reflex tests are not any different in hypertensives compared with normotensives. We also hypothesized that subjects with high–normal blood pressure (BP) would be distinguishable from normotensives on the basis of short‐term HRV indices.

Influence of CYP2C9 and CYP2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients

ObjectiveCytochrome P450 2C9 and 2C19 (CYP2C9 and CYP2C19, respectively) genetic polymorphisms play an important role in phenytoin (PHT) metabolism. We have evaluated whether these genetic polymorphisms have an effect on PHT-induced neurological toxicity in Tamilian (ethnic group native to southern India) patients with epilepsy.MethodsWe studied 292 Tamilian patients who were taking PHT for the treatment of various epileptic seizures. PHT toxicity was defined on the basis of neurological signs of toxicity and further sub-classified into mild, moderate, and severe toxicity based on clinical severity. Genomic DNA was extracted from peripheral leukocytes and genotyped for CYP2C9*2, *3 and CYP2C19*2, *3 by PCR-restriction fragment length polymorphism analysis.ResultsOf the 292 patients in the patient cohort, 58 were clinically diagnosed to have PHT toxicity. When risk ratios were calculated for each mutant CYP2C9 genotype separately, the adjusted odds ratio for CYP2C9*1/*3 was found to be 15.3 (95% confidence interval 5.8–40.3, P < 0.0001) for the cases compared to controls. When the four single nucleotide polymorphisms of CYP2C9 and CYP2C19 were analyzed using a haplotype approach, significant difference in the distribution of the C-C-G-G haplotype was observed between the cases and controls.ConclusionOur results show that CYP2C9 genetic polymorphisms (particularly the *3 allele) were associated with high risk of epileptic patients developing PHT-induced neurological toxicity.

Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India

The authors report an Indian adult female patient with a history of generalized tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity on therapeutic dosage of this antiepileptic drug. Administration of 300 mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33 microg/ml. The PCR-RFLP analysis revealed a homozygosity involving CYP2C9*3*3. This mutation results in a marked decrease in the enzymatic activity (CYP2C9) and leads to a decreased clearance of the drug which can lead to severe acute and chronic toxicity. On switching the antiepileptic therapy from DPH to sodium valproate, there was reversal of both.

Evaluation of an IgG-ELISA strategy using Taenia solium metacestode somatic and excretory-secretory antigens for diagnosis of neurocysticercosis revealing biological stage of the larvae.

Diagnosis of neurocysticercosis (NCC) is complicated because of the variability in clinical presentations and course of the disease where viability of parasite is a major determinant. The present study describes evaluation of ELISAs using Taenia solium metacestode somatic and excretory-secretory (ES) antigens for detection of anti-T. solium metacestode IgG antibodies in serum and cerebrospinal fluid (CSF). And results of the ELISAs in cases with a definitive diagnosis of NCC are correlated with the biological stages of the parasite such as live vesicular or degenerated stage. The sensitivity of the IgG-ELISA using ES antigen is observed to be much higher in serum (88.2%) than in CSF (64.28%) although it is only marginally higher in serum (76.4%) than in CSF (75%) when somatic antigen is used in the ELISA. Whereas, the specificities of the ELISA using either somatic or ES antigen for detection of IgG antibodies in serum (97.97%; 96.96%) and CSF (96.42%; 97.61%) are comparable. A strong association is observed between live stage of the parasite and detection of antibodies in sera and CSF from more number of NCC patients by ELISA using ES antigens. Similarly, detection of antibodies by ELISA using somatic antigens could be associated with the dead or degenerated stage of the parasite in brain. The IgG-ELISA strategy developed in the present study opens up an avenue for diagnosis of NCC in hospitals or in population prevalence studies. The use of crude extracts of ES proteins might improve the serodiagnosis of the cases of NCC carrying live vesicular stage of the parasite larvae.

CNS demyelination due to hypocupremia in Wilson's disease from overzealous treatment

Untreated Wilson’s disease in advanced stage is associated with high neurological morbidity, and effective treatment with chelating agents and zinc salts has shown to prevent the development of or reverse neurological symptoms. [1] However an overzealous treatment with zinc over a prolonged period can have its own dangers.

Plasma homocysteine levels in depression and schizophrenia in South Indian Tamilian population

Context: Hyperhomocysteinemia has been associated with psychiatric diseases in non-Indian populations. Objectives: We aimed to determine if total plasma Homocysteine (Hcys) is associated with schizophrenia or depression in South Indian Tamil patients and if so, to correlate their severity and phenomenology to Hcys levels. Settings and Design: 40 patients each with schizophrenia and depression and 40 healthy controls were recruited from the psychiatry department of a quaternary referral centre. Association between Hcys and psychiatric disorders was determined using a Case- control design. Hcys levels were correlated with age, gender and severity and duration of the disease by appropriate statistical methods using SPSS17. Materials and Methods: Schizophrenia and depression were defined using ICD10 DCR version. Severity of depression was assessed by Hamilton Depression Rating Scale and that of schizophrenia using Positive and Negative Schizophrenia scales (PANSS). Hcys levels were determined using automated chemiluminiscence immunoassay (74-76). Statistical Analysis: Differences between the mean values of plasma homocysteine levels among schizophrenia, depression and control groups were compared using analysis of variants. The association between the severity and duration of schizophrenia and depression and the plasma homocysteine levels were determine using Pearson correlation. Conclusions: In Tamilian population, schizophrenia and depression are associated with total plasma Hcys levels which correlated with the duration and severity of psychosis.

Influence of CYP2C9 genetic polymorphism and undernourishment on plasma-free phenytoin concentrations in epileptic patients.

The objective of this study was to study the effect of CYP2C9 genetic polymorphism and undernourishment on free phenytoin concentrations in epileptic patients. The study was done in 70 patients who were taking phenytoin therapy for the treatment of epileptic seizures. Genotyping of CYP2C9 (*2 and *3) was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Bound and free plasma phenytoin was separated using equilibrium dialysis technique. Total and free phenytoin concentrations were measured by the reverse-phase high-performance liquid chromatography method. Patients were broadly classified into well-nourished and undernourished and further subclassified by CYP2C9 genotypes. In well-nourished groups (G1 to G3 group), free phenytoin concentrations were significantly higher in the heterozygous poor metabolizer of CYP2C9 genotype (G2) group (3.1 ± 0.62 μg/mL) and homozygous poor metabolizer of CYP2C9 genotype (G3) group (4.3 ± 1.76 μg/mL) when compared with patients with the wild-type CYP2C9 (G1) group (1.1 ± 0.72 μg/mL). Similarly, in undernourished patient groups (G4-G6 group), free phenytoin concentrations were significantly higher in the wild-type CYP2C9 (G4) group (2.5 ± 0.52 μg/mL), heterozygous poor metabolizer of CYP2C9 genotype (G5) group (4.3 ± 1.76 μg/mL), and homozygous poor metabolizer of CYP2C9 genotype (G6) group (8.2 ± 1.08 μg/mL) when compared with well-nourished patients with the wild-type CYP2C9 (G1) group (1.1 ± 0.72 μg/mL). The percentage increase in free phenytoin concentration by undernourishment, CYP2C9 allelic variants, and undernourishment cum CYP2C9 allelic variants were 127%, 290%, and 472%, respectively, compared with well-nourished patients with the wild-type CYP2C9 genotype (G1) group. The contribution of undernourishment and genetic factors (CYP2C9 allelic variant) for developing phenytoin toxicity was calculated to have an odds ratio of 37.3 (P < 0.0001). Undernourishment and variant CYP2C9 alleles elevate free phenytoin concentrations individually and in combination show additive effects.

Anthrax meningoencephalitis — Declining trends in an uncommon but catastrophic CNS infection in rural Tamil Nadu, South India

INTRODUCTION Anthrax, a cattle-born zoonosis has been a serious infectious disease and its meningoencephalitic form remains a rapidly fatal illness even now. AIM The aim of this paper is to evaluate the incidence and clinical profile of anthrax meningoencephalitis admitted to a teaching hospital predominantly serving a rural population in South India. MATERIALS AND METHODS We made a systematic study of the case records of patients with microbiologically confirmed diagnosis of anthrax meningoencephalitis admitted over a 20-year period. We searched the internet and office records for the anthrax outbreaks and the preventive strategies in place in India. RESULTS The admissions occurred in two clusters, four during 1992-1994 and six in 1998-2000; with no further detection unto August 2008. All patients were adult males with agriculture related occupation. Three of the 10 patients had no evidence of primary focus of infection. Majority were in coma at admission and had documented evidence of septicemia. CSF was haemorrhagic and death was the uniform outcome despite high dose intravenous penicillin G; maximum duration of hospital survival being 48 h. COMMENT Anthrax is a rare, but catastrophic cause of meningoencephalitis. Improvement in education and life styles as well as livestock vaccination in rural areas appear to have effectively decreased the incidence of this dreaded acute zoonosis in the South Indian states of Tamilnadu and Puducherry.

Neuroretinitis, a great mimicker

Neuroretinitis is a less-known clinical entity, which can be funduscopically confused with papillitis or papilledema and with hypertensive, renal and infiltrative retinopathies as well as with retinal vein occlusion or anterior ischemic optic neuropathy. Report: Two young patients presented with sudden onset of blurring of vision. Ophthalmic evaluation revealed a characteristic picture of neuroretinitis. Detailed study of the cases failed to indicate any specific etiology, thereby suggesting the diagnosis of idiopathic neuroretinitis. Although funduscopy showed marked inflammatory changes in the retina and optic nerve head, the recovery following medical treatment was remarkable. Comment: Familiarity with the fundus picture and awareness of the specific causes of neuroretinitis among neurologists and physicians may enable a prompt clinical diagnosis, avoidance of expensive brain imaging studies and early referral for appropriate and effective therapy. A brief review of the literature is presented suggesting a need for further studies to establish specific environmentally determined etiological factors such as infections and the effectiveness of the current modalities of treatment.

Low luminance/eyes closed and monochromatic stimulations reduce variability of flash visual evoked potential latency

Context: Visual evoked potentials are useful in investigating the physiology and pathophysiology of the human visual system. Flash visual evoked potential (FVEP), though technically easier, has less clinical utility because it shows great variations in both latency and amplitude for normal subjects. Aim: To study the effect of eye closure, low luminance, and monochromatic stimulation on the variability of FVEPs. Subjects and Methods: Subjects in self-reported good health in the age group of 18-30 years were divided into three groups. All participants underwent FVEP recording with eyes open and with white light at 0.6 J luminance (standard technique). Next recording was done in group 1 with closed eyes, group 2 with 1.2 and 20 J luminance, and group 3 with red and blue lights, while keeping all the other parameters constant. Two trials were given for each eye, for each technique. The same procedure was repeated at the same clock time on the following day. Statistical Analysis: Variation in FVEP latencies between the individuals (interindividual variability) and the variations within the same individual for four trials (intraindividual variability) were assessed using coefficient of variance (COV). The technique with lower COV was considered the better method. Results: Recording done with closed eyes, 0.6 J luminance, and monochromatic light (blue > red) showed lower interindividual and intraindividual variability in P2 and N2 as compared to standard techniques. Conclusions: Low luminance flash stimulations and monochromatic light will reduce FVEP latency variability and may be clinically useful modifications of FVEP recording technique.