Oxidative stress can be a final common pathway for AED-induced teratogenesis.
To compare the oxidative stress of women with epilepsy (WWE) and unfavorable pregnancy outcome (fetal malformation or spontaneous abortion - group EM) with that of WWE with normal pregnancy outcome (group ENM) and healthy women with normal pregnancy outcome (group C).
Materials and Methods:
We identified WWE under group EM (n = 43) and group ENM (n = 22) from the Kerala Registry of Epilepsy and Pregnancy (KREP). Group C was constituted of healthy volunteers (N = 20). Oxidative stress was assessed by estimating serum levels of malondialdehyde (MDA) and isoprostane (ISP). The antioxidant profile was evaluated as activity of superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT), total antioxidant status (TAO), and glutathione (GSH) content.
The MDA and ISP levels for group EM (3.46 + 0.82 and 17.77 + 3.0) were higher than that of group ENM (3.07 + 1.02 and 14.0 + 5.3), and both were significantly higher than that of group C (2.42 + 0.51 and 10.77 + 4.1). Their levels of SOD (146.82 + 42.64 vs. 175.81 + 42.61) and GSH (0.98 + 0.98 vs. 1.55 + 1.3) were significantly lower than those of controls. No significant changes were seen in TAO and GR. WWE on polytherapy showed significant increase in MDA when compared to monotherapy group.
WWE (group EM and ENM) had higher oxidative stress and reduced antioxidant activity. The subgroup of WWE with unfavorable pregnancy outcome (group EM) had higher oxidative stress. Excess oxidative stress can be a final common pathway, by which AEDs exert teratogenic effects.
Anti-epileptic drugs; antioxidant; epilepsy; fetal malformation; oxidative stress; teratogenesis
This article is intended to give the reader guidance in evaluating different study designs used in medical research for better scientific quality, reliability and validity of their research. This article explains three main types of study designs with understanding examples. Care and caution with skills and experience needed to design suitable studies and appropriate design coupled with reliable sampling techniques and appropriate statistical analysis, supported by clear objectives with decent communication of the findings, are essential for good research.
Data analysis; study design; trials
Statistical analysis is an essential technique that enables a medical research practitioner to draw meaningful inference from their data analysis. Improper application of study design and data analysis may render insufficient and improper results and conclusion. Converting a medical problem into a statistical hypothesis with appropriate methodological and logical design and then back-translating the statistical results into relevant medical knowledge is a real challenge. This article explains various sampling methods that can be appropriately used in medical research with different scenarios and challenges.
Design; study; sampling
Stigma and resultant psychosocial issues are major hurdles that people with epilepsy confront in their daily life. People with epilepsy, particularly women, living in economically weak countries are often ill equipped to handle the stigma that they experience at multiple levels. This paper offers a systematic review of the research on stigma from sociology and social psychology and details how stigma linked to epilepsy or similar conditions can result in stereotyping, prejudice and discrimination. We also briefly discuss the strategies that are most commonly utilized to mitigate stigma. Neurologists and other health care providers, social workers, support groups and policy makers working with epilepsy need to have a deep understanding of the social and cultural perceptions of epilepsy and the related stigma. It is necessary that societies establish unique determinants of stigma and set up appropriate strategies to mitigate stigma and facilitate the complete inclusion of people with epilepsy as well as mitigating any existing discrimination.
Epilepsy; gender issues; quality of life; stigma; treatment gap
To assess the knowledge of obstetricians about concerns of women with epilepsy.
Materials and Methods:
We surveyed 97 obstetricians (teaching hospitals—43, private hospitals—32, and community health centers–21) using knowledge of women's issues and epilepsy (KOWIE) questionnaire II with additional questions.
The mean duration of practice of the surveyed obstetricians was 12.4 ± 10.7 years and 94% were female doctors. Most of them were well informed about the teratogenic effects of AEDs (91%), need to continue antiepileptic drugs (AEDs) during pregnancy (95%), and the role of folic acid and vitamin K during pregnancy (95%). They agreed AEDs decrease the efficacy of oral contraception and it was safe for the woman to breast-feed the baby while on AEDs. Only 1/3rd of them knew that steroid hormones could alter seizure threshold or that AEDs could predispose to osteomalacia. Fewer doctors knew that WWE could have increased sexual dysfunction (29.9%) or infertility (26.8%). The knowledge did not vary according to years of practice or practice settings.
Obstetricians were well informed about the fetal complications of antenatal AED exposure, but were under informed of other complications such as osteomalacia, sexual dysfunction, and infertility.
Knowledge; obstetricians; survey; women with epilepsy
The cerebrospinal fluid hypovolemia syndrome (CHS) is an under recognized cause of headache. This study was designed to highlight the clinico-radiological and cerebrospinal fluid (CSF) picture of CHS and their long-term outcome from a tertiary referral center.
Materials and Methods:
The CHS was diagnosed on the basis of the criteria proposed by Chung et al. Cases with CSF rhinorrhoea or other CSF leak or head trauma were excluded from the study.
The study included eight consecutive cases of CHS diagnosed over the past 7 years from 2001. The mean age at diagnosis was 40.7 years (range, 34-56 years) and male-to-female ratio was 1:3. All patients presented with orthostatic headache of subacute onset and normal neurological examination. Magnetic resonance imaging studies of all patients showed hyperintensity of pachymeninges in T2W sequences, venous distension sign, and diffuse pachymeningeal gadolinium enhancement. The descent of the brainstem and subdural effusion were noted in two each (25%). CSF study (n = 5) showed low opening pressure in three (60%), and mild pleocytosis with elevated protein in two each (40%). The mean time to complete recovery with conservative treatment alone was 25.6 days. All radiological signs disappeared with clinical improvement in three patients where follow-up imaging was done. On mean follow-up period of 3.6 years, all were asymptomatic without any recurrence of CHS.
CHS can resolve completely with conservative management and intervention with subdural blood patch or surgical repair would be required only if symptoms persist for more than 1 month.
Headache; spontaneous intracranial hypotension; venous distension sign
Comprehensive instruments to evaluate the child rearing knowledge and practice are not readily available for clinical research.
Materials and Methods:
We have designed in two phases a new instrument to evaluate the child rearing knowledge and practice under the four major domains of child rearing. Twenty-five subject experts from the field of Paediatrics, Obstetrics, Neurology and Nursing elicited the content validity of the instrument. The test retest reliability was evaluated by 25 young mothers who completed the CRKS at an interval of two weeks.
The Content Validity Ratio (CVR) of individual items ranged between 0.6 to 1. The reliability was tested for the 20 individual items of the CRKS using Kappa coefficient. The measurement of agreement Kappa ranged from 0.51 to 1. The total knowledge scores and sub scores data were analysed for correlation using Pearson’s correlation coefficient. A significant Pearson’s correlation indicated that the total scores were consistent over time (r = 0.89). The sub scores on feeding (6 items), Growth and development (4 items), protection (7 items), and infant stimulation (3 items) were found to have reliability of 0.91, 0.76, 0.84, and 0.89 respectively using Pearson’s correlation.
The instrument is found to be valid and reliable and can be used to measure child rearing knowledge and practice in early infancy.
Child rearing knowledge; child rearing practice scale; reliability and validity
To describe the clinical, radiological, and cerebrovascular fluid (CSF) findings and the outcome of microbiologically or histopathologically proven fungal infections of the central nervous system (CNS) in HIV-negative patients.
Methodology and Results:
We identified definite cases of CNS mycosis by screening the medical records of our institute for the period 2000–2008. The clinical and imaging details and the outcome were abstracted from the medical records and entered in a structured proforma. There were 12 patients with CNS mycosis (i.e., 2.7% of all CNS infections treated in this hospital); six (50%) had cryptococcal infection, three (25%) had mucormycosis, and two had unclassified fungal infection. Four (33%) of them had diabetes as a predisposing factor. The common presentations were meningoencephalitis (58%) and polycranial neuritis (41%). Magnetic resonance imaging revealed hydrocephalus in 41% and meningeal enhancement in 25%, as well as some unusual findings such as subdural hematoma in the bulbocervical region, carpeting lesion of the base of the skull, and enhancing lesion in the cerebellopontine angle. The CSF showed pleocytosis (66%), hypoglycorrhachia (83%), and elevated protein levels (100%). The diagnosis was confirmed by meningocortical biopsy (in three cases), paranasal sinus biopsy (in four cases), CSF culture (in three cases), India ink preparation (in four cases), or by cryptococcal polysaccharide antigen test (in three cases). Out of the ten patients for whom follow-up details were available, six patients recovered with antifungal medications (amphotericin B, 1 mg/kg/day for the minimum period of 6 weeks) and/or surgical treatment. Four patients expired (only one of them had received antifungal therapy).
Most patients with CNS mycosis recover with appropriate therapy, but the diagnosis and management of these rare infections remains a challenge to clinicians.
Amphotericin; central nervous system mycosis; outcome
Status epilepticus (SE) is a medical emergency associated with significant morbidity and mortality. SE is defined as a continuous seizure lasting more than 30 min, or two or more seizures without full recovery of consciousness between any of them. Based on recent understanding of the pathophysiology, it is now considered that any seizure that lasts more than 5 min probably needs to be treated as SE. GABAergic mechanisms play a crucial role in terminating seizures. When the seizure persists, GABA-mediated mechanisms become ineffective and several other putative mechanisms of seizure suppression have been recognized. Early treatment of SE with benzodiazepines, followed if necessary by fosphenytoin administration, is the most widely followed strategy. About a third of patients with SE may have persistent seizures refractory to the first-line medications. They require aggressive management with second-line medications such as barbiturates, propofol, or other agents. In developing countries where facilities for assisted ventilation are not readily available, it may be helpful to use nonsedating antiepileptic drugs (such as sodium valproate, levetiracetam, or topiramate) at this stage. It is important to recognize SE and institute treatment as early as possible in order to avoid a refractory state. It is equally important to attend to the general condition of the patient and to ensure that the patient is hemodynamically stable. This article reviews current knowledge regarding the management of convulsive SE in adults.
Anticonvulsants; barbiturates; lorazepam; midazolam; phenytoin; propofol; refractory status epilepticus; status epilepticus
Acquired resistance to antibiotics and other chemotherapeutic agents is a major problem in the practice of neurology and other branches of medicine. There are several mechanisms by which drug resistance is acquired. Multidrug transporters are important glycoproteins located in the cell membrane that actively transport small lipophilic molecules from one side of the cell membrane to the other, most often from the inside to the outside of a cell. They have important protective role yet may prove inconvenient in chemotherapy. In epilepsy and other disorders this mechanism augments the elimination of drugs from their target cells and leads to drug resistance. In this review, we have discussed the biochemical characteristics of multidrug transporters and the mechanisms by which these membrane bound proteins transport their target molecules from one side to the other side of the cell membrane. We have also briefly discussed the application of this knowledge in the understanding of drug resistance in various clinical situations with particular reference to neurological disorders. These proteins located in the placenta have important role in preventing the transplacental movement of drugs in to the fetus which may result in congenital malformations or other defects. The molecular genetic mechanisms that govern the expression of these important proteins are discussed briefly. The potential scope to develop targeted chemotherapeutic agents is also discussed.
Drug resistant epilepsy; multidrug resistance; multidrug resistance protein; P-glycoprotein; teratogenic effect; transport proteins