Reduced brain volumes in children of women with epilepsy: A neuropsychological and voxel based morphometric analysis in pre-adolescent children.

BACKGROUND AND PURPOSE: Children of Women with Epilepsy with antenatal exposure to antiepileptic drugs (CAED) have reduced neuropsychological functions. We aimed to explore the anatomical basis for this impairment by comparing the brain volumes of CAED with that of matched healthy children without antenatal AED exposure (COAED). MATERIALS AND METHODS: CAED aged 8-12 years were recruited from the Kerala Registry of epilepsy and pregnancy that prospectively follows up children of women with epilepsy and COAED from children attending the imaging department for minor illnesses. Maternal clinical details and the neuropsychological data including IQ of CAED and COAED were obtained. Total intracranial volume (TBV), grey matter volume (GMV), white matter volume (WMV) and volumes of deep grey matter were measured by Voxel Based Morphometry. RESULTS: We studied 30 CAED (mean age 10.8+1.11 years) and 35 COAED (mean age 10.64+1.26). The antenatal AED exposure for the CAED was monotherapy for 8 children and polytherapy for 22 children. The CAED had significantly lower (P<0.001) IQ (77.5+13.8), TBV(1259.55±169.85mL) and GMV (672.51±85.42 mL) compared to the IQ (87.0+13.5), TBV(1405.37±161mL) and GMV (745.427±86.69 mL) of COAED. CAED had lower volumes for Lt Inferior Triangular Gyrus, and hippocampi on both sides, when compared to COAED. Group analysis CAED showed less GMV (P<0.05) for left inferior and middle frontal gyri relative to COAED. CONCLUSIONS: These observations point towards an anatomical basis of lower GMV for the lower neuropsychological functions in children with antenatal AED exposure.

Maternal and obstetric outcome of women with epilepsy.

UNLABELLED: Medical professionals and public are concerned about the complications of pregnancy and delivery in women with epilepsy (WWE). PURPOSE: Our aim was to prospectively ascertain occurrence of these complications in a cohort of WWE enrolled in a pregnancy registry. METHODS: All complications during pregnancy, delivery and first 48 h of postpartum period were recorded according to the registry protocol. This data were compared with similar statistics (for women without epilepsy) from a large teaching hospital. RESULTS: Between April 1998 and March 2005, there were 643 completed pregnancies in this registry. (Mean age 25.7+/-4.43 years; generalized epilepsy 46%; localization related epilepsy 54%; primigravida 53%.) Their complications are compared with those of 18,272 pregnancies managed in the teaching hospital (in parentheses). Spontaneous abortions 4.2% (2.38%); medical termination of pregnancies 2.64% (7.71%); anemia 0.62% (0.22%); gestational diabetes 1.56% (3.09%); pregnancy induced hypertension 3.89% (6.45%); antepartum hemorrhage 0.93% (1.64%); preterm labor 1.87% (6.12%); obstructed labor 0.62% (3%); cesarean section 33.4% (29.5%); assisted delivery 2.8% (2.68%); postpartum hemorrhage 0.31% (0.64%); peripartum seizures 1.4% (0.04%); intrauterine death 1.56% (2.2%); fibroid uterus or ovarian cyst 2.33% (0.53%); other medical illness 2.5% (2.15%); TORCH infection 0.31% (0.01%); birth weight <2.0 kg 4.19% (7.66%). CONCLUSIONS: There was no significant increase in the risk of complications of pregnancy or delivery except for spontaneous abortions, anemia, ovarian cyst, fibroid uterus, and seizures in the peripartum period which were more frequent in WWE. Frequency of cesarean section is not increased in WWE. There is no undue risk to pregnancy and childbirth in most WWE.

Proposed diagnostic criteria for intracranial infectious aneurysms.

BACKGROUND: We propose a set of criteria for diagnosis of intracranial infectious aneurysm (IA). The proposed diagnostic criteria contain a mandatory criterion (demonstration of intracranial aneurysm by neuroimaging) and 12 supportive criteria drawn from three domains. Domain A encompasses infection, such as infective endocarditis, meningitis, cavernous sinus thrombophlebitis or orbital cellulitis. Domain B encompasses angiographic features of the aneurysm, such as multiplicity, distal location, fusiform shape, change in size or appearance of new aneurysm at follow-up angiogram. Domain C encompasses other features, such as age <45 years, recent history of fever, lumbar puncture or cerebral haemorrhage. Each criterion is given 1 point and the sum under each domain (A(sum), B(sum) and C(sum)) and total score are calculated. METHODS: We evaluated these criteria in 25 patients with confirmed IA and in another 111 consecutive patients with non-infectious aneurysm. The sensitivity, specificity and receiver operator characteristic (ROC) curves were calculated for these cohorts. RESULTS: The highest ROC was for total score (0.997). A total score of 3 had high sensitivity (96%) and specificity (100%), as well as a positive predictive value of 100% and negative predictive value of 99.4%. A total score of 2 had high sensitivity (100%) but low specificity (87.4%). Other combinations had lower ROC areas, sensitivities and specificities. CONCLUSION: Diagnosis of IA would be clinically compelling if three or more of the proposed supportive criteria are satisfied, or clinically probable if two proposed supportive criteria are satisfied apart from the mandatory criteria.

Tuberculous aneurysm of extracranial carotid artery.

Incidence of extracranial carotid aneurysm is rare and represents a challenge to treatment strategy. Two patients presented to us a couple of years apart with pulsatile neck swellings. We propose that the extracranial carotid artery pseudoaneurysm was as a result of direct extension from tuberculous lymphadenitis and discuss the management of these patients.

Accidents and injuries in people with epilepsy attending a tertiary care center in India.

People with epilepsy have a higher risk of accidents and injuries when compared to others in the community. Seizure frequency and other characteristics of epilepsy and its treatment are known to influence this risk. The risk of accidental injury to people with epilepsy may vary in different geographical areas, according to their life style, leisure activities and other pursuits. The objective was to ascertain the accidents and injuries experienced by a cohort of people with epilepsy in India, and to ascertain any possible predictors. The study was carried out in the Epilepsy Clinic of Sree Chitra Tirunal Institute for Medical Sciences and Technology between January and June 2007. Using a structured questionnaire, we interviewed all consenting adults attending this tertiary epilepsy center who had had active epilepsy for one or more years. Two hundred and fifty five patients completed the study. The diagnoses included localization-related epilepsy for 62.6% of the patients and generalized epilepsy for the remainder. During the 12 months prior to the interview, 44.8% had had at least one injury; 7.8% had sustained an accident. Road traffic accidents (3.1%), burns (2.5%), electric shocks (0.8%) and near drowning (0.4%) were the commonly reported accidents. Age, sex, type of epilepsy and type of medication had no significant association with the occurrence of injuries or accidents. However, we found that a quarter of the people with epilepsy studied had experienced serious injuries.

A tale behind the rectum.

Tailgut cysts, also called benign retrorectal hamartomas, are uncommon developmental cysts found behind the rectum. Here, we present a rare case of a tailgut cyst associated with uterine anomaly, sacral and vertebral anomalies and vascular duplication, in a young lady who presented with constipation and infertility.

Hippocampal activations in mesial temporal lobe epilepsy due to hippocampal sclerosis- an observational study on intramural encoding-delayed recall paradigms using task-based memory fMRI.

OBJECTIVES: To validate concurrent utility of within-scanner encoding and delayed recognition-memory paradigms to ascertain hippocampal activations during task-based memory fMRI. METHODS: Memory paradigms were designed for faces, word-pairs and abstract designs. A deep-encoding task was designed comprising of a total of 9 cycles run within a 1.5T MRI scanner. A recall session was performed after 1 h within the scanner using an event-related design. Group analysis was done with 'correct-incorrect' responses applied as parametric modulators in Statistical Parametric Mapping version 8 using boot-strap method to enable estimation of laterality indices (LI) using custom anatomical masks involving the medio-basal temporal structures. RESULTS: Twenty seven subjects with drug-resistant mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE-HS) [17 patients of left-MTLE and 10 patients of right-MTLE] and 21 right handed age-matched healthy controls (HC) were recruited. For the encoding paradigm blood oxygen level dependent (BOLD) responses in HC demonstrated right laterality for faces, left laterality for word pairs, and bilaterality for design encoding over the regions of interest. Both right and left MTLE-HS groups revealed left lateralisation for word-pair encoding, bilateral activation for face encoding, with design encoding in right MTLE-HS demonstrating a left shift. As opposed to lateralization shown in controls, group analysis of cued-recall BOLD signals acquired within scanner in left MTLE-HS demonstrated right lateralization for word-pairs with bilaterality for faces and designs. The right MTLE-HS group demonstrated bilateral activations for faces, word-pairs and designs. CONCLUSION: Recall-based fMRI paradigms indicate hippocampal plasticity in MTLE-HS, maximal for word-pair associate recall tasks.

Reversible periictal MRI abnormalities: clinical correlates and long-term outcome in 12 patients.

Although a wide spectrum of reversible periictal magnetic resonance imaging (MRI) abnormalities (RPMA) are being increasingly identified, the clinicians are often in a dilemma about their localization significance. This prompted us to analyze the clinical, MRI, electroencephalographic (EEG) and follow-up data of 12 patients with RPMA seen in a tertiary referral epilepsy center. RPMA occurred after a single or a cluster of focal seizures with or without secondary generalization. The interictal and ictal EEG abnormalities were localized to the site of RPMA in nine patients. RPMA involved areas remote from the site of EEG abnormalities in four patients. We have developed a comprehensive classification to account for the wide spectrum of RPMA involving gray matter, white matter and leptomeninges with or without contrast enhancement or mass effect. Follow-up MRIs showed complete resolution of RPMA in all, except in four patients, who developed residual focal atrophy. During median follow-up period of 3 years, recurrence of RPMA was observed in two patients. Diffusion weighted MRI in two patients and histopathological finding in one patient favored causal role of hypoxia in the pathogenesis of RPMA. Our observations help to understand the electroclinical profile, radiological spectrum, localization significance and natural history of RPMA better.

Emergent EEG is helpful in neurology critical care practice.

OBJECTIVE: Emergent EEG (eEEG) is increasingly used in critical care practice related to neurological disorders although it involves considerable reorganization in the neurophysiology department at high cost. There is little data regarding the usefulness of eEEG in acute care situations. Our objective was to audit the practice and utility of eEEG in critical care practice in a developing country. METHODS: This study was carried out in a tertiary care neurological center situated in a developing country. We had defined eEEG as any EEG performed on a non-elective basis upon request from a clinician for a seemingly emergency indication. All eEEGs performed in the neurophysiology service between October 2002 and September 2003 were reviewed. Referral diagnosis, delay in execution, final diagnosis and outcome were analyzed. eEEG was classified as useful if it clinched a diagnosis, excluded a specific diagnosis or helped in management. Statistical analysis was performed using the chi2 test or Fisher's exact test when indicated. The referral diagnosis and eEEG characteristics were correlated with the utility of the eEEG. Those with P-value <0.05 were considered significant. RESULTS: There were 286 eEEGs (males 160, mean age 40.6 +/- 23.5 years) among 2798 EEGs (10.2%) performed in the service. eEEG was performed within 24 h in 241 instances and the mean interval from request to formal reporting was 1.13 days. In 62.1% instances eEEG was classified as useful. Usefulness varied according to the referral diagnosis: status epilepticus (n = 41, 100% useful; P = 0.000), brain death (n = 28, 100% useful; P = 0.000), nonconvulsive status (n = 54, 96.3% useful; P = 0.000), recurrent seizures (n = 42, 81% useful; P = 0.006), hypoxic encephalopathy (n = 36, 80.6% useful; P = 0.016), encephalitis (n = 63, 42.9% useful; P = 0.001), metabolic encephalopathy (n=64, 37.4% useful; P = 0.000) and acute demyelination (n = 20, 25% useful; P = 0.001). eEEG findings included epileptiform discharges (n=58), periodic lateralized epileptiform discharges (n=27), discrete seizures (n = 28), nonconvulsive status (n = 12), status epilepticus (n = 8), triphasic waves (n = 15), generalized suppression (n = 22), burst suppression (n = 9), alpha-theta coma (n = 7), electro cerebral silence (n = 2), focal and generalized slowing (n = 172), focal and generalized nonspecific dysfunction (n = 87), and no abnormalities (n = 24). Only discrete seizures (P = 0.000), nonconvulsive status (P = 0.004), generalized suppression (P = 0.004) epileptiform discharges (P = 0.047), and alpha-theta coma pattern (P = 0.047) were significantly correlated with usefulness. CONCLUSIONS: eEEG provided data that influenced clinical decision-making in the setting of epilepsy related situations, hypoxic encephalopathy and brain death examination. SIGNIFICANCE: eEEG can provide useful information in selected clinical situations in neurological critical care. The service needs to be called upon judiciously in order to improve the efficacy of this service.

Neural tube defects: pathogenesis and folate metabolism.

Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex aetio-pathogenesis. Animal studies indicate that there may be four sites of initiation of neural tube closure (NTC). Selective involvement of these sites may lead to defects varying from anencephaly to spina bifida. The NTC involves formation of medial and dorsolateral hinge points, convergent extension and a zipper release process. Proliferation and migration of neuroectodermal cells and its morphological changes brought about by microfilaments and other cytoskeletal proteins mediate NTC. Genetic, nutritional and teratogenic mechanisms have been implicated in the pathogenesis of NTDs. Folate is an important component in one carbon metabolism that provides active moieties for synthesis of nucleic acids and proteins. Several gene defects affecting enzymes and proteins involved in transport and metabolism of folate have been associated with NTDs. It may be possible in future, to identify individuals at higher risk of NTDs by genetic studies. Epidemiological and clinical studies have shown that dietary supplementation or food fortification with folic acid would reduce the incidence of NTDs. The protective effect of folic acid may be by overcoming these metabolic blocks through unidentified mechanisms. Genetic and biochemical studies on foetal cells may supplement currently available prenatal tests to diagnose NTDs. Antiepileptic drugs (AEDs), particularly valproate and carbamazepine have been shown to increase the risk of NTDs by possibly increasing the oxidative stress and deranging the folate metabolism. Accordingly, it is recommended that all women taking AEDs may use 1-5 mg folic acid daily in the pre conception period and through pregnancy.

Neurological aspects of eclampsia.

Eclampsia accounts for a third of maternal mortality in developing countries. The neurological manifestations of eclampsia consist of seizures and alteration of sensorium or coma on a background of pre-eclampsia. Occasionally there can be focal neurological deficits too. Recent studies with CT scan and MRI have demonstrated the presence of cerebral edema and/or cerebral hemorrhage in eclampsia. EEG in patients with eclampsia has revealed evidence of diffuse cerebral dysfunction (delta waves) and epileptiform transients (spikes or sharp waves). There is also evidence of extensive vasculopathy within the brain parenchyma. A variety of mechanisms have been suggested to explain these changes, the most important being failure of autoregulation of cerebral blood flow that leads to cerebral edema and hemorrhage. There is considerable controversy regarding the treatment of seizures in eclampsia. Recent studies have shown that magnesium sulfate is superior to phenytoin or diazepam in the treatment of eclamptic seizures and prevention of eclamptic seizures in women with pre-eclampsia.

Epilepsy care in six Indian cities: a multicenter study on management and service.

BACKGROUND: Epilepsy care in developing countries is lagging behind than in the developed countries. Precise data on delivery of neurological services for epilepsy is essential to optimize the medical services for epilepsy care with limited resources. OBJECTIVE: This study was carried out in order to examine the management practices and utilization of various medical services for epilepsy in different parts of India. METHODOLOGY: University centers with epilepsy clinics, one each from six states of India, had participated in this study. Demographic data, clinical details, and data on epilepsy care were collected simultaneously on standard proforma. RESULTS: Data on 285 patients with epilepsy (generalized epilepsy: 49.1%, localization-related epilepsy: 49.9%, others: 1%) were included. Mean age of onset of epilepsy was 14.8+11.1 years. Mean delay in diagnosis was 1.5+/-4 years. Mean distance from place of residence to the consulting neurologist was 70+/-82 km. Medical consultations before referral to epilepsy center included general practitioners (54.1%) and specialists (43.3%). Very few patients received services from clinical psychologist or social worker. Investigations included, EEG (63.2%), CT Scan (36.2%). MRI brain (8.5%) and video EEG (2.1%) were limited to a few. Nearly 75.5% were on monotherapy. Newer Anti-Epileptic Drugs (AEDs) were used only in less than 5% patients. CONCLUSION: The services for epilepsy are urban-based and there is underutilization of services, general practitioners and specialists. Newer AEDs (although expensive) are gradually emerging in Indian market. Facilities for epilepsy surgery, therapeutic drug monitoring and services of clinical psychologist or medical social workers are limited.

Melanotic differentiation in dysembryoplastic neuroepithelial tumor.

Dysembryoplastic neuroepithelial tumor (DNT) is an uncommon intracranial tumor which is usually encountered in patients with medically intractable complex partial seizures of temporal lobe origin. Melanotic differentiation in a DNT has not been reported previously. Herewith we report a case of DNT with unique melanotic differentiation in a 23-year-old female who presented with medically intractable epilepsy. She underwent craniotomy and tumor decompression with a good outcome. We present the histopathological features of DNT with melanotic differentiation and discuss its prognostic significance.

Reversible non enhancing lesions without focal neurological deficits in eclampsia.

Nine patients with eclampsia, were subjected to computerized tomographic scan (CT scan) of the head to ascertain the changes in the brain that accompany seizures and encephalopathy of eclampsia. Only those patients who had a seizure within the past 24 h were included in this study. None of the patients had any focal neurological deficit. Six of the nine patients had abnormal findings on CT scan consisting of multiple non enhancing hypodensities in the cerebral white matter. One patient also had subependymal haemorrhage over the lateral ventricle. These changes were found to have disappeared when the CT scan was repeated on the seventh day. There was no correlation between the mean arterial blood pressure or the number of seizures and the presence of hypodensities in the brain. These findings suggest that subclinical changes in the form of reversible hypodensities and rarely bleeding can occur in eclampsia even when patients have no focal neurological deficits. It appears that these lesions represent focal areas of cerebral oedema, secondary to failure of autoregulation of cerebral blood flow.

Psychosocial and economic problems of parents of children with epilepsy.

The parents of children with epilepsy (PCE) face multiple psychosocial and economic problems that are often neglected. We undertook this study to ascertain these problems among the patients attending a tertiary referral center for epilepsy in India. A structured questionnaire was administrated to parents of 50 children aged between 5-10 years and having epilepsy for more than 1 year's duration. Some 52% of the children had partial epilepsy whilst the remaining had generalized epilepsy. The median seizure frequency was one per 6 months. The majority of the patients (86%) were living in villages. The family income was less than 1000 Rs per month (1 USD = 42 INR) for 66% of the patients. A decline in social activities, after the onset of epilepsy in their children, was reported by 80% of the parents. Daily routines were significantly affected in over 75% of the parents. Parents had been experiencing frustration (52%) and hopelessness (76%), whilst 60% were in financial difficulties. The most important item of expenditure was cost of drugs or cost of travel to hospital for 54% and 36% parents respectively. Impaired emotional status and poor social adaptation were co-related with the severity of epilepsy (frequent seizures/generalized seizures/attention disorder) and low economic status of the parents. These observations need to be borne in mind while organizing rehabilitation programs for epilepsy.

Mortality among epilepsy patients attending a tertiary referral center in a developing country.

Epilepsy is associated with excess mortality of two to three times in developed countries. Precise epidemiological data on mortality and cause of death are not available from India or most other developing countries. This study was carried out to estimate the mortality rates and to identify the demographic and clinical characteristics associated with mortality in a hospital based cohort of epilepsy patients. A cohort of patients enrolled in the epilepsy clinic in 1985 was followed up till 1997 (12 years). The mortality rate, demographic and clinical correlate of mortality were analysed for 246 patients (men 161, women 85) who had complete data. Cause of death was not examined in this study. Eighteen (men 15, women 3) of the 246 patients (7.3%) had died during the follow up period of 12 years. The crude death rate for the state of Kerala for the year 1990 (mid period of the study) was 5.9 per thousand population. The demographic and clinical characteristics of those who died (corresponding figures for survivors are given in brackets) were as follows: mean age 33.6 years (22.8 years), presence of abnormal neurological examination 38.9% (15.4%), mental retardation 33.3% (12.8%), abnormal CT scan 38% (21.5%). Regarding the seizure frequency at the time of enrollment and eventual mortality, there were no deaths among patients who had an Engel's seizure score of less than or equal to 4 (no seizures or nocturnal seizures only). The mortality was 5% for an Engel's score of 5 or 6 and 11% for an Engel's score greater than 6. Within the group with epilepsy, higher seizure frequency at the time of initial evaluation was associated with excess mortality. Abnormality on neurological examination, older age group and male sex were other factors that correlated with excess mortality.

Management and referral patterns of epilepsy in india.

Evaluation of management and referral pattern is very important in the organization of medical services for epilepsy. In order to study the management and referral pattern of epilepsy, a structured questionnaire was administered to 100 epilepsy patients attending a referral hospital in Kerala State, India. Of these, 61.4% of them were living in villages; 65% had a monthly income less than Rs. 1000. Seventy-five percent of the patients had generalized seizures. The mean delay in diagnosis was more for those from villages (13.5 months) as compared to those from urban areas (6.4 months) and for women (11.7 months) as compared to men (7.8 months). Previous consultation before referral to this Institute included general practitioners (61%), specialists (50%) and neurologist or neurosurgeon (27%). Eighty-eight patients have had EEG and 51 patients have had CT Scans. Thirty-nine per cent of patients required hospitalization for control of seizures that was significantly (P = 0.036) higher among those living in an urban area. Seventy-five per cent of patients were collecting drugs from private pharmacies. No patient was collecting antiepileptic drugs from government institutions even though such a facility was available within 5 km of their residence. This study has revealed that the organization and delivery of neurological services for epilepsy leaves much to be desired.

First ever seizures in the elderly: a seven-year follow-up study.

The clinical characteristics and prognosis of first ever seizures among the elderly (aged 65 years or more) were ascertained by following up a cohort of patients for 7 years. Twenty-three patients (mean age, 69.9 +/- 4.9 years) were registered in the Neurology Service between January 1988 and March 1989. Twelve patients had partial seizures with or without generalization. Three patients had status epilepticus, whereas ten had presented for single seizure. On presentation 61.9% patients had neurological deficits and 73.9% had one or more systemic disorder. Head computerized tomography scans were abnormal in 17 cases. Seizures were attributed to acute stroke (26.1%), trauma (8.7%), subdural haematoma, degenerative diseases of the brain, cerebral metastasis, or central nervous system infections. The cause was unknown in 43.5% cases. At the end of 7 years, follow-up was complete for 15 patients (65.2%). The mean duration of follow-up was 68.6 +/- 28.7 months. Eight (53.3%) patients had died. Nine patients (60%) had attained 2-year remission of which three remained seizure free throughout. Six of the seven living patients were continuing antiepileptic drugs treatment. Forty per cent of them were dependent on others for the activities of daily life.

Epilepsia partialis continua--a clinical and electroencephalography study.

Epilepsia partialis continua (EPC) is a rare type of localization-related motor epilepsy. Clinical spectrum, electroencephalography (EEG) characteristics and various prognostic factors in EPC were studied in 20 patients. Patients who fulfilled the criteria for EPC between the years 1985 and 1999 were included in this retrospective and prospective study. The mean age was 18 years (range 5 months-70 years). Eleven patients (55%) had Type 1 EPC and in the remaining nine (45%) patients there were features of Type 2 EPC. Among children Rasmussen's encephalitis and viral encephalitis were the commonest cause for EPC. Encephalitis and vascular aetiology were frequently observed in adults. Tuberculous meningitis and tuberculomas occurred evenly in both the groups. The cause was unknown in two cases. Focal EEG abnormalities commonly consisted of discrete spikes, sharp waves (or) slow wave activity and periodic lateralized epileptiform discharges. The mean duration of follow up was 9.6 months with a range between 1 month and 4 years. Cognitive decline, motor deficits and pharmacoresistance to drugs were significantly seen among children with Type 2 EPC. Patients with Type 1 EPC had mild impairment of functional status with good response to treatment. The long-term prognosis depends upon the underlying cause.

Nipple reconstruction with a new local tissue flap.

We present a one-staged local cutaneous-fat flap for nipple reconstruction. It has proven reliable in producing a geometrically correct nipple without complication. It represents a modification of existing cutaneous or dermal-fat flaps with theoretical and apparent benefits inherent in its design.