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.

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.

Long-term visual outcome in idiopathic intracranial hypertension.

OBJECTIVE: To characterize the course, outcome, and risk of relapse or late worsening in a clearly defined cohort of idiopathic intracranial hypertension (IIH) over a long period of follow-up. MATERIALS AND METHODS: Retrospective chart review of patients with definite IIH was evaluated at the Sree Chitra Tirunal Institute for Medical Sciences and Technology between 1998 and 2006. Patients' demographic data, clinical, neuro-ophthalmic examinations, and treatment details were abstracted. Patients were further categorized into three groups based on whether they improved, worsened, or relapsed on follow-up. Final visual outcome of each patient was defined according to grading of the worse eye at the last visit. Statistical analysis included t test to compare group means and chi-square test to compare proportions. RESULTS: Of the 43 women included, visual impairment was observed in 80 eyes (93%) at presentation and it was moderate to severe in 14%. The mean CSF opening pressure at presentation did not differ significantly in those with visual impairment compared to those with normal vision. Those having early severe visual impairment had significantly higher (P = 0.015) likelihood of severe visual impairment on last follow-up. Of the total, 34 patients (79%) improved, 4 (9.3%) relapsed on follow-up after period of stability, and 5 (11.6%) worsened over 56 months follow-up (range, 26-132 months). The groups were comparable, except those who improved were younger (P<0.05). At last examination, 9% had significant vision loss. CONCLUSION: IIH patients can have delayed worsening or relapses and about tenth of patients can have permanent visual loss early or late in the course of the disease. All patients with IIH need to be kept under long-term follow-up, with regular monitoring of visual functions.

Central nervous system tuberculosis.

Central nervous system (CNS) involvement, one of the most devastating clinical manifestations of tuberculosis (TB) is noted in 5 to 10% of extrapulmonary TB cases, and accounts for approximately 1% of all TB cases. Definitive diagnosis of tuberculous meningitis (TBM) depends upon the detection of the tubercle bacilli in the CSF. Every patient with TBM should preferably be evaluated by imaging with contrast enhanced CT either before or within the first 48 hours of treatment. An extra-neural focus of tuberculosis should be sought clinically and radiologically in all patients with CNS TB as it may indicate safer and more accessible sites for diagnostic samplings. A minimum of 10 months treatment is warranted, prompted by the uncertain influences of disease severity, CNS drug penetration, undetected drug resistance and patient compliance. All patients with TB meningitis may receive adjunctive corticosteroids at presentation regardless of disease severity even for those with HIV infection. Drug resistance is strongly associated with previous treatment. The key principle of managing drug-resistant TB is never to add a single drug to a failing regimen. Early ventriculo-peritoneal shunting should be considered in those with hydrocephalus failing medical management. The single most important determinant of outcome is the stage of tuberculous meningitis at which treatment has been started.

Risk of major congenital malformations in the offsprings of women with epilepsy is not related to family history.

UNLABELLED: We aimed to ascertain whether family history of major congenital malformations (MCMs) was increased in women with epilepsy (WWE) compared to controls (spouses) and whether family history of MCM was associated with occurrence of MCM in the offspring. PATIENTS AND METHODS: Women enrolled in the Kerala Registry of Epilepsy and Pregnancy were probands of this study. The control group comprised of unaffected spouses and their families. We interviewed the probands and spouses to construct detailed pedigree charts with information on MCM. All live born infants of WWE underwent clinical examination, echocardiography and ultrasonography. RESULTS: Data were collected for 11,777 family members of probands (n=573) and 10,832 family members of controls (n=550). Family history of MCM was positive for 84 probands (0.71%) and 64 controls (0.59%). Corresponding figures for first degree relatives were 32 out of 2717 for probands (1.18%) and 27 out of 2992 for controls (0.90%). Among the second degree relatives 52 out of 9060 for probands (0.71%) and 64 out of 10,832 for the controls (0.50%) had history of MCM. These differences were not statistically significant (p value=0.29, 0.37 and 0.42, respectively). There was no significant difference in the frequency of MCM between probands with generalized epilepsy and localization related epilepsy. Out of the 426 live born infants of the probands, 44 had MCM; two with family history and 42 without family history (OR 0.74; 95% CI 0.19-3.26). CONCLUSIONS: WWE of Asian Indian origin have no familial tendency for MCM and the offsprings with family history have no increased risk of MCM.

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.

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.

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.

Cardiac malformations are increased in infants of mothers with epilepsy.

We aimed to ascertain the prevalence of cardiac malformation (CM) and its association with antenatal exposure to an antiepileptic drug (AED) in infants of mothers with epilepsy (IMEs). Women with epilepsy (WWE) are enrolled in Kerala Registry of Epilepsy and Pregnancy (KREP) in the prepregnancy or early pregnancy period and are followed up with a standard protocol until the IMEs are 6 years old. At 3 months postpartum, a cardiologist, blinded to the AED exposure, carried out a clinical examination and echocardiography on all live-born babies. Patent foramen ovale (PFO) and interatrial septal defects of < 5 mm in size were excluded from CM. Details of maternal epilepsy, folate usage, AED exposure in the first trimester, and newborn characteristics were abstracted from the records of the KREP. We examined 462 babies. Maternal epilepsy was generalized in 201 (43.50%) or localization related in 241 (52.2%). The AED exposure was monotherapy in 262 (56.7%)--carbamazepine (112), valproate (71), phenobarbitone (43), phenytoin (31), and clonazepam (2)--and polytherapy in 126 (27.3%). Seventy-four infants (16.01%) had no AED exposure. There were 36 infants with CM (7.8%; 95% confidence interval: 5.5-10.6). CMs included atrial septal defect (26; 72.2%), tetrology of Fallot (3; 8.3%), patent ductus arteriosus and pulmonic stenosis (2 each; 5.6%), and ventricular septal defect, tricuspid regurgitation, transposition of great arteries (1 each; 2.8%). CMs were significantly more for IMEs with premature birth (p < .003). There was no association between CM and maternal age, epilepsy syndrome, seizure frequency during pregnancy, and folate use. CMs were more frequent with polytherapy (13; 10.3%) compared to monotherapy (17; 6.5%). Those with valproate exposure had a trend (not statistically significant) toward higher frequency of CM compared to IMEs on other AEDs as monotherapy.

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.

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.

Management of epilepsy and pregnancy.

Epilepsy is recognized as the commonest serious neurological disorder in the world. Women with epilepsy (WWE) experience several gender-related physical and social problems. They constitute high obstetric risk because of reduced fertility, risk of seizures during pregnancy and complications of pregnancy. Hormonal and other factors can alter the pharmacokinetics of antiepileptic drugs (AED) during pregnancy and puerperium. Antenatal exposure to AEDs, particularly at higher dosage and in polytherapy, increases the risk of fetal malformation. Recent reports raise the possibility of selective developmental language deficits and neurocognitive deficits with antenatal exposure to AEDs. There are concerns regarding the effect of traces of AEDs that pass to the infant during breast-feeding. The pre conception management is the cornerstone for epilepsy care in WWE. A careful reappraisal of each case should ascertain the diagnosis, the need for continued AED therapy, selection of appropriate AEDs, optimization of the dosage and prescription of folic acid. During pregnancy, the fetal status needs to be monitored with estimation of serum a-feto-protein and ultrasound screening for malformations. The dosage of AEDs can be adjusted according to clinical requirement and blood levels of AEDs. Several institutions recommend oral vitamin K toward the end of pregnancy when enzyme-inducing AEDs are prescribed because the latter may potentially predispose the new born to hemorrhagic disease, but recent reports indicate that such a risk is practically negligible. WWE who are using enzyme-inducing AEDs (phenobarbitone, primidone, phenytoin, carbamazepine and oxcarbazepine) need to know that these AEDs may lead to failure of oral contraception.

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.

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.

Finger tapping activates spikes in benign epilepsy with centro-temporal spikes.

A case of benign epilepsy with centro-temporal spikes (BECT) is reported, in whom tapping of fingures activated typical spikes.

Economic burden of epilepsy in India.

PURPOSE: The economic burden due to epilepsy is not adequately examined in developing countries. Cost estimates are very important in health care planning and delivery of services. We have estimated the direct and some of the indirect costs of epilepsy in India. METHODS: Epilepsy centers attached to University hospitals in six states of India participated in this study. Data on clinical characteristics, utilization of medical services, and costs were collected in a standardized format. RESULTS: There were 285 patients (mean age, 22.6 + 12.5 years) drawn from six centers in this study. The annual cost of epilepsy per patient was INR 13,755 (USD, 344). The direct cost was INR 3,725 (USD, 93), and the indirect cost was INR 10,031 (USD, 251). Direct cost included medical consultations (INR 329), laboratory services (INR 271), hospitalization charges (INR 316), and cost of travel to clinics (INR 659). The indirect cost included the cost of lost productivity due to seizures, its complications, or attendance to clinics. There are approximately 5 million people with epilepsy in India. The economic burden due to epilepsy to the nation is to the tune of INR 68.75 billion (USD, 1.7 billion). CONCLUSIONS: The annual economic burden of epilepsy in India is 88.2% of GNP per capita and 0.5% of the GNP.