Exploring the Serum Level of RE1 Silencing Transcription Factor in Alzheimer's Disease

Objectives:The aim of this study was to evaluate the serum RE1 silencing transcription factor (REST) level in Alzheimer's disease (AD), mild cognitive impairment (MCI), and elderly controls by using surface plasmon resonance (SPR) technology. Materials and Methods?In this case–control study of 133 subjects, 49 patients with AD, 49 patients with MCI, and 35 elderly controls were recruited. The REST protein concentrations were evaluated by SPR. The resonance unit for each sample was recorded and the concentration of serum REST of study group was derived from the standard curve. All the experiments were done in triplicates. Statistical analysis was done and p-value of < 0.05 was considered as statistically significant. Results?A significant difference was observed in the Montreal Cognitive Assessment score, Hindi Mental State Examination scale (HMSE) score education, disease duration, and gender among the groups. A significant (p>0.0001) difference in the duration of disease between AD and MCI was observed. It was observed that the mean concentration of serum REST was not significantly (p?=?0.266) different among the groups. Conclusion?This study first time evaluated the serum levels of REST in AD, MCI and age-matched elderly controls. The rest levels were similar in all groups; however, it can provide a new direction to future blood-based biomarker studies of REST.

Yoga nidra practice shows improvement in sleep in patients with chronic insomnia: A randomized controlled trial

BACKGROUND Yoga nidra is practised by sages for sleep. The practice is simple to use and has been clearly laid out, but its role in the treatment of chronic insomnia has not been well studied. METHODS In this randomized parallel-design study conducted during 2012–16, we enrolled 41 patients with chronic insomnia to receive conventional intervention of cognitive behavioural therapy for insomnia (n=20) or yoga nidra (n=21). Outcome measures were both subjective using a sleep diary and objective using polysomnography (PSG). Salivary cortisol levels were also measured. PSG was done before the intervention in all patients and repeated only in those who volunteered for the same. RESULTS Both interventions showed an improvement in subjective total sleep time (TST), sleep efficiency, wake after sleep onset, reduction in total wake duration and enhancement in subjective sleep quality. Objectively, both the interventions improved TST and total wake duration and increased N1% of TST. Yoga nidra showed marked improvement in N2% and N3% in TST. Salivary cortisol reduced statistically significantly after yoga nidra (p=0.041). CONCLUSION Improvement of N3 sleep, total wake duration and subjective sleep quality occurred following yoga nidra practice. Yoga nidra practice can be used for treatment of chronic insomnia after supervised practice sessions.

Evaluation of memory in persons with mesial temporal lobe sclerosis: A combined fMRI and VBM study

Persons with drug refractory TLE have the option of being managed by surgery. They may develop memoryimpairment with specific etiology of mesial temporal sclerosis and anterior temporal lobe resection (ATLR).The study evaluated the semantic verbal memory outcomes in pre- and post-surgery temporal lobe epilepsy(TLE) patients using functional MRI and voxel morphometric methods. Twenty consecutive persons withdrug-resistant epilepsy (DRE) and 20 healthy controls were recruited after obtaining the institute ethicsapproval. The fMRI scans were performed on a 1.5 T MR Scanner using standardized semantic verbal memorytasks using a native Hindi paradigm, before and after an anterior temporal lobectomy (in cases). A task-basedfunctional connectivity (FC) was estimated using a conn toolbox. Data analysis was carried out using thestatistical parametric imaging (SPM12) and CAT12 toolbox. Post-surgery TLE group showed increased robustFC in the right middle and posterior temporal regions as compared to pre-surgery session. A significantreduction in grey matter volume was observed in the left temporal lobe post-operatively as compared to presurgery and healthy control groups. In the post-surgery TLE group, neuropsychological scores were reduced inspecific PGI domains such as visuospatial, working memory, and executive functioning. Our results may helpin understanding of memory reorganization in TLE post-operatively.

Carbamazepine, Sodium Valproate and Levetiracetam Modulate Wnt Inhibitors in Indian Women with Epilepsy

Background:Antiepileptic drug (AED) therapy has been claimed to deteriorate bone health. Majority of the research was inclined towards vitamin-D deficiency as the patho-mechanism. However, after the role of Wnt in bone metabolism was discovered, it has paved way for investigating the role of Wnt inhibitors in mediating effects on bone accrual. Recently, we have reported the modulation of two Wnt inhibitors, sclerostin and dickkopf-1 (DKK-1), following AED therapy in Indian women with epilepsy, however, the subgroup analysis for individual drug is elucidated in this report. Methods: Individual analysis for our earlier cross-sectional study on three AEDs, carbamazepine (CBZ), sodium valproate (SVP) and levetiracetam (LTM), on sclerostin and dickkopf-1, and their correlation with receptor activator of nuclear factor kappaB ligand (RANKL) and serum 25-hydroxy vitamin D (25OHD) was assessed in Indian women with epilepsy. Results: We observed enhanced sclerostin and 25OHD levels with all three AEDs while serum RANKL was higher with SVP and LTM only. Further, serum DKK-1 levels were lowered with CBZ and LTM. Sclerostin showed a positive correlation with RANKL in CBZ group, while DKK-1 presented no such relationship

Comparison of body composition in persons with epilepsy on conventional & new antiepileptic drugs.

Background & objectives: Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs. Methods: The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed. Results: Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, P<0.05). In comparison with control, AEDs monotherapy groups had no significant difference, except higher LDM and ECW in VPA group. Among groups based on conventional and newer AEDs, there was no significant difference in body composition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (P<0.01). Interpretation & conclusions: The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701).

Effect of clobazam as add-on antiepileptic drug in patients with epilepsy.

Background & objectives: The use of clobazam in epilepsy has increased since its introduction in 1975. However, it has not been audited for its overall usefulness in Indian set up. The present study was aimed to evaluate usage pattern, retention rate, effectiveness and tolerability of clobazam during routine practice in an outpatient epilepsy clinic of a tertiary care hospital in New Delhi, India. Methods: This study was performed on the patients prescribed antiepileptic medication who had clobazam as last added drug in their treatment regimen during October 2010 - March 2012. These patients were followed up for two OPD visits. The primary points evaluated were retention rate, percentage of seizure-free patients and reasons for discontinuing clobazam. Results: oOf the 417 consecutive patients, 132 (31.7%) were on clobazam treatment for more than four years (median 6 yr, range 4-15 yr). No seizure for previous 12 months was considered as seizure free and was observed in 151 (36.2%) patients. There was no improvement in seizure control in 32 (7.7%) patients. A decrease in seizure severity without any change in seizure frequency was observed in 76 (18.2%) patients. Clobazam was discontinued by 15 (3.6%) patients due to complaints like drowsiness (13), fatigue/tiredness (8), headache (6), poor memory (6), irritable behaviour (5), abdominal pain (3) and dizziness (3). Interpretation & conclusions: oOur results provide valuable information about the clinical use of clobazam as add-on antiepileptic drug therapy in the management of patients with epilepsy.

Prevalence of systemic co-morbidities in patients with various grades of diabetic retinopathy.

Background & objectives: Though diabetes affects multiple organs, most studies highlight the occurence of only one complication in isolation. We conducted a hospital-based study to estimate the co-existence of significant systemic co-morbid conditions in patients with varying grades of diabetic retinopathy. Methods: A total of 170 consecutive patients with diabetic retinopathy were prospectively recruited for the study between June 2009 to June 2010 at a tertiary care eye centre in north India. Retinopathy was graded by fundus biomicroscopy and fundus photography and classified into three categories (mild-moderate nonproliferative retinopathy, proliferative retinopathy requiring only laser and proliferative retinopathy requiring surgery). Nephropathy was classified by calculating the six variable estimated glomerular filtration rate (eGFR) for all patients. Nerve conduction studies and clinical assessment were used to determine presence of neuropathy. Co-existence of macrovascular disease and peripheral vascular disease was also ascertained. Results: The percentages of patients with overt nephropathy in the three groups were 19.2, 38.0 and 41.2, respectively. Significant linear trends were observed for serum creatinine (P=0.004), albumin (P=0.017) and eGFR (P=0.030). A higher per cent had abnormal nerve conduction on electrophysiology than that diagnosed clinically (65.4 vs. 44.2, 76.0 vs. 40.0 and 64.8 vs. 48.6, respectively). The odds ratio (95% CI) for co-existence of nephropathy, neuropathy, CVA (cerebrovascular accidents) and PVD (peripheral vascular disease) was 2.9, 0.9, 4.8 and 3.5, respectively. Independent of retinopathy severity, patients with clinically significant macular oedema (CSME) had a higher percentage of nephropathy (pP < 0.005). Interpretation & conclusions: The co-existence of overt nephropathy, nerve conduction based neuropathy and macrovascular co-morbidity in patients with early grades of diabetic retinopathy was significant. Screening for overt nephropathy by eGFR should be considered in all patients with clinically significant macular oedema.

Prevalence of symptomatic and asymptomatic coronary artery disease in patients with stroke.

Background. Studies have shown that myocardial infarction is a leading cause of death in patients recovering from stroke or transient ischaemic attacks. We aimed to study the prevalence of symptomatic and asymptomatic coronary artery disease (CAD) in patients with stroke. Methods. Eighty-six patients with stroke were evaluated for risk factors and presence of CAD. Patients without a previous diagnosis of CAD underwent stress–rest gated technetium-99m (Tc99m) tetrofosmin myocardial perfusion SPECT (MPS) scan to estimate the presence or absence of a reversible perfusion deficit. Results. Thirty-three patients (clinically asymptomatic for CAD) did not consent for the MPS scan. Among the remaining 53 patients, 13 patients had been previously diagnosed to have CAD, 8 patients were suspected to have underlying CAD and 32 patients were asymptomatic. Among the patients with suspected CAD, 2 had abnormal MPS scans and one had triple-vessel disease on coronary angiography. Of the asymptomatic patients, 6 had CAD. The overall proportion of CAD among patients with stroke was 41.5% (22/53) and that of asymptomatic CAD 18.8% (6/32). Conclusion. A considerable number of patients with stroke may have associated CAD. An optimal management strategy in stroke patients who have silent CAD may improve clinical outcomes.

Autologous intravenous bone marrow mononuclear cell therapy for patients with subacute ischaemic stroke: a pilot study.

Background & objectives: Bone marrow mononuclear cell therapy has emerged as one of the option for the treatment of Stroke. Several preclinical studies have shown that the treatment with mononuclear cell (MNCs) can reduce the infarct size and improve the functional outcome. We evaluated the feasibility, safety and clinical outcome of administering bone marrow mononuclear cell (MNCs) intravenously to patients with subacute ischaemic stroke. Methods: In a non-randomized phase-I clinical study, 11 consecutive, eligible and consenting patients, aged 30-70 yr with ischaemic stroke involving anterior circulation within 7 to 30 days of onset of stroke were included. Bone marrow was aspirated from iliac crest and the harvested mononuclear cells were infused into antecubital vein. Outcomes measured for safety included immediate reactions after cell infusion and evidence of tumour formation at one year in whole body PET scan. Patients were followed at week 1, 4-6, 24 and 52 to determine clinical progress using National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), MRI, EEG and PET. Feasibility outcomes included target-dose feasibility. Favourable clinical outcome was defined as mRS score of 2 or less or BI score of 75 to 100 at six months after stem cell therapy. Results: Between September 2006 and April 2007, 11 patients were infused with bone-marrow mononuclear cells (mean 80 million with CD-34+ mean 0.92 million). Protocol was target-dose feasible in 9 patients (82%). FDG-PET scan at 24 and 52 wk in nine patients did not reveal evidence of tumour formation. Seven patients had favourable clinical outcome. Interpretation & conclusions: Intravenous bone marrow mononuclear cell therapy appears feasible and safe in patients with subacute ischaemic stroke. Further, a randomized controlled trial to examine its efficacy is being conducted.

Surgical outcome of cortical dysplasias presenting with chronic intractable epilepsy: A 10-year experience.

Background: There has been sparse description of cortical dysplasias (CDs) causing intractable epilepsy from India. Aim: Clinical retrospective study of CDs causing intractable epilepsy that underwent surgery. Materials and Methods: Fifty-seven cases of CDs reviewed (1995 till July 2006) are presented. All patients had intractable epilepsy, and underwent a complete epilepsy surgery workup (inter ictal electroencephalography (EEG), video EEG, MRI as per epilepsy protocol, SPECT {interictal, ictal with subtraction and co-registration when required}, and PET when necessary). Surgical treatment included a wide exposure of the pathology with a detailed electrocorticography under optimal anesthetic conditions. Mapping of the sensori-motor area was performed where indicated. Procedures included resection either alone or combined with multiple subpial transactions when extending into the eloquent areas. Results: Our study had 28 (49.12%) cases of isolated focal CDs, and 29 (50.67%) with dual pathology. Average age at the time of onset of seizures in our series was 7.04 years (three months to 24 years), and average age at the time of surgery was 10.97 years (eight months to 45 years). Among coexistent pathologies, one had associated MTS, 16 had coexistent gangliogliomas and 12 (dysembryonic neuroepithelial tumor) DNTs. At an average follow-up of 3.035 years (range 5-10 years), three patients were lost to follow-up. Fifty-one per cent (29/57) patients had a good outcome (Engel Grade I) and 26%(15/57) had a Grade II outcome. Conclusion: Cortical dysplasias have a good outcome if evaluated and managed with concordant electrical and imaging modalities.

Hemispherotomy for intractable epilepsy.

Context: Hemispherotomy is a surgical procedure for hemispheric disconnection. It is a technically demanding surgery. Our experience is presented here. Aims: To validate and compare the two techniques for hemispherotomy performed in patients with intractable epilepsies. Settings and Design: A retrospective study 2001-March 2007: Nineteen cases of hemispherotomies from a total of 462 cases operated for intractable epilepsy. Materials and Methods: All the cases operated for intractable epilepsy underwent a complete epilepsy surgery workup. Age range 4-23 years (mean 5.2 years), 14 males. The seizure frequency ranged from 2-200 episodes per day; four were in status; three in epilepsia partialis continua. The pathologies included Rasmussen's, hemimegelencephaly (unilateral hemispheric enlargement with severe cortical and subcortical changes), hemispheric cortical dysplasia, post-stroke, post-traumatic encephalomalacia and encephalopathy of unknown etiology. The techniques of surgery included vertical parasaggital approach and peri-insular hemispherotomy. Neuronavigation was used in seven cases. Results: Class I outcome [Engel's] was seen in 18 cases and Class II in one assessed at 32-198 weeks of follow-up. The four patients in status epilepticus had Class I outcome. Four patients had an initial worsening of weakness which improved to preoperative level in five to eight weeks. Power actually improved in three other patients at 32-36 weeks of follow-up, but hand grip weakness persisted. In all the other patients, power continued to be as in preoperative state. Cognitive profile improved in all patients and 11 cases returned back to school. Conclusions: Both techniques were equally effective, the procedure itself is very effective when indicated. Four of our cases were quite sick and were undertaken for this procedure on a semi-emergency basis.

Health-related quality of life using QOLIE-31: Before and after epilepsy surgery a prospective study at a tertiary care center.

Background: Outcome following epilepsy surgery has traditionally been measured in terms of relief of seizures. However, changes in health-related quality of life (HRQOL) after surgery for intractable epilepsy are also important to document. There are no studies on the Indian population which assess the outcome of epilepsy surgery in terms of HRQOL. Materials and Methods: We conducted a prospective study on the patients undergoing epilepsy surgery for intractable seizures, between February 2004 and May 2006 at our center. All patients cleared for epilepsy surgery by the epilepsy surgery team were taken up for study. All patients Results: Thirty-six patients satisfying the inclusion/exclusion criteria were included in the analysis. Twenty-nine of these (Group 1) had good seizure outcome (Engel 1 and 2), while seven patients (Group 2) had poor seizure outcome (Engel 3 and 4) at six months. Overall, 77% of all study patients were completely seizure-free at follow-up. There was no baseline difference in the seven domains of QOLIE-31 between the two groups. There was very significant improvement (P value> 0.005 using paired sample T test) in all the domains of QOLIE-31 in the good outcome group after surgery. Health-related quality of life improvement was seen in all the domains in the poor outcome group also, however, it was statistically significant only for the following parameters: seizure worry, overall QOL, emotional wellbeing, energy fatigue and social functioning domains. Improvement in seizure worry, overall QOL, emotional wellbeing and social functioning was significantly more in Group 1 as compared to Group 2. Conclusion: Complete seizure-free state after surgery is associated with very significant improvement in HRQOL parameters. Several, but not all parameters of HRQOL as assessed by QOLIE-31, improved after surgery even in the poor seizure outcome group. The improvement in domains of seizure worry, overall QOL, emotional wellbeing and social functioning is significantly more in those patients in whom complete seizure-free state is achieved.

Neuropathological spectrum of lesions associated with intractable epilepsies: a 10-year experience with a series of 153 resections.

BACKGROUND: Surgical management of intractable epilepsies is currently an established mode of therapy in various clinical settings. AIMS: To retrospectively evaluate the neuropathological findings in both temporal and extratemporal lobe resections in such patients. MATERIALS AND METHODS: The study included resected specimens from patients with intractable epilepsy managed at a tertiary care hospital of India, during a 10-year period (1995-2004). RESULTS: A total of 153 patients, with mean age of 19.4 years and male predominance (73.2%) were included in the study. Overall, there was a predilection for the temporal lobe (73.2%), while 41cases were extratemporal in location. On histopathology, mesial temporal sclerosis (MTS) (24.8%) was the commonest lesion, followed by tumors (19.6%) and isolated focal cortical dysplasia (FCD - 15.11%). Other less common findings included Rasmussen encephalitis, non-specific gliosis and vascular malformations. In addition, 20.9% (32 cases) had dual lesions, majority of which included FCD with ganglioglioma (15 cases) or with dysembryoplastic neuroepithelial tumor (12 cases). In the temporal lobe, neoplasms and dual lesions formed the majority (apart from MTS), unlike dual lesions followed by neoplasms and FCD, in the extratemporal location. CONCLUSION: This series demonstrates that most patients with chronic intractable epilepsy have significant histopathological findings and highlights the neuropathological spectrum of such lesions, in the Indian context. This was similar to that reported from the West, but different from the single Indian series available in the literature. Further, the overall profile of temporal lobe lesions was not different from the extratemporal ones.

Neuropathological spectrum of Rasmussen encephalitis.

BACKGROUND: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. AIMS: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. MATERIALS AND METHODS: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. RESULTS: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. CONCLUSION: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.

Clinical profile of migraineurs in a referral centre in India.

BACKGROUND: Migraine is one of the commonest of headache disorders presenting to neurologists the world over. Though the precise etiopathogenesis of migraine is still not completely understood, there are various studies speculating on the role of different genetic loci and various patterns of inheritance. OBJECTIVE: The present study was conducted to characterize the migraineurs presenting to a referral hospital in India and understand their possible modes of inheritance by clinical evaluation of family pedigree. METHODS: A questionnaire based, prospective study including consecutive patients was conducted in the department of Neurology at a tertiary referral center in India. All patients fulfilling the diagnostic criteria for migraine were enrolled and their characteristics noted. Other family members of those with a positive history of headache were also interviewed. RESULTS: A total of 198 migraineurs were interviewed from March 2001 to July 2002. The proportion of female migraineurs was higher, comprising 72% of the study group, with an average age of onset of symptoms of 23.3 years. The characteristics of migraine noted revealed certain rare factors aggravating headache. A positive family history of headache was observed in 24.7% of probands with a possible maternal inheritance on clinical grounds in 29 of 41 families (70.7%). CONCLUSIONS: This is an observational study from an Indian centre on the clinical characteristics of migraineurs in India. It revealed that migraineurs presented a relatively low frequency of family history of headache. Though a definite pattern of inheritance can't be commented on, majority with a positive family history of headache had a trend to possible maternal inheritance.