Epilepsy is a common neurological disorder whose consequences are influenced socially and culturally, especially in India. This review (second of the two part series) was carried out to understand the social impact and economic burden to develop comprehensive program for control and prevention of epilepsy. Epilepsy is known to have adverse effect on education, employment, marriage, and other essential social opportunities. Economic burden associated with epilepsy is very high with treatment and travel costs emerging as an important contributing factor. A vicious cycle between economic burden and poor disease outcome is clear. There is no significant change in the perception, stigma, and discrimination of epilepsy across the country despite improvement in educational and social parameters over the time. The huge treatment gap and poor quality of life is further worsened by the associated comorbidities and conditions. Thus, a multidisciplinary response is needed to address the burden and impact of epilepsy which calls for an integrated and multipronged approach for epilepsy care, prevention, and rehabilitation. Service delivery, capacity building, integration into the existing program, mobilizing public support, and increasing public awareness will be the hallmarks of such an integrated approach in a public health model.

Nanotechnology is a promising, novel field of technological development. There is great potential in research and clinical applications for neurological diseases. Here we chronicle the inception of nanotechnology, discuss its integration with neurology, and highlight the challenges in current application. Some of the problems involving practical use of neuronanotechnology are direct biological toxicity, visualization of the nanodevice, and the short life expectancy of nanomachinery. Neuron cell therapy is an upcoming field for the treatment of challenging problems in neurology. Peptide nanofibers based on amphiphilic molecules have been developed that can autoregulate their structure depending on the conditions of the surrounding milieu. Such frameworks are promising for serving as drug delivery systems or communication bridges between damaged neurons. For common disabling diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), recent developments have seen revolutionary nanotech-based novelties, which are discussed here in detail. Bioimaging integrated with nanoneuromedicine has opened up new doors for cancer and infection therapeutics.

Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality.

Background: Anatomy of circle of Willis (CW) shows wide variation in different individuals, population groups, and has vital clinical significance in causation and presentation of clinical disease. This study evaluates the anatomical variations, incidence of various common anomalies of CW in south Indian tertiary hospital set up, using three-dimensional time-of-flight (3D-TOF) magnetic resonance angiography (MRA). Materials and Methods: A total of 300 patients referred for neuroimaging study over a period of 2-year were included in the analysis. In this prospective and retrospective study, 198 men and 102 women; mean age, 55 years) underwent 3D-TOF MR angiograms of the CW using a 1.5-tesla MR scanner. Images were reviewed for anatomical configuration of the CW using maximum intensity projection (MIP) and 3D volume rendered images. Results: On analysis, a complete CW was seen in 50 (16.6%) of 300 subjects. An incomplete anterior and posterior CW was found in 66 (22%) The remaining 184 (61.3%) subjects had partially complete CW configuration. The most common type of CW in a single subject was anterior variant type A and posterior type variant E. Conclusion: We observed wide variation in CW configuration in our patients. The prevalence of complete configuration of the circle is 16.6%; slightly higher in females and younger subjects. Complete anterior circle was present in 77.3%. Most common anterior variant is type A (normal anterior configuration) with a prevalence of 66%. The most common posterior circle variant is type E (hypoplasia or absence of both PcomA) with 32.6%. Overall, CW variants are slightly more common among the women in comparison to men. Incidence of associated anomalies like aneurysm or arteriovenous malformation (AVM) was comparable to that described in literature.

Introduction: Past few decades have seen an increasing application of techniques like electron microscopy, western blotting, and molecular genetics in the evaluation of muscle diseases. However, due to their limited availability, histopathological interpretation of muscle biopsies still remains an important component of diagnostic approach to muscle diseases. A systematic methodology is required in the evaluation and interpretation of muscle biopsies. This study was undertaken to analyze the histopathological spectrum of 164 muscle biopsies and to assess the diagnostic yield of basic histopathological procedures in the work up of muscle biopsy. Materials and Methods: Retrospective analysis was done for 164 cases of muscle biopsies. Step-wise approach was adopted to assess the efficacy of routine stains, enzyme histochemistry, and immunohistochemistry. Based on hematoxylin and rosin (H and E) appearance, biopsies were broadly categorized into destructive, nondestructive but myopathic, and inflammatory morphology. Role of special stains, enzyme, and immunohistochemical stains in each category was then evaluated. Results: On the basis of histopathological features, 164 muscle biopsies were broadly categorized into biopsies with abnormal histopathological features (115) and biopsies with normal histopathology (49). Abnormal muscle biopsies were further categorized into destructive morphology (56.5%), nondestructive but myopathic morphology (30.5%), and inflammatory pathology (13%). A near definitive diagnosis could be made in 115 cases out of 164 muscle biopsies on the basis of routine histopathology, enzyme histochemistry, and immunohistochemistry. Conclusion: Though advanced techniques like electron microscopy, western blotting, and molecular genetics are essential for confirmatory diagnosis, a substantive diagnostic yield can be offered with the basic armamentarium of routine (frozen) stains, enzyme histochemistry, and immunohistochemistry.

Objectives: The aim of this study was to assess the effect of sodium valproic acid (SVA) on the sleep quality of patients with juvenile myoclonic epilepsy (JME). Materials and Methods: Standardized sleep questionnaires viz. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were administered to 30 drug-naïve patients with JME (male:female (M:F) = 14:16; age: 21 ± 3.7 years) and the changes following SVA monotherapy was analyzed using t- and chi-squared tests. Results: The mean age at onset of seizures and diagnosis was 15.43 ± 3.8 and 21 ± 5.1, years respectively. All had myoclonic jerks with mean duration of 5.23 ± 2.7 years, aggravated by sleep deprivation (23, 76.7%) and sleep-wake transition (29, 96.7%). Twenty-seven (90%) had generalized tonic-clonic seizures (GTCS), majority (70%) on awakening from sleep. Seizures were controlled in 25 patients (83.33%) with SVA monotherapy. Abnormal ESS was noted in five (16.66%) drug naοve patients compared to six (20%) patients while on SVA (P = 0.782). Mean ESS remained unchanged before and after SVA therapy (6.27 ± 4.4 vs 6.97 ± 4.7, P = 0.262). On the other hand, only four (13.3%) patients had abnormal PSQI scores at follow-up after initiation of SVA, as compared to 14 (46.7%) subjects in the drug naïve state (P = 0.037). Further, we also found significant reduction in mean PSQI scores after initiating SVA monotherapy (6.7 ± 5.6 vs 2.7 ± 2.84, P ͳ 0.0001). Conclusion: This study showed that the mean PSQI as well as the number of patients with abnormal PSQI significantly reduced after initiating SVA therapy, suggesting a significant improvement in night-time sleep quality with SVA treatment. However, SVA therapy did not alter ESS.

Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India. Materials and Methods: Patients who fulfilled modified Zuliani et al.'s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.

Introduction: Carotid stenosis is a major risk factor for ischemic stroke. However, the effect of carotid stenosis on the site of stroke is still under investigation. Aims: This study aimed to elucidate how the presence of carotid stenosis influenced the pattern of stroke and also how it interacted with other risk factors for stroke. Materials and Methods: Thirty-eight patients with ischemic stroke were included in this study and were investigated with carotid artery Doppler and magnetic resonance angiography for carotid stenosis and intracranial stenosis in the circle of Willis, respectively. Other known risk factors of stroke were also studied in and compared between the subgroups with and without carotid stenosis. Results: In patients without carotid stenosis, anterior cerebral artery was the commonest site of stenosis. In patients with carotid stenosis, middle cerebral artery was the commonest site of stenosis. Overall, middle cerebral artery was the commonest territory of stroke. Patients with hypertension, diabetes and history of smoking had preferential stenosis of the anterior cerebral artery.

Background: Acute management of ischemic stroke involves thrombolysis within 4.5 h. For a successful outcome, early recognition of stroke, transportation to the hospital emergency department immediately after stroke, timely imaging, proper diagnosis, and thrombolysis within 4.5 h is of paramount importance. Aim: To analyze the obstacles for thrombolysis in acute stroke patients. Materials and Methods: The study was conducted in a tertiary care center in South India. A total of hundred consecutive patients of acute ischemic stroke who were not thrombolysed, but otherwise fulfilled the criteria for thrombolysis were evaluated prospectively for various factors that prevented thrombolysis. The constraints to thrombolysis were categorized into: i) Failure of patient to recognize stroke symptoms, ii) patient's awareness of thrombolysis as a treatment modality for stroke, iii) failure of patient's relative to recognize stroke, iv) failure of primary care physician to recognize stroke, v) transport delays, vi) lack of neuroimaging and thrombolysis facility, and vii) nonaffordability. Results: The biggest hurdle for early hospital presentation is failure of patients to recognize stroke (73%), followed by lack of neuroimaging facility (58%), nonaffordability (56%), failure of patient's relative to recognize stroke (38%), failure of the primary care physician to recognize stroke (21%), and transport problems (13%). Awareness of thrombolysis as a treatment modality for stroke was seen only in 2%. Conclusion: Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for improvement to overcome various hurdles that prevent thrombolysis.

Background: We, as neurologists, are frequently consulted to give neurological clearance for surgery in patients who are undergoing coronary artery bypass graft (CABG) surgery and have suffered from stroke or transient ischemic attack (TIA) in past. Similarly clearance is also sought in another group of patients who, though have not suffered from stroke or TIA, but found to have significant carotid stenosis on routine screening prior to surgery. Cardiac surgeons and anesthetists want to know the risk of perioperative stroke in such patients and should carotid endarterectomy (CEA) be done along with CABG. In absence of any clear-cut guideline, neurologists often fail to give any specific recommendation. Aim: To find out safety and efficacy of synchronous CEA in patients undergoing CABG. Design: Retrospective study. Materials and Methods: Out of 3,700 patients who underwent CABG, 150 were found to have severe carotid stenosis of >70%. Out of this, 46 patients with >80% stenosis (three symptomatic and 43 asymptomatic) and one patient with >70% symptomatic carotid stenosis (TIA within last 2 weeks) were taken for simultaneous CEA along with CABG. These three symptomatic carotid patients had suffered from stroke within last 6 months. Results: One patient with asymptomatic near total occlusion of carotid artery suffered from hyperperfusion syndrome. None suffered from ischemic stroke, myocardial infarction (MI), or death during perioperative period. Conclusion: Combining CEA along with CABG is a safe and effective procedure.

Context: With advances in neuroimaging, traditional views regarding the clinicoanatomic correlation in stroke patients with aphasia are being challenged and it has been observed that lesions at a given cortical or subcortical site may manifest with different aphasia profiles. Aims: To study as to whether there is a strict clinicoanatomical correlation between the type of aphasia and lesion site in patients with first ever stroke. Settings and Design: Observational study, based in a tertiary care center. Materials and Methods: Stroke patient's ≥18 years of age were screened and those with first ever stroke and aphasia were subjected to a detailed stroke workup and language assessment using the Hindi version of Western Aphasia Battery (WAB). Statistical analysis was done with χ² test with Yates correction and Kruskal-Wallis test. The level of significance was set at P < 0.05. Results: Overall aphasia was detected in 27.9% of the 260 screened cases with stroke. Amongst 60 cases with first ever stroke and aphasia, the aphasia type was: Global (33.33%), Broca's (28.3%), transcortical motor (13.33%), transcortical sensory (10%), Wernicke's (8.33%), anomic (5%), and conduction (1.67%) aphasia. A definite correlation between the lesion site and the type of aphasia as per the traditional classification was observed in 35% cases only. Conclusions: No absolute correlation exists between the lesion site and the type of clinical aphasia syndrome in majority of the patients with cortical and subcortical stroke.

Background: Carotid intima-media thickness (IMT) is increasingly identified as a marker of atherosclerosis and increased risk of cerebrovascular disease. Aim: We aimed to investigate the prevalence of carotid IMT in asymptomatic Indian individuals, more than 40 years of age, and correlate it with other risk factors for cerebrovascular ischemia. Materials and Methods: Individuals attending outpatient services of Nizam's Institute of Medical Sciences, who were asymptomatic for cerebrovascular ischemia underwent detailed history and carotid Doppler examination. IMT on mid common carotid artery (CCA) was measured. All subjects' blood was taken for biochemical estimation of fasting blood sugar and total cholesterol levels. Results: Out of 1,392 subjects, 571 (41%) had abnormal IMT and 821 (59%) had normal IMT. On comparison of the two groups, the factors significantly associated with abnormal IMT were mean older age (59 vs 50.7 years; P < 0.0001) and higher prevalence of hypertension (257 (45%) vs 236 (28.7%); P < 0.0001), diabetes (159 (27.8%) vs 139 (16.9%); P < 0.0001), and hypercholesterolemia (124 (21.7%) vs113 (13.7%); P = 0.0001). After adjustment with multiple logistic regression, significant predictors were age (odds 3.2; 95% confidence interval (CI) 2.5-4.1), male gender (odds 1.5; 95% CI 1.1-1.9), hypercholesterolemia (odds 1.5; 95% CI 1.1-2.0), hypertension (odds 1.4; 95% CI 1.1-1.8), and diabetes (odds 1.3; 95% CI 1.0-1.7). Conclusion: We found age, sex, hypertension, diabetes, and hypercholesterolemia to be independent risk factor for abnormal IMT in asymptomatic subjects over 40 years of age.

Background: Sparse published data are available regarding the prognostic importance of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute ischemic stroke. Materials and Methods: We prospectively studied 74 consecutive patients presenting with acute ischemic stroke within 24 hours of onset. All of them underwent laboratory and imaging evaluation and were treated as per guidelines. In all subjects, plasma NT-proBNP levels were measured at initial admission and again on day 7. Results: Their mean age was 54 ± 13.5years; there were 49 males; 18 (24%) patients died during the hospital stay. A statistically significant negative correlation between log NT-proBNP and Glasgow coma scale (GCS) score (P < 0.001); and a significant positive correlation between log NT-proBNP and National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) were observed. Baseline log NT-proBNP levels were higher among non-survivors compared with survivors (6.7 ± 0.47 vs. 5.37 ± 0.62; P = 0.06); day 7 log NT-proBNP levels were significantly higher in non-survivors compared with survivors (7.3 ± 0.26 vs. 4.5 ± 0.4; P = 0.000). In survivors, there was a statistically significant decline in log NT-proBNP levels from baseline to day 7 (5.3710 ± 0.620 vs. 4.5320 ± 0.451; P < 0.001). In contrast, among non-survivors, log NT-proBNP levels showed a statistically significant increase from baseline to day 7 (4.5322 ± 0.451 vs. 7.2992 ± 0.263; P < 0.001). On receiver operator characteristic curve (ROC) analysis, at a cut-off value of ≥ 6.0661, log NT-proBNP had a sensitivity and specificity of 98.2 and 88.9, respectively, in predicting death. Conclusions: Plasma log NT-pro-BNP level appears to be a useful biological marker for predicting in-hospital mortality inpatients presenting with acute ischemic stroke.

Background: Aphasia, an acquired inability to understand and/or speak language, is a common repercussion of stroke that denigrates the quality of life (QOL) in the affected persons. Several languages in India experience the dearth of instruments to measure the QOL of persons with aphasia. Malayalam, the language spoken by more than 33 million people in Kerala, the southern state of India, is not an exception to this. Objective: This study aimed to adapt and validate the widely-used stroke-aphasia quality of life (SAQOL-39) scale to Malayalam. Materials and Methods: We required seven Malayalam-speaking Speech Language Pathologists (SLPs), hailing from different regions of Kerala, to examine the socio-cultural suitability of the original items in SAQOL-39 and indicate modifications, wherever necessary. Subsequently, the linguistic adaptation was performed through a forward-backward translation scheme. The socio-culturally and linguistically adapted Malayalam version was then administered on a group of 48 Malayalam-speaking persons with aphasia to examine the test-retest reliability, acceptability, as well as the internal consistency of the instrument. Results: The Malayalam SAQOL-39 scale showed high test-retest reliability (intraclass correlation coefficient, ICC = 0.91) as well as acceptability with minimal missing data (0.52%). Further, it yielded high internal consistency (Chronbach's ∝ = 0.98) as well as item-to-total and inter-domain correlations. Conclusions: The Malayalam version of SAQOL-39 is the first socio-culturally and linguistically adapted tool to measure the QOL of persons with stroke-aphasia speaking this language. It may serve as a potential tool to measure the QOL of this population in both clinical practice and future research endeavors.

Tangier disease is a rare metabolic disorder that causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle-aged gentleman of Tangier disease who was initially diagnosed as leprosy and treated with antileprosy drugs. The presence of a demyelinating electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.

Painful leg and moving toes (PLMT) syndrome is a distinct clinical entity and in majority of the patients there are some underlying causes related to spinal cord, cauda equina, or peripheral neuropathy. However, some cases are cryptogenic with no identifiable underlying cause. Response to treatment is disappointing in most of the cases. We report a 60-year-old lady who presented with very severe type of painful legs and moving toes (PLMT) with no underlying cause.

Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS), which is disabling and majorly involves younger population. Various available treatments in forms of immunomodulation are not very effective; however, stem cell transplantation seems to be promising in recent literature. The current case report is a novel evidence for autologous hematopoietic stem cell transplantation (HSCT) in progressive MS. Case Summary: A 33 year old male with secondary progressive MS (SPMS), after being failed and/or intolerance to standard approved interferon (IFN) and mitoxantrone therapy, autologous HSCT was administered. At 2years of post-stem cell transplantation follow-up, he has remained stable with some improvement in functional status (Expanded Disability Status Scale (EDSS) reduced by 1.5), with no relapse, no treatment related complications, and no fresh magnetic resonance imaging (MRI) lesions. Conclusion: Autologous stem cell transplantation may be beneficial in progressive forms of MS, but needs to be tested in well-designed randomized trial.

A 18-year-old male, screen printer by profession developed sensory motor polyneuropathy, change in his behavior, bilateral 6 ^th and 7 ^th cranial nerve palsies, down beat nystagmus and cerebellar dysarthria. He had bilaterally prolonged P100 latency; left: 137 ms; right: 144 ms. P 37 was not recordable on either side while N 20 was normal. The inter latency difference between Ipsilateral R2 and Contralateral R2 was 6.15 ms, on the left side and normal on the right side. In the follow-up, there was normalization of the blink reflex study, improvement in P100 latency [left: 114 ms; right: 120 ms.] but worsening of peripheral nerve conductions. The sequential clinical recovery was of the behavioral dysfunction, down beat nystagmus, 6 ^th nerve, 7 ^th nerve involvement and ataxia, in that order. Sural nerve biopsy showed loss of large diameter myelinated fibers.

Idiopathic intracranial hypertension (IIH) is a disorder defined by clinical criteria that include signs and symptoms isolated to those produced by increased intracranial pressure (ICP; e. g., headache, papilledema, and vision loss), elevated ICP with normal cerebrospinal fluid (CSF) composition, and no other cause of intracranial hypertension evident on neuroimaging or other evaluations. The most common signs in IIH are papilledema, visual field loss, and unilateral or bilateral sixth cranial nerve palsy. Here we report a case of IIH presenting as headache with vision loss, papilledema, complete ophthalmoplegia with proptosis in one eye, and sixth cranial nerve palsy in the other eye. Patient was managed with acetazolamide, topiramate, and diuretics. Symptoms remained static and she was planned for urgent CSF diversion procedure.

Fucosidosis is a rare lysosomal storage disease with clinical presentation of developmental retardation, coarse facial features, hepatosplenomegaly, dysostosis multiplex, and angiokeratomas. Here, a 7-year-old female patient with progressive dystonic movement disorder and loss of acquired motor skills is presented. Coarse facial feature and abnormal globuspallidus signaling in brain magnetic resonance imaging (MRI) led the patient to be investigated in terms of fucosidosis despite absence of hepatosplenomegaly, dysostosis multiplex, and angiokeratomas. Markedly decreased enzyme activity of alpha-fucosidosis led to the correct diagnosis. Conclusion: Various neurological findings have recently been reported in fucosidosis. However, neuroimaging findings have not been studied in detail except a few studies. It is critically important to discuss the wide neuroradiological spectrum of the disease and to highlight fucosidosis in differential diagnosis of bilateral pallidalhypointensity on T2-weighted images in brain MRI. In addition, description of atypical clinical findings of fucosidosis should avoid clinicians from diagnostic delay.

Benign intracranial hypertension is characterized with increase in CSF opening pressure with no specific etiology. It is predominantly found in women of child bearing age and particularly in individuals with obesity. Visual disturbances or loss and associated headaches are common and can lead to blindness if left untreated. Diagnosis can be achieved once other causes of visual loss, headaches and high opening pressures are excluded. Management consists of serial optic disc assessments although no specific treatment is available despite recent trials using carbonic anhydrase inhibitors. Diet modification and weight management can help in therapy.