Annals of Indian Academy of Neurology

This article is intended to give the reader guidance in evaluating different study designs used in medical research for better scientific quality, reliability and validity of their research. This article explains three main types of study designs with understanding examples. Care and caution with skills and experience needed to design suitable studies and appropriate design coupled with reliable sampling techniques and appropriate statistical analysis, supported by clear objectives with decent communication of the findings, are essential for good research.

To assess the surgical outcome of myasthenia gravis (MG) following thymectomy and to determine the outcome predictors to such therapeutic approach. This study is a retrospective review of 80 consecutive thymectomies performed for MG over a 16-year period. There were 41 females and 39 males (mean age, 34.32 years) with mean disease duration of 17.45 months prior to surgery. Stagewise distribution of the patients revealed 2.5% in stage I, 48.7% in stage IIA, 33.8% in stage IIB, 8.7% in stage III, and 6.3% in stage IV. The surgical approach was either trans-sternal (n=67) or video-assisted thoracoscopic route (n=13). Follow-up was obtained in 91.2% (n=73) of patients with mean duration of 67.7 months. At their last follow-up, 26.0% were in complete remission, 35.6% were asymptomatic on decreased medications, and 17.8% had clinical improvement on decreased medications. Overall, 79.4% of patients benefited from surgery, 8.2% had unchanged disease status, and 12.3% worsened clinically. Factors influencing favorable outcome include sex, disease stage, gland weight, and preoperative medication with anti-cholinesterase (P<0.05). There was one death in the perioperative period due to septicemia. Two patients died at fourth and seventh month following thymectomy. Thymectomy for MG is safe and effective. Certain influencing factors may shape treatment decisions and target higher risk patients.

Spinocerebellar ataxia 17 (SCA17) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cerebellar ataxia in combination with variable neurological symptoms. Here we report a Chinese SCA17 family which proband's clinical manifestation was inconsistent with the neuroimage findings.

After malaria, schistosomiasis is the second most prevalent tropical disease. The prevalence of oviposition in CNS of infected persons varies from 0.3 to 30%. The conus medullaris is a primary site of schistosomiasis, either granulomatous or acute necrotizing myelitis. To report the clinical, radiological, and laboratory results of spinal cord schistosomiasis (SCS) and to design proper therapeutic regimens. Seventeen patients (13 males and four females) with SCS were enrolled between 1994 and 2009 at Mansoura University Hospitals. Their median age at diagnosis was 19 years (13-30 years). Independent neurological, radiological, and laboratory assessments were performed for both groups, excluding pathological confirmation that was done earlier in eight patients (Group 1). In the group 2 (nine patients), indirect hemagglutination (IHA) test for bilharziasis in blood and cerebrospinal fluid (CSF) was performed. Higher positive titer in CSF than serum indicated SCS plus induction of antibilharzial and corticosteroid protocols for 12 months with a three-year follow-up. Rate of neurological symptoms of granulomatous intramedullary cord lesion was assessed independently in 16 cases and acute paraparesis in one case. All patients in group 2 had positive IHA against Schistosoma mansoni with median CSF and serum ranges 1/640 and 1/320, respectively. Seven patients (41.18%) had complete recovery, eight patients (47.06%) showed partial recovery, and no response was reported in two patients (11.76%) (P = 0.005). There was no recorded mortality in the current registry. Rapid diagnosis of SCS with early medical therapies for 12 months is a crucial tool to complete recovery.

18-Fluoro-2-deoxy-D-glucose(FDG) is a structural analog of 2-deoxyglucose and accumulates in malignant tissues but also at sites of infection and inflammation. For this reason, FDG PET or PET/CT has great advantage in understanding of underlying pathology in assessment of FUO (Fever of unknown origin). However, till today, there are limited studies about the role of FDG PET or PET/CT in evaluation of FUO. Conventional diagnostic methods are still not adequate to reveal underlying reason in approximately 50% of patients with FUO especially in cases presenting with diagnostic challenges i.e. involvement of two or more organ systems with seemingly no correlation. We report a case of two years old Indian female child who presented with fever of one month duration, CT and MRI reported nonspecific findings. She underwent Whole body 18 FDG PET/CT for further evaluation, which revealed FDG avid rim lesion with central photopenic defect suspicious of pyogenic abscess in high parietal cortex along with bilateral lung nodules. This confirmed the diagnosis of a brain abscess secondary to pulmonary infection. We emphasize the utility of 18 FDG PET/CT as imaging modality, highlight the diagnostic difficulties using current serological and radiological measures, and propose managing FUO with 18 FDG PET/CT in cases empirically prior to more invasive measures.

Nearly 80% of the 50 million people with epilepsy worldwide reside in developing countries that are least equipped to tackle the enormous medical, social and economic challenges posed by epilepsy. These include widespread poverty, illiteracy, inefficient and unevenly distributed health care systems, and social stigma and misconceptions associated with epilepsy. Several studies have reported that a large proportion of patients with epilepsy in developing countries never receive appropriate treatment for their condition, and many, though diagnosed and initiated on treatment, soon discontinue treatment. Unaffordable cost of treatment, unavailability of antiepileptic drugs, and superstitious and cultural beliefs contribute to high epilepsy treatment gap in resource-poor countries. A significant proportion of the current burden of epilepsy in developing countries can be minimized by educating the public about the positive aspects of life with epilepsy and the primary and secondary physicians about current trends in the management of epilepsies, scaling up routine availability of low-cost antiepileptic drugs, and developing cost-effective epilepsy surgery programs.

Neuromyelitis optica is an inflammatory demyelinating disorder of the central nervous system. The discovery of a specific antibody (NMO IgG /aquaporin-4 antibody) in patients with this condition has led to a marked revival of research on the disease. This article summarizes the major advances in neuromyelitis optica, particularly in the last 2 years, and supplements the previous review published in this Journal in 2007. Important among these developments are: the epidemiological studies, which have provided estimates of incidence and prevalence; identification of mutations in the aquaporin-4 gene; improved understanding of the effects of anti-aquaporin-4 antibody on astrocytes; roles of excitatory amino acid transporter type 2 and glutamate; requirement of aquaporin-4 to be in orthogonal arrays to be antigenic; recognition of the presence of aquaporin-4 antibody in patients with cancer and posterior reversible encephalopathy syndrome; possibility of monitoring the disease using the antibody, and the effectiveness of rituximab and mycophenolate in preventing relapses.

This study was designed to identify the indications for prescription of intravenous immunoglobulin (IVIg) in neurology and the cost effectiveness of this therapy. IVIg is a relatively costly therapy and the annual budget spent on providing this therapy for various indications at Ninewells Hospital was close to £1.5 million. In today's economic times, a cost-benefit analysis of all therapies is prudent. This is of relevance to countries in the developing world as well where perhaps not everybody could afford such cost-intensive therapy. We audited 2 time periods over 12 months each in 2004-2005 and 2008-2009 to look at the patterns of utilization of IVIg over these periods. We searched the literature for alternative and cost-effective therapies for the most common indications for use of IVIg. Fiscal costs on prescription of IVIg have rocketed up by almost 300% in this Neurology Department comparing data from 2004-2005 vs 2008-2009 and this is disproportionate to the increase in the annual admission rate (bed usage), partly because of the soaring costs of the drug available in the market and also because of the increased prescription of IVIg for numerous indications where clinical trials data are yet not so robust. We have looked at the cost of alternative therapies and offer some proposals that if implemented could potentially save £330,000 annually from the health budget at this NHS Trust. Perhaps similar models could evolve for better cost-effective utilization of IVIg in countries in the developing world where health budgeting is more acutely relevant.

Macroglossia is rare in patients of Duchenne muscular dystrophy (DMD), and its occurrence without any endocrinologic abnormality, seizures or an abnormal karyotype is even rarer. We describe a patient of DMD with isolated macroglossia with 271 bp deletion in exon 50 of the dystrophin gene and speculate a relationship in this regard.

Hypokalemic paralysis is characterized by episodes of acute muscle weakness associated with hypokalemia. In this study, we evaluated the possible etiological factors in patients of hypokalemic paralysis. We reviewed the records of 29 patients who were admitted with a diagnosis of hypokalemic paralysis. Modified Guillain-Barre´ Syndrome disability scale was used to grade the disability. In this study, 15 (51.7%) patients had secondary causes of hypokalemic paralysis and 14 patients (42.3%) had idiopathic hypokalemic paralysis. Thyrotoxicosis was present in six patients (20.6%), dengue infection in four patients (13.7%), distal renal tubular acidosis in three patients (10.3%), Gitelman syndrome in one patient (3.4%), and Conn's syndrome in one patient (3.4%). Preceding history of fever and rapid recovery was seen in dengue infection-induced hypokalemic paralysis. Approximately 62% patients had elevated serum creatinine phosphokinase. All patients had recovered completely following potassium supplementation. Patients with secondary causes were older in age, had significantly more disability, lower serum potassium levels, and took longer time to recover. In conclusion, more than half of patients had secondary causes responsible for hypokalemic paralysis. Dengue virus infection was the second leading cause of hypokalemic paralysis, after thyrotoxicosis. Presence of severe disability, severe hypokalemia, and a late disease onset suggested secondary hypokalemic paralysis.

Stroke is a major detriment to the quality of life (QOL) in its victims. Several functional limitations following stroke contribute to the denigrated QOL in this population. Aphasia, a disturbance in the comprehension, processing, and/or expression of language, is a common consequence of stroke. Yet, in most Indian languages, including the national language (Hindi), there are no published tools to measure the QOL of persons with stroke-aphasia. The current study was carried out to adapt and validate a well-known tool to measure the QOL (i.e., Stroke-Aphasia Quality of Life-39; SAQOL-39) to Hindi. We presented the original (English) version of the SAQOL-39 to a group of six Hindi-speaking Speech Language Pathologists hailing from the central and northern regions of India to examine the sociocultural suitability of items and indicate modifications, if any. The linguistic adaptation was performed through a forward-backward translation scheme. The socioculturally and linguistically adapted (to Hindi) version was then administered on a group of 84 Hindi-speaking persons with aphasia to examine the acceptability, test-retest reliability as well as the internal consistency of the instrument. The SAQOL-39 in Hindi exhibited high test-retest reliability (ICC = 0.9) as well as acceptability with minimal missing data. This instrument exhibited high internal consistency (Chronbach's ∝ = 0.98) as well as the both item-to-total and inter-domain correlations. The socioculturally and linguistically adapted Hindi version of SAQOL-39 is a robust tool to measure the QOL of persons with stroke-aphasia. It may serve as an essential tool to measure the QOL in this population for both clinical and research purposes.

Our present observational study attempted to evaluate the clinical profiles, diagnosis, treatment and follow-up results of 51 pediatric neurocysticercosis patients over a mean duration of five years (from January 2006 to December 2010). Diagnosis was mainly based on clinical features, computed tomography (CT)/magnetic resonance imaging scan and exclusion of other causes. Patients with active, transitional cysts and seizure were treated with albendazole for 28 days, steroids and anticonvulsants. A total of 38 patients completed this study. Mean age of the presentation was 8.47 ± 3.19 years 52.6% of the patients were female. Overall patients presented with generalized seizure in 55.3%, focal in 31.6%, headache ± vomiting in 63.2%, focal neurodeficit in 10.5% and combination of symptoms in 60.5% cases. Contrast CT brain showed a solitary lesion in 27 (71.1%) and multiple in the rest. At presentation lesions were transitional in 58.2%, inactive in 20% and mixed in 14.6%. After a mean of 2 years, seizure persisted in 9 (23.7%) and headache in 8 (21.1%) of whom six had normal electroencephalography (EEG) while one each showed focal slowing, generalized slowing and epileptiform discharges. During the follow-up, CT scan brain 44.7% lesions calcified, 31.6% disappeared, 10.5% regressed and the rest persisted. Solitary ring enhancing lesions (transitional stage) involving the parietal lobe was the commonest CT picture at presentation. Generalized tonic-clonic seizure was the most common type of seizure. Number of lesions, persistence of lesion, number of seizures, EEG abnormality at presentation were not found to be prognostically significant (P > 0.05).

Patients with restless leg syndrome present with sensory symptoms similar to peripheral neuropathy. While there is evidence of abnormalities of dopaminergic pathways, the peripheral nervous system has been studied infrequently. We studied conventional nerve conduction studies, quantitative thermal sensory testing and sympathetic skin response in 57 patients with primary restless leg syndrome. Almost two third patients demonstrated abnormalities in the detailed testing of the peripheral nervous system. Sbtle abnormalities of the peripheral nervous system may be more common than previously believed.

To evaluate clinical profile and short-term outcome of psychogenic non-epileptic seizures (PNES) in Indian adult population. A prospective observational study, conducted at tertiary teaching institute at New Delhi. Sixty-three patients with confirmed PNES were enrolled. The diagnosis was based on witnessing the event during video-electroencephalography (Video-EEG) monitoring. A detailed clinical evaluation was done including evaluation for coexistent anxiety or depressive disorders. Patients were divided into two groups on the basis of excessive or paucity of movements during PNES attacks. Patients were followed-up to 12 months for their PNES frequency. Means and standard deviations were calculated for continuous variables. Chi-square and Students t-test were used to compare categorical and continuous variables respectively. The mean age at onset of PNES was 25.44 years; with F:M ratio of 9.5:1. Coexistent epilepsy was present in 13 (20.63%) cases. Twenty-two patients (44%) with only PNES (n = 50) had received antiepileptic drugs. Out of 63 patients of PNES 24 (38.1%) had predominant motor phenomenon, whereas 39 (61.9%) had limp attacks. The common features observed were pre-ictal headache, ictal eye closure, jaw clenching, resistant behavior, ictal weeping, ictal vocalization, and unresponsiveness during episodes. Comorbid anxiety and depressive disorders was seen in 62.3% and 90.16% patients, respectively. Short-term (6-12 months) outcome of 45 patients was good (seizure freedom in 46.66% and >50% improvement in 24.44% cases). PNES is common, but frequently misdiagnosed and treated as epileptic seizures. A high index of suspicion is required for an early diagnosis. Proper disclosure of diagnosis and management of the psychiatric comorbidities can improve their outcome. Limited sample size and change in seizures frequency as the only parameter for the assessment of the outcome are the two major limitations of our study.

To study the electroclinical and histopathologic profile of idiopathic inflammatory myositis (IIM) with reference to prognosis and survival rate. Diagnosis of IIM was based on the Bohan and Peter criteria. Patients who improved and those whose condition worsened or who expired due to IIM per se at last follow-up were classified to have favorable and poor outcomes, respectively. Fisher's exact test was used for univariate analysis of prognostic factors. The study cohort consisted of consecutive 68 patients with IIM. The mean age at diagnosis was 36.5 years and females constituted 71%. Of these patients, 62% had definite IIM, 49% had polymyositis, 20% had dermatomyositis, and 29% had overlap syndrome. The mean follow-up period was 5.4 years. Prednisolone alone was used in 55 (80%), and azathioprine (1-3 mg/kg/day) alone in 12 (17.6%) as the initial treatment. Relapse of IIM with drug withdrawal was seen in 15 patients (22%); 70% had favorable outcome and 16% had expired. The treatment delay of ≤6 months (P = 0.001), absence of cardiac or lung involvement (P < 0.001), and positive biopsy (P = 0.033) were predictive of a favorable prognosis in the univariate analysis. In multivariate analysis, only the duration of illness of ≤6 months (P = 0.008) and the absence of cardiac or lung involvement (P = 0.001) predicted the favorable outcome at last follow-up. Cumulative survival rate was 95% at 1 year, 86% at the 5th year, and 80% at the 10th year. Approximately, two-thirds of the patients showed good electroclinical and histopathologic correlations and an equal number improved with treatment. The treatment delay (≥6 months), presence of cardiac or pulmonary involvements, and negative muscle biopsy are bad prognostic factors.

Hypertrophic pachymeningitis (HP) is a rare disorder of diverse etiology. It presents with headaches, cranial neuropathies and ataxia occurring alone or in combination. Dural biopsy is essential to exclude secondary causes of pachymeningitis. There is paucity of data on biopsied cases of HP. We report three biopsy-proven cases of idiopathic hypertrophic cranial pachymeningitis. All our patients had headaches and multiple cranial neuropathies; ataxia was seen in one patient. One patient had recurrent anterior and posterior cranial neuropathies, while one each had recurrent anterior and posterior cranial neuropathies. Two patients had profound irreversible mono-ocular visual loss. All of them showed prominent pachymeningeal thickening on imaging. Infarcts were seen in one patient, which have rarely been documented. All patients showed biopsy evidence of meningeal thickening and nonspecific chronic inflammation of the dura. The disease may have a remitting and relapsing course, and usually responds to steroids. Clinical improvement was excellent in two patients and modest in one on steroid therapy. All our patients required azathioprine during the course of therapy. Early institution and long-term maintenance of steroid therapy prevents neurologic sequelae. Occurrence of abdominal inflammatory pseudotumor in a patient of HP possibly as part of multifocal fibrosclerosis has not been described earlier.

Abetalipoproteinemia is an uncommon cause of ataxia and retinitis pigmentosa (RP). Most of the neurological and ocular manifestations occur secondary to deficiency syndromes that is consequent to fat malabsorption from the small intestine. In this report, we have described the phenotype of a young adult female who manifested with recurrent diarrheal illness in her first decade, followed by anemia, RP, and neurological involvement with progressive deafness, cerebellar and sensory ataxia, and subclinical neuropathy in her second decade of life. While RP and sensory ataxia due to vitamin E deficiency are well-recognized features of abetalipoproteinemia, deafness is rarely described. In addition, we have highlighted the abnormal posterior column signal changes in the cervical cord in this patient. Early recognition avoids unnecessary investigations and has a potential to retard the disease progression by replacing some of the deficient vitamins.

Anti N Methyl D Aspartate receptor immune encephalitis (Anti NMDARE) is a recently defined, under-recognized and often misdiagnosed disease, which typically occurs in young females and may be associated with an underlying tumor, usually ovarian teratoma. If diagnosed early, initiation of immunotherapy and tumor removal (if present) may result in recovery. We report a case of a 17 years old girl with Anti NMDARE who was initially misdiagnosed as Functional psychosis, Neuroleptic Malignant Syndrome and Sepsis syndrome. To the best of our knowledge, this is only the second case of anti NMDARE being reported from India. This case report underscores the need for a greater awareness of this entity across multiple specialties, e.g., general medicine, psychiatry and neurology, to ensure a heightened diagnostic suspicion, which can lead to timely diagnosis and adequate therapy of this treatable disease.

Electrocardiographic (ECG) changes are reported frequently after acute strokes. It seems that cardiovascular effects of strokes are modulated by concomitant or pre-existent cardiac diseases, and are also related to the type of cerebrovascular disease and its localization. We aimed to determine the pattern of ECG changes associated with pathophysiologic categories of acute stroke among patients with/without cardiovascular disease and to determine if specific ECG changes are related to the location of the lesion. The electrocardiographic records of 361 patients with acute stroke were studied to assess the relative frequencies of ECG abnormalities among the pathophysiologic categories of stroke. In the present study, the most common ECG abnormalities associated with stroke were T-wave abnormalities, prolonged QTc interval and arrhythmias, which were respectively found in 39.9%, 32.4%, and 27.1% of the stroke patients and 28.9%, 30.7%, and 16.2 of the patients with no primary cardiac disease. We observed that other ECG changes comprising pathologic Q- wave, ST-segment depression, ST-segment elevation, and prominent U wave may also occur in selected or non-selected stroke patients; thereby simulate an acute myocardial injury. We observed an increased number of patients with abnormal T-wave and posterior fossa bleedings and more rhythm disturbances for ischemic lesions, localized in the anterior fossa. Ischemia-like ECG changes and arrhythmias are frequently seen in stroke patients, even in those with no history or signs of primary heart disease, which support a central nervous system origin of these ECG abnormalities. Further study is necessary to better define the brain-heart interaction.

Compound muscle action potential (CMAP) amplitude declines during a paralytic attack in patients with hypokalemic periodic paralysis (HPP). However, serial motor nerve conduction studies in hypokalemic paralysis have not been commonly reported. We report two cases with hypokalemic paralysis, who had severely reduced CMAPs in all motor nerves at presentation during the episode of quadriparesis. However, the amplitude of CMAPs increased and reached normal levels, as the serum potassium concentration and motor power returned to normal state.

Hyperkalemia manifests clinically with acute neuromuscular paralysis, which can simulate Guillain Barré syndrome (GBS) and other causes of acute flaccid paralysis. Primary hyperkalemic paralysis occurs from genetic defects in the sodium channel, and secondary hyperkalemic paralysis (SHP) from diverse causes including renal dysfunction, potassium retaining drugs, Addison's disease, etc. Clinical characteristics of SHP have been addressed in a number of publications. However, electrophysiological evaluations of these patients during neuromuscular paralysis are infrequently reported and have demonstrated features of demyelination. The clinical features and electrophysiological abnormalities in secondary hyperkalemia mimic GBS, and pose diagnostic challenges. We report the findings of nerve conduction studies in a middle-aged man who was admitted with rapidly reversible acute quadriplegia resulting from secondary hyperkalemic paralysis.

Fungi are a relatively uncommon cause of brain abscess in neonates and early infancy. They are usually associated with predisposing factors like prematurity, low birth weight, use of broad-spectrum antibiotics, and prolonged stay in the intensive care unit. Candida tropicalis (C. tropicalis) is rapidly emerging as a nosocomial threat in the neonatal intensive care settings. This case report describes a neonate with C. tropicalis brain abscess who was diagnosed early and managed aggressively with a favorable outcome. Inadvertent use of intravenous antibiotics can have serious complications such as invasive fungal infection. Correct microbiological diagnosis is the key to successful treatment of deep-seated pyogenic infection. Fungal etiology should always be studied in relevant clinical settings.

Mycobacterial opportunistic infections are a major cause of morbidity and mortality among patients living with HIV (PLHIV) worldwide. Nontuberculous mycobacterial (NTM) infection is one of the leading causes of opportunistic infection in patients with advanced acquired immunodeficiency syndrome i.e., with CD4 count less than 50/cu.mm. Mycobacterium avium complex (MAC) is among the most common opportunistic bacterial infections in those patients with advanced immunodeficiency apart from cryptococcal meningitis, progressive multifocal leukoencephalopathy, etc. Common presentations of mycobacterium avium complex are fever, lymphadenitis and respiratory disease. Immune reconstitution disease is also known to manifest with MAC infections in PLHIV on highly active antiretroviral therapy. Very few cases of central nervous system involvement due to NTM infection have been described. We are reporting a case of advanced acquired immunodeficiency who presented with brain abscess due to Mycobacterium avium intracellulare.

Tuberculous brain abscess and subdural empyema are extremely rare manifestations of central nervous system tuberculosis. Here, we report a case of an 11-year-old immunocompetent child who developed temporal lobe abscess and subdural empyema following chronic otitis media. A right temporal craniotomy was performed and the abscess was excised. The Ziehl Nielsen staining of the aspirated pus from the temporal lobe abscess yielded acid fast bacilli. Prompt administration of antituberculous treatment resulted in complete recovery of the child. Even though the subdural abscess was not drained, we presume that to be of tubercular aetiology. Ours is probably the first case of brain abscess and subdural empyema due to Mycobacterium tuberculosis reported in the same child. This case is being reported because of its rarity and to stress the importance of routine staining for tubercle bacilli in all cases of brain abscess, especially in endemic areas, as it is difficult to differentiate tuberculous from pyogenic abscess clinically as well as histopathologically.

Report of a case of young immunocompetent male adult with autopsy proven acanthamoeba meningoencephalitis. The patient presented with a protracted febrile illness of 3 months duration with features of meningoencephalitis, this was followed by rapid deterioration while on anti tuberculous therapy and steroids and ended fatally. His magnetic resonance imaging showed features of hemorrhagic meningoencephalitis and magnetic resonance spectroscopy showed choline peak. Autopsy revealed necrotizing meningoencephalitis and intraocular colonization due to acanthamoeba.

Acquired myasthenia Gravis (MG), a disorder of impaired neuromuscular transmission is recognized as an autoimmune disorder, with a majority of the patients having antibodies against acetylcholine receptor (AChR antibodies) in the serum. To correlate the AChR antibody status with the clinical characteristics of patients with myasthenia gravis. Retrospective and prospective study. This study was carried out in patients with definite MG, attending the Neurology services of the National Institute of Mental Health and Neurosciences, Bangalore, India, during the period 1999-2003. The AChR antibody status was determined using the direct and indirect enzyme linked immunosorbent assay (ELISA) technique. There were 165 patients in this study (M : F :: 1.5 : 1). The overall seropositivity rate was 59.4%. Seropositive patients had higher age of onset and presentation, and more frequent occurrence of crises, both at presentation and at any time during the course. Other parameters, viz. gender of the patient, Osserman staging, thymic enlargement on CT and remission during follow-up did not differ between the two groups. This communication reports the result of AChR antibody assay in a large cohort of patients, using a simple diagnostic tool, namely direct and indirect ELISA technique. In addition, the characteristics of a large cohort of patients with seronegative myasthenia gravis are described.

Glutaric aciduria Type-I (GA-I) has characteristic clinical and neuroimaging features, which clinches the diagnosis in a majority of patients. However, there have been few case reports on GA-I from India. This study was undertaken to study the clinical presentations, metabolic profile, neuroimaging findings and outcome of patients with GA-I. The present study was a retrospective study. Retrospective review of charts of patients with a diagnosis of GA-I was carried out from March 2008 to April 2010. The clinical, laboratory and neuroimaging findings were extracted in a predesigned proforma and the data was analyzed. Eleven cases were found to have GA-1. Clinical presentation was quite varied. Follow-up of patients revealed that one patient with macrocephaly as the only clinical finding was developmentally normal. One patient with encephalitis-like illness steadily improved and started walking at 2 years. Two patients were bed ridden and had severe dystonia. One patient died during follow-up. The remaining six patients had dystonia and other abnormal movements, but had attained sitting without support and were not ambulatory. GA-I is not an uncommon disorder and diagnosis can be made easily based on clinical, laboratory investigations and neuroimaging findings. It is one of the treatable metabolic disorders and, if managed appropriately, favorable prognosis can be given.

L-2-hydroxyglutaric aciduria (L-2-HGA), a neurometabolic disorder caused by mutations in the L-2 hydroxyglutarate dehydrogenase (L-2-HGDH) gene, presents with psychomotor retardation, cerebellar ataxia, extrapyramidal symptoms, macrocephaly and seizures. Characteristic magnetic resonance imaging findings include subcortical cerebral white matter abnormalities with T2 hyperintensities of the dentate nucleus, globus pallidus, putamen and caudate nucleus. The diagnosis can be confirmed by elevated urinary L-2 hydroxyglutaric acid and mutational analysis of the L-2-HGDH gene. We report two siblings with dystonia diagnosed by classical neuroimaging findings with elevated urinary 2 hydroxyglutaric acid. Riboflavin therapy has shown promising results in a subset of cases, thus highlighting the importance of making the diagnosis in these patients.

An acquired brain injury (ABI) is an injury to the brain, which is not hereditary, congenital, degenerative, or induced by birth trauma. In India, rapid urbanization, economic growth and changes in lifestyle have led to a tremendous increase in the incidence of ABI, so much so that it is being referred to as a 'silent epidemic'. Unlike developed countries, there is no well-established system for collecting and managing information on various diseases in India. Thus it is a daunting task to obtain reliable information about acquired brain injury. In the course of conducting a systematic review on the epidemiology of ABI in India, we recognized several challenges which hampered our effort. Inadequate case definition, lack of centralized reporting mechanisms, lack of population based studies, absence of standardized survey protocols and inadequate mortality statistics are some of the major obstacles. Following a standard case definition, linking multiple hospital-based registries, initiating a state or nationwide population-based registry, conducting population-based studies that are methodologically robust and introducing centralized, standard reporting mechanisms for ABI, are some of the strategies that could help facilitate a thorough investigation into the epidemiology and understanding of ABI. This may help improve policies on prevention and management of acquired brain injury in India.

Studies have suggested that dementia is differentially distributed across populations with a lower prevalence in developing regions than the developed ones. A comparison in the prevalence of dementia across populations may provide an insight into its risk factors. Keeping this in view, a study was planned to evaluate the prevalence of dementia in tribal elderly population. A cross-sectional comprehensive two-phase survey of all residents aged 60 years and older was conducted. Phase one involved screening of all individuals aged 60 and above with the help of a cognitive screen specifically developed for the tribal population. Phase two involved clinical examination of individuals who were suspected of dementia as per the developed cognitive screening test. The results revealed that no individual above 60 years of age in the studied population was diagnosed as a case of dementia. Thereby, pointing out at some unknown factors, which are responsible for prevention of dementia. The differences between the prevalence rate in this study and other studies in India appear to be a function of a valid regional difference. Environmental, phenotypic and genetic factors may contribute to regional and racial variations in dementia. Societies living in isolated hilly and tribal areas seem less predisposed to dementia, particularly age related neurodegenerative and vascular dementia, which are the most common causes for dementia in elderly. This may be because some environmental risk factors are much less prevalent in these settings.

It was estimated that there were 24 million people with dementia in the world in 2005 and this figure is expected to double every 20 years.[1] About 60% of them live in developing countries. This proportion is likely to reach 75% in the next two decades. The disease burden of dementia is expected to rise more in developing countries. The economic burden of care for people with dementia is 1% of the global Gross Domestic Product. Care mechanisms for persons with dementia are rapidly changing in developing countries. Traditionally, elderly and persons with cognitive impairment were looked after at home by their family members, particularly women in the household. In India and several other developing countries, more women are now attaining higher education and getting employed. There is increasing migration of young people to more developed countries. The smaller family concept is leading to fewer persons at home to look after elderly people. As a result of all these influences, the traditional system of domiciliary care for persons with dementia is becoming more difficult. At the same time, suitable and acceptable alternate systems to attend to them are not well established in these countries. This year, the theme for the world Alzheimer’s Day was “Dementia: It is time to act”. This theme draws the attention of the world to the urgent need to focus on the actions required from all quarters – public, administrators, professionals and care givers alike – to ameliorate the burden due to dementia. This supplement focuses attention on the clinical aspects of dementia and its management. I congratulate Dr. Mathuranath for bringing together a host of contributors to write practically important articles for this supplement. He had put in tremendous effort to bring out this supplement. I hope that this supplement will make an excellent learning material for our esteemed readers.

A 13-year-old boy presented with a healing ulcer over the vertex, a healed ulcer above the right eye [Figure 1A], occasional fever, weight loss, diplopia, bilateral proptosis, lagophthalmos and bilateral mild facial palsy. In hospital, he developed left -sided focal seizures and symptoms and signs of raised intracranial pressure. The skull radiograph showed a thickened frontal vault, suggestive of chronic osteomyelitis [Figure 1B]. CT brain conÞ rmed thickening of the skull vault over the right frontal region and revealed an epidural mass in the prefrontal region that was predominantly on the right side but crossed the midline and caused a mass eff ect, with midline shift to the left . Also present was massive white-matt er edema, with eff acement of the ipsilateral ventricle and enlargement of the contralateral one [Figure 1C]. A biopsy from the scalp lesion demonstrated granulation tissue, hematoxyphilic colonies, and gram positive Þ lamentous rods, features that were diagnostic of actinomycosis [Figure 1D]. The boy recovered well withintravenous administration of crystalline penicillin and co-trimoxazole along with oral erythromycin for six weeks, followed by oral co-trimoxazole and erythromycin for six moths. The epidural mass and skull thickening, however, persisted. Clinical features of chronic epidural lesions of the skull and spine can be subtle and treacherous. Signs, rather than the symptoms, of raised intracranial pressure oft en dominate. Spinal lesions may present earlier. Epidural mass lesions can be due to a variety of causes; these include (1) hematoma due to trauma, bleeding diathesis or venous sinus thrombosis; (2) malignant deposits from lymphoma, leukemia, multiple myeloma or chloroma; (3) chronic noninfectious granuloma due to sarcoidosis, eosinophilic granuloma, cholesteatoma, hypertrophic pachymeningitis, Wegener granulomatosis or cranial fascitis; (4) chronic infectious lesions, e.g., aspergillosis or tuberculosis (5); primary neoplasms like chondromas,

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of disorders, characterized by dysfunction of neuromuscular junction (NMJ) transmission. These syndromes are genetically inherited and are present since birth. Some have characteristic clinical or electrodiagnostic features but in many cases determination of the specific form requires genetic studies or specialized morphological and electrophysiological studies on muscle tissue. We report a case of a 4-year-old boy with progressive ptosis and limitation of ocular movements who was diagnosed as slow-channel CMS based on the characteristic electrodiagnostic features. Repetitive compound muscle action potentials (R-CMAPs) were recorded after single nerve stimulus, with decremental response after repetitive trains performed at 3 Hz. CMSs are at times clinically difficult to distinguish from acquired myasthenia. The characteristic clinical and electrodiagnostic features help in the diagnosis and enable rational therapy. In this article we discuss the characteristics of synaptic R-CMAPs.

Thrombolysis with intravenous tissue (IV) plasminogen activator (tPA) is considered for patients with acute ischemic stroke falling within the described inclusion criteria defined by The National Institute of Neurological Disorders and Stroke (NINDS) rtPA trial. Complications of IV thrombolysis with tPA are commonly related to hemorrhage, anaphylaxis, or arterial occlusion. We describe two cases of acute myocardial infarction (MI) following IV tPA infusion for acute stroke. One of the patients had underlying ischemic heart disease (IHD) while the other did not have any prior IHD. Both had presented with acute ischemic stroke within the window period of thrombolysis and had no contraindications for thrombolysis. Both the patients succumbed due to myocardial infarction and cardiovascular collapse due to new onset arrhythmias. Acute MI immediately following IV tPA for stroke is a rare but serious complication. The disruption of intracardiac thrombus and subsequent embolization to coronary arteries may be an important mechanism in the occurrence of MI after administration of tPA for acute ischemic stroke. As both the patients succumbed before the arrangement for coronary angiography, the demonstration of intracardiac or intracoronary thrombus was not possible. But clinically, the presence of chest pain with elevated troponin levels and ST segment elevation pointed to MI. We suspect that fragmentation and lysis of intracardiac thrombus may result in MI after use of tPA for acute ischemic stroke, though the remote possibility of simultaneous occurrence of two atherosclerotic events MI and stroke exists.

Given the constraints of resources, thrombolysis for acute ischemic stroke (AIS) is under evaluation in developing countries like India, especially in areas such as western Utter Pradesh, where it is overly crowded and there is poor affordability. This study was done to evaluate recombinant tissue plasminogen activator r-tpa in acute ischemic stroke in hyper acute phase, in selected patients of western Utter Pradesh, in terms of feasibility and effectivity. Open, non randomized study. Thirty two patients were classified using Trial of ORG 10172 in Acute Stroke treatment (TOAST) criteria (large artery atherosclerotic = 8; cardio embolic = 6; small vessel occlusion = 14; other determined etiology = 2; undetermined etiology = 2). The mean time to reach the hospital was 2 h (1.15-3.0), the mean door to CT scan 20 min (10-40) and door to r-tpa injection was 30 min (24-68). The National Institute of Health Stroke Scale (NIHSS) scores ranged from 11-22 (mean 15.5 +2.7). The dose of r-tpa administered was 0.9 mg/kg. Twenty one patients (65.6%) showed significant improvement on the NIHSS score, at 48 h (4 points). (Mean change = 10; range = 4-17). At one month, 25 (78%) recorded improvement on the Barthel index (mean change = 45%). One developed frontal lobe hemorrhage and another developed recurrent stroke; one died of aspiration; and four showed no improvement. Modified Rankin score (m RS) was administered at the end of three months to 28 patients (90%); however, the rest could not be directly observed. The average modified Rankin Score was 1.2 (0-2). Hyperacute thrombolysis was found feasible and effective in selected patients with AIS from western Utter Pradesh and who had poor affordability.

Migraine is a common neurological disorder with significant impact on quality of life. The aim of this study was to investigate the prevalence and characteristics of migraine headaches in medical students, to measure its impact on their life, and to assess their knowledge about the ailment. Information about lifestyle variables was also collected. All medical students who confirmed of having headache for more than 1 year formed the study group. Students filled a detailed questionnaire focusing on demographics, pain characteristics, accompanying factors, triggers, and family history of migraine. Lifestyle variables were enquired and migraine associated disability was assessed by MIDAS (Migraine Disability Assessment). The diagnosis of migraine was made according to the International Headache Society criteria. Results are expressed in n = numbers and percentage. Sixty-eight percent of medical students had headache. The prevalence of migraine in the whole cohort was 28%; however, of the headache group, migraine constituted 42%. There was a female preponderance. One-fourth of the students had weekly or daily attacks with 31% students reporting increase in their headache intensity and frequency. Forty-four percent of students had severe headaches. Dizziness, allodynia, and neck stiffness were reported as accompanying symptoms. Trigger factors were identified in 99% students, predominant of which were poor sleep hygiene, environmental changes, head movements, and mental stress. Only 4% of students did regular exercise. Twenty-seven percent of students reported self-medication use of analgesics. One-fourth of the students had migraine-associated disability but only 6% realized that they had migraine. Our study found a high prevalence of headache with migraine in medical students. The students' awareness of the disease was very low with one-fourth of the students resorting to self-medication. Our study identified previously less-recognized triggers like head movement and accompanying symptoms like neck stiffness. Migraine-attributed burden was high in medical students.

A number of studies have shown the impact of cognitive abilities on instrumental activities of daily living, in particular executive functions. Nevertheless, it is not clear to what extent these results can be generalized, given that most samples studied have not included people with a low educational level. The current study aims to investigate the association between cognitive abilities and activities of daily living in older adults - with and without dementia - from a middle-income country. The sample consisted of 48 healthy older adults and 29 people with dementia, who were evaluated in an Outpatient Care Unit in a University Reference Center in Rio de Janeiro. Regression analyses indicated that the best predictors for activities of daily living were performance in immediate verbal memory in the case of controls and in a categorical fluency task in the patient group. The educational level itself was not a significant predictor of functional ability in either sample, but showed moderate correlation with the predictors. These results suggest that educational level may be a mediating factor in the association of cognitive variables and activities of daily living, and indicate a potential dissociation in terms of predictors according to the diagnostic status, pointing to relevant treatment directions.