Prevalence of Cognitive Impairment and Dementia After Intracerebral Hemorrhage.

Objective: To study the prevalence of cognitive impairment in survivors of intracerebral hemorrhage (ICH). Methods: Survivors of spontaneous ICH were followed up in the neurology outpatient department when they reported for follow-up after 6 months. Neuroimaging records at the onset and at follow-up visits are studied for the location of ICH, volume of ICH, intraventricular extension, and hydrocephalus. The volume of ICH is calculated by ABC/2 method on a CT scan. All patients underwent cognitive assessment with Addenbrooke's cognitive examination ACE III and were categorized as patients having cognitive impairment (or) no cognitive impairment. Results: A total of 120 patients were studied, out of which 77 (64%) are males and 43 (36%) are females with age groups ranging from 26 to 75 years. In the study population, the mean age was found to be 62.3 years. Specifically, the mean age for males was 56.9 years, while for females it was 63.4 years. Cognitive impairment was noted in 34 of 120 patients (28%) during 6 to 12 months of examination, of which 11 of 19 were in lobar location, 21 of 94 were in sub-cortical location, and 2 of 7 were in infratentorial location. Conclusion: It was found that 28% of survivors of ICH were cognitively impaired. Hence, it is essential to assess cognition in post-ICH patients during follow-up, so that suitable adjustments can be made in their employment, and also in educating family members in providing a good quality of life.

Frontotemporal Dementia - Current Concepts.

Frontotemporal dementia (FTD) is an entity that includes a group of neurodegenerative disease with symptoms predominantly pertaining to deficits in behavior, executive function (or) language. FTD is one of the most common type of dementia before 65 years of age and is one of the most underdiagnosed dementia as most often the symptoms overlap with psychiatric manifestations. Based on the clinical features, FTD is further subdivided into behavioral variant FTD (Bv-FTD) and primary progressive dementia (PPA). We searched PubMed, MEDLINE, and Google Scholar for articles about FTD disease published in English between January 1, 1975 till 2018. We used the search terms "frontotemporal dementia," "Fronto temporal dementia-motor neuron disease," "dementia," "cognition," "behavioral variant," and "primary progressive aphasia.

Neurological Melioidosis Presenting as Rhombencephalitis, Optic Neuritis, and Scalp Abscess with Meningitis: A Case Series from Southern India.

Melioidosis is an under recognized infectious disease which may rarely present with neurological involvement. Neurological melioidosis has protean manifestations, and in this case series we present 3 patients diagnosed from a single center in southern India. The clinical presentation of the patients we describe includes rhomb-encephalitis, scalp infection with subdural and meningeal involvement, and optic neuritis associated with pulmonary melioidosis. We discuss the possible mechanism of involvement of the nervous system, and the recommended treatment. Diagnosis of melioidosis requires a high index of suspicion and should be considered in endemic areas. Through this series we hope to improve the awareness of this infection and its neurological presentation.

Lipid transfer proteins and instructive regulation of lipid kinase activities: Implications for inositol lipid signaling and disease.

Cellular membranes are critical platforms for intracellular signaling that involve complex interfaces between lipids and proteins, and a web of interactions between a multitude of lipid metabolic pathways. Membrane lipids impart structural and functional information in this regulatory circuit that encompass biophysical parameters such as membrane thickness and fluidity, as well as chaperoning the interactions of protein binding partners. Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play key roles in intracellular membrane signaling, and these involvements are translated into an impressively diverse set of biological outcomes. The phosphatidylinositol transfer proteins (PITPs) are key regulators of phosphoinositide signaling. Found in a diverse array of organisms from plants, yeast and apicomplexan parasites to mammals, PITPs were initially proposed to be simple transporters of lipids between intracellular membranes. It now appears increasingly unlikely that the soluble versions of these proteins perform such functions within the cell. Rather, these serve to facilitate the activity of intrinsically biologically insufficient inositol lipid kinases and, in so doing, promote diversification of the biological outcomes of phosphoinositide signaling. The central engine for execution of such functions is the lipid exchange cycle that is a fundamental property of PITPs. How PITPs execute lipid exchange remains very poorly understood. Molecular dynamics simulation approaches are now providing the first atomistic insights into how PITPs, and potentially other lipid-exchange/transfer proteins, operate.

Socioeconomic consequences of drug-resistant epilepsy in an adult cohort from southern India.

OBJECTIVE: The objective of this study was to describe the socioeconomic consequences of drug-resistant epilepsy (DRE). METHODS: This study comprised 132 (equal males and females) consecutive patients aged ≥18 years, who fulfilled the International League Against Epilepsy (ILAE) definition for DRE, prospectively seen in a tertiary care center in South India. We used a structured questionnaire to gather relevant information. RESULTS: The mean age was 31 (range 18-70) years. Mean age of onset of epilepsy was 17 years and mean duration of epilepsy 14 years. The most common epilepsy type and etiology were focal epilepsy and gliotic lesions secondary to perinatal insults, respectively. The average out of the pocket expenditure on antiseizure drugs annually amounted to 19% of the gross national product (GNP)/capita, which was borne by family members in more than two-thirds of the subjects. Almost 60% reported epilepsy having affected their education, 40% their employment, and 90% their marital prospects. Female patients were less often employed outside their homes and had more marital problems compared with males. CONCLUSIONS: In addition to high seizure burden, DRE adversely affects the pursuit of higher education, employment, and marriage. Besides the direct cost of epilepsy, these issues augment both the patient and the caregiver's liability. Socioeconomic consequences of DRE are widely prevalent in developing countries, and this study highlights the need to address them.

Sex-chromosome dosage effects on gene expression in humans.

A fundamental question in the biology of sex differences has eluded direct study in humans: How does sex-chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex-chromosome aneuploidies (XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity among evolutionarily preserved X-Y homologs and update prevailing theoretical models for SCD compensation by detecting X-linked genes that increase expression with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex-chromosome genes regulate specific coexpression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. These gene coexpression results converge with analysis of transcription factor binding site enrichment and measures of gene expression in murine knockout models to spotlight the dosage-sensitive X-linked transcription factor ZFX as a key mediator of SCD effects on wider genome expression. Our findings characterize the effects of SCD broadly across the genome, with potential implications for human phenotypic variation.

Clinical mimics of acute appendicitis: Is there any role of imaging?

Acute appendicitis (AA) is a common surgical emergency. Accurate and timely diagnosis of AA is essential for successful outcome. Imaging plays an important role in the diagnosis, exclusion of AA as well as diagnosing alternative clinical conditions which can closely simulate AA. A correct alterative diagnosis may obviate the need of unnecessary appendectomy or may even change the treatment regime altogether. This pictorial essay illustrates various clinical conditions which mimicked AA clinically during our day to day practice.

Are patients with limb and head tremor a clinically distinct subtype of essential tremor?

BACKGROUND: Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT-) are few. METHODS: To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. RESULTS: HT was present in 44.4% of the patients. Comparison between HT+ and HT- showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. CONCLUSIONS: Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.

Multimodal evoked potentials in spinocerebellar ataxia types 1, 2, and 3.

AIMS: Spinocerebellar ataxias (SCA) are a clinically heterogeneous group of disorders that are characterized by ataxia and an autosomal dominant pattern of inheritance. The aim of our study was to describe the findings of evoked potentials (EPs) among genetically proven SCA types 1, 2, and 3 and to additionally evaluate if EPs can be used to differentiate between them. MATERIALS AND METHODS: Forty-three cases of genetically proven SCA (SCA1 = 19, SCA2 = 13, and SCA3 = 11) were evaluated with median somatosensory-EP (mSSEP), visual-EP (VEP), and brainstem auditory-evoked response (BAER) by standard procedures and compared with normative laboratory data. An EP was considered abnormal if latency was prolonged (>mean + 3 standard deviation (SD) of laboratory control data) or the waveform was absent or poorly defined. The waves studied were as follows: mSSEP - N20, VEP - P100 and BAER - interpeak latency 1-3 and 3-5. RESULTS: EPs were abnormal in at least one modality in 90.9% of patients. The most common abnormality was of BAER (86.1%) followed by VEP (34.9%) and mSSEP (30.2%). The degree of abnormality in VEP, mSSEP, and BAER among patients with SCA1 was 42.1, 41.2, and 73.3%, respectively; among patients with SCA2 was 38.5, 27.3, and 100%, respectively; and among patients with SCA3 was 18.2, 37.5, and 88.9%, respectively. The differences between the subgroups of SCAs were not statistically significant. CONCLUSIONS: BAER was the most frequent abnormality in SCA types 1, 2, and 3; abnormalities of mSSEP were comparable in the three SCAs; whereas, abnormality of VEP was less often noted in SCA3.

Niemann-Pick disease type C or Gaucher's disease type 3? A clinical conundrum.

We describe a patient who presented with a neurovisceral syndrome characterised by ataxia, bulbar dysfunction, supranuclear gaze palsy, splenomegaly and foamy histiocytes in the bone marrow. This presentation was suggestive of a lysosomal storage disorder such as Niemann-Pick disease type C or Gaucher's disease type 3. We review the presentation of these disorders, with a focus on the neurological features. In addition, we briefly discuss the disease-modifying therapeutic options which have recently become available.

Bilateral medial medullary syndrome secondary to Takayasu arteritis.

Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA.

Calcified embolism: a rare cause of cerebral infarction.

Calcified cerebral emboli (CCE) are a rare cause of stroke and these emboli can be identified on a CT scan of the brain performed for the initial evaluation of stroke. In this report we present a patient who developed a CCE following cardiac catheterisation that lodged in the left middle cerebral artery with resultant right hemiparesis and aphasia. The calcified embolus was seen on CT but could not be identified on MRI. Predisposing factors for CCE include angiography and valve or vessel wall calcification. The natural history and response to standard therapy in patients with CCE as compared with stroke of other aetiologies have not been studied until now. Increased awareness and ability to identify calcified emboli will help us to have an improved understanding of strokes resulting from CCE.

Quality of life and its determinants in essential tremor.

INTRODUCTION: Despite Essential Tremor (ET) being the commonest movement disorder, there are few studies on the quality of life (QOL) in patients with ET, with most studies employing generic questionnaires. METHODS: We studied QOL in 50 patients with ET attending the outpatient of a hospital using the Quality of life in Essential Tremor (QUEST) questionnaire a disease specific QOL instrument. The severity of tremor was assessed using a modified Fahn Tolosa Marin tremor rating scale (mFTMRS), co morbid anxiety and depression were studied using the Hamilton Anxiety (HARS) and Depression (HDRS) rating scales respectively. We also analyzed the influence of gender, age at presentation, age of onset, duration of tremor, distribution of tremor, family history and use of medications on the QOL. RESULTS: The mean age of onset of tremor was 32.2 ± 18.9 years, mean duration of tremor was 8.4 ± 10.0 years, mean QUEST summary index (QSI) was 24.2 ± 19.2; mean scores in each of the domains were as follows--physical 29.3 ± 26.7, psychosocial 36.4 ± 28.7, communication 23.9 ± 36.9, work & finance 23.5 ± 29.9, hobbies 6.8 ± 17.3. The QSI had significant positive correlation with the mFTMRS, HARS and HDRS. Gender, age at presentation, age of onset, duration of tremor, distribution of tremor, family history and use of medication did not influence the QOL. CONCLUSION: Psychosocial aspects are important in determining the QOL in patients with ET. Tremor severity, co morbid anxiety and depression are associated with a lower QOL whereas tremor characteristics like age of onset, duration, distribution do not influence the QOL.

Diffusion tensor imaging: tract based spatial statistics study in essential tremor.

INTRODUCTION: Essential tremor (ET) is a common movement disorder with motor and non-motor symptoms. We aimed to investigate the neurodegenerative changes in the brain white matter of patients with ET using Diffusion Tensor Imaging (DTI). METHODS: Clinical and MRI data from 20 patients (5 women and 15 men; age-38.2 ± 16.5 yrs) with ET and 17 controls (3 women and 14 men; age-40.7 ± 16.5 yrs) were collected prospectively. The DTI data were analyzed using tract based spatial statistics (TBSS) software for tract wise analysis. Further region of interest (ROI) analysis was carried out in the genu of corpus callosum, anterior limb of internal capsule (ALIC), corticospinal tract (CS), and cerebellar peduncles. Effect of tremor severity, disease duration and age of onset on DTI metrics was also studied. RESULTS: Patients with ET in comparison to controls showed significant (P(corrected) < 0.05) increase of mean diffusivity and radial diffusivity in right frontoparietal white matter. Axial diffusivity increase was seen in bilateral cerebral hemispheres, thalamus, brainstem and cerebellar hemisphere white matter. No significant change in fractional anisotropy of the white matter was seen. ROI analysis also revealed abnormalities in the ALIC and cerebellar peduncles. There was no correlation between the severity of white matter changes and clinical tremor severity score as well as disease duration. CONCLUSIONS: This study provides in vivo evidence for axonal disintegration of the cerebral and cerebellar white matter fibres in patients with ET.

Essential tremor: beyond the motor features.

There is a growing evidence to suggest that apart from motor features, patients with Essential Tremor (ET) may have significant non-motor features. This review critically analyzes the available evidence of the various non-motor symptoms in patients with ET. Apart from tremor, patients with ET have been reported to have: (i) cognitive abnormalities characterized by mild frontal dysfunction that may have a functional impact, (ii) an association with dementia (both prevalent and incident) among those with late onset of tremor (>65 years), (iii) a higher prevalence of anxiety and an anxious and worrisome personality type, (iv) depressive symptomatology and may even have depression as a premotor symptom, (v) poor sleep quality and (vi) subjective hearing impairment. It is controversial whether olfactory dysfunction occurs in ET and its utility as a diagnostic aid. The biological basis for each of these observations requires further clarification and some findings need confirmation in population-based studies. However the available evidence is sufficient to support the notion that ET can no longer be considered as a pure motor disorder and further studies of these non-motor aspects will go a long way in understanding and comprehensively treating ET.

Decrease in cerebral and cerebellar gray matter in essential tremor: a voxel-based morphometric analysis under 3T MRI.

BACKGROUND AND PURPOSE: Though routine neuroimaging is usually normal in essential tremor (ET) there is clinical evidence of widespread involvement of central nervous system. This study aimed at determining morphological changes in brain of patients with ET using voxel-based morphometry (VBM) analysis and also compare the subtypes of ET. METHODS: Clinical and imaging data of 20 patients (5 women, 15 men; mean age 38.2 ± 16.5 years) of ET were collected prospectively. To determine areas of gray matter (GM) atrophy, T1W volumetric MRI data of patients were compared with 17 matched control subjects using VBM analysis with Statistical Parametric Mapping 5. RESULTS: Compared to controls, patients showed scattered areas of cerebral and cerebellar atrophy. Voxel-wise analysis of patients with and without head tremor showed widespread areas of GM atrophy in cerebral hemispheres of patients with head tremor. No difference was observed between the familial and nonfamilial subgroups of ET. Multiple regression analysis revealed relationship between GM atrophy and tremor severity score. CONCLUSIONS: Patients with ET showed widespread areas of atrophy in both cerebellum and cerebral GM, which supports the current concept of the progressive and diffuse nature of ET. Patients with additional head tremor may represent a distinct subgroup of ET.