Spectrum of Neurological Illnesses in Pregnancy - An Observational Study from a Tertiary Care Centre of Eastern India.

INTRODUCTION: Neurological disorders in pregnancy may be observed in patients with a pre-existing neurological disorder; patients developing a primary neurological disorder during the course of pregnancy or puerperium; and in patients with primary medical disorders presenting with neurological manifestations. OBJECTIVES: The objectives of the study were to find out the magnitude of neurological disorders in pregnancy in a tertiary care hospital along with assessment of proportion of women with particular disorders among total number of neurological disorders during the course of pregnancy or puerperium (6 weeks after child birth) and also to elicit the effect of neurological disorders on pregnancy outcome, if any. METHODS: A prospective observational longitudinal study was carried out in a tertiary care centre of Eastern India from July 2018 to June 2020 including all pregnant women attending the department of Obstetrics and Gynaecology. We screened 886 pregnant women, out of which 91 cases were identified and investigated. For the purpose of comparison of fetal and maternal outcome, 91 control subjects were chosen from the screened patients in a randomized fashion, so that the baseline characteristics of the two groups were comparable Results: In our study, 10.3% population had neurological disorders, among which 30.8% had primary headache, 3.2% had secondary headache, 8.5% had neurological low back pain, 19.1% had epilepsy, 6.4% had cerebrovascular disorders, 27.6% had peripheral neuropathy, 4.2% had other disorders such as neuropsychiatric Wilson's disease, myasthenia gravis and compressive myelopathy. Moreover, 10.2% of the total study population was hypertensive and 2.9% were diabetic. CONCLUSION: 10.3% mothers did have some neurological disorder, the commonest of which was migraine (primary headache) followed by carpal tunnel syndrome (peripheral neuropathy) and neurological low back pain. Overall fetomaternal outcomes were favorable barring cerebro-vascular disorder and Posterior reversible encephalopathy syndrome (PRES). We recommend screening for neurological disorder from early pregnancy for early detection and appropriate management of that condition.

Comparative Study of Risk Factors and Cognitive Profile of Small- and Large-Vessel Vascular Dementia - A Clinic Based Study.

Background: Vascular dementia (VaD) is a clinically heterogeneous entity. There is a dearth of studies for comparison of the cognitive profile of cerebral small-vessel disease (SVD) with large-vessel disease. Objective: We planned to evaluate and compare the cognitive profile of SVD and large-vessel VaD and evaluate various risk factors associated with them. Materials and Methods: Patients of VaD were recruited after excluding mixed and ambiguous cases. Patients were classified into SVD and large-vessel VaD and analyzed for their clinic-epidemiological and cognitive profiles. Results: Among 76 patients, 48 (62.5%) have SVD and 28 (37.5%) have large-vessel disease. Hypertension (93.4%) was the commonest risk factor, followed by smoking (34.21%), hyperlipidemia (26.31%), and diabetes mellitus (DM, 22.36%). Hypertension (P < 0.05) and DM were common in SVD, whereas smoking, hyperlipidaemia, and cardiac diseases were common in large-vessel disease. Attention (77.1% vs 25%), executive function (68.8% vs 28.6%), and calculation (58.3% vs 32.1%) were significantly more impaired in SVD compared to large-vessel disease, whereas visuoperceptual (21.4% vs 6.3%), praxis (28.6% vs 4.2%), and gnosis (14.3% vs 2.1%) were significantly more impaired in large-vessel disease than in SVD. Disruption of frontal-subcortical connection was responsible for the cognitive profile in SVD, but in large-vessel disease, it resulted from the cumulative loss of function from different lesions. Conclusions: Despite having common vascular risk factors, few are more common in SVD than in large-vessel disease. The different clinical and cognitive profile is due to the diverse anatomical lesions in these two subclasses of VaD.

Correlation of ATP7B gene mutations with clinical phenotype and radiological features in Indian Wilson disease patients.

INTRODUCTION: Wilson disease (WD) is characterized by a wide variety of clinical manifestations. Our study aimed to correlate genotype with clinical and radiological features in Indian WD patients. METHODS: We conducted a descriptive observational study in a tertiary care neurology referral center of eastern India over a period of 2 years. Demographic data collection, clinical examination and relevant investigations were done for all WD patients meeting the inclusion criteria. Based on previous reports of mutation hotspots for WD in Eastern India, we performed PCR-Sanger sequencing of selected exons of ATP7B gene. To understand the role of each of these covariates on the occurrence of common mutation, we applied a logistic regression as well as random forest in a supervised learning framework. RESULTS: Fifty-two WD patients were included in the study. c.813C > A (p.C271X) was the commonest identified mutation. The statistical methods applied to our data-set reveal the most important features for predicting common mutation or its absence. We also found that the state-of-the-art classification algorithms are good at predicting the absence of common mutation (with true positive rates being 0.7647 and 0.8823 for logistic classifier and random forest, respectively), but predicting the occurrence remains a harder modeling challenge. CONCLUSIONS: WD patients in eastern India have significant genotypic and phenotypic diversity. Statistical methods for binary classification show some early promise of detecting common mutations and suggest important covariates, but further studies with larger samples and screening of remaining exons are warranted for understanding the full genetic landscape of Wilson disease.

Not the Stereotypical Wilson Disease: A Case Report.

Background: Wilson disease (WD), a potentially treatable genetic disorder with perturbations in copper metabolism, presents with hepatic and neuropsychiatric manifestations. Both hyper and hypokinetic movements predominate the latter spectrum. Motor stereotypies, however, are exceedingly rare. Case Report: We present a case of a 12-year-old girl, with progressive behavioural alterations and cognitive impairment, with motor stereotypies involving the upper limbs, as the dominant movement semiology. She was diagnosed as WD with evidence of striatal involvement on brain imaging. Her motor symptoms partially responded to chelation therapy. Discussion: There are about five documented cases of motor stereotypies in WD worldwide, with only one being previously reported from India.

Predicting Long-Term Outcome of Patients of Early Parkinsonism with Acute Levodopa Challenge Test.

OBJECTIVES: The aim of this study was to evaluate the sensitivity and specificity of various outcomes of acute levodopa challenge test (ALCT) namely improvement of motor function, development of dyskinesia and intolerance; to predict the diagnosis of idiopathic Parkinson's disease (IPD) or Parkinson-plus syndrome; to predict levodopa responsiveness and levodopa-induced dyskinesia (LID) during long-term therapy. METHODS: ALCT was performed on 89 patients with parkinsonism of <2 years and were followed up for 18 months. Improvement of UPDRSm by ≥30% was considered positive. RESULTS: The test was positive in 37 (43.5%) and negative in 48 (56.5%) of 85 patients completing it. Of the 75 patients completing 18 months' follow-up 34 (45.3%) were diagnosed as IPD. A positive ALCT predicted a clinical diagnosis of IPD with sensitivity and specificity of 97.4% and 70.7% respectively. The predictive value of ALCT for long-term levodopa responsiveness was less than predicting a diagnosis of IPD. While appearance of dyskinesia during ALCT had a low predictive value for future LID (sensitivity 14.3%), it had high predictive value for a diagnosis of multisystem atrophy (MSA) (91% specificity and 37.5% sensitivity). The appearance of symptoms of levodopa intolerance (SLI) during ALCT could predict a clinical diagnosis of MSA with high specificity (95.5%) and moderate sensitivity (50%). CONCLUSION: Levodopa responsiveness during ALCT was useful in predicting a diagnosis of IPD but not long-term response to levodopa. The development of dyskinesia during ALCT could not correctly predict LID, but could predict a diagnosis of MSA. The appearance of SLI during ALCT could also predict MSA correctly.

Behavioural and Psychological Symptoms of Dementia: Correlates and Impact on Caregiver Distress.

AIMS: To evaluate the behavioural and psychological symptoms of dementia (BPSD), to determine their correlation with types and stages of dementia and patient demographics, and to assess the impact on caregiver distress. METHODS: This cross-sectional study recruited consecutive dementia patients and caregivers who attended our cognitive clinic. Standard criteria were used to classify types of dementia. BPSD were assessed with the Neuropsychiatric Inventory, and its distress scale was used for caregiver distress. RESULTS: Of a total 107 patients, nearly all (99.1%) had at least one BPSD; 71% had ≥4 symptoms. Most frequent were apathy and agitation, followed by irritability, sleep and appetite disorders, and mood disorders; disinhibition and euphoria were least frequent. BPSD were less prominent with increasing age; males showed more agitation. Apathy and eating disorders were more prevalent in the rural community. BPSD were highest in frontotemporal dementia (FTD), followed by dementia with Lewy bodies (DLB), and least in vascular dementia. Hallucinations were more common in DLB, aberrant motor behaviour in FTD. All domains of BPSD, except for anxiety and euphoria, were more prominent with increasing severity of dementia. Increasing BPSD (except for euphoria) caused higher caregiver distress. CONCLUSION: BPSD are universally present, bear correlates with dementia type and severity, and cause significant caregiver distress.

Study of visuospatial skill in patients with dementia.

OBJECTIVES: To assess the visuospatial function in different types of dementia with the visual object and space perception (VOSP) battery and to relate the degree of visuospatial dysfunction with different types and stages of dementia. MATERIALS AND METHODS: A sample of 53 participants with dementia and equal number of age-, sex-, and education-matched controls were recruited for the study. Participants were evaluated for visuospatial skill using VOSP test battery. The scores of dementia patients were compared with controls and within dementia cohort scores were compared based on stage of dementia. RESULTS: The dementia group scored low in all of the subtests of the VOSP battery in comparison to controls. Alzheimer's disease (AD), dementia of Lewy bodies (DLB), and vascular dementia (VaD) patients performed more poorly than controls in all subtests examining object perception and space perception. The three semantic variants of frontotemporal dementia (FTD) patients scored low in all four subtests of object perception, whereas behavioral variant FTD (bvFTD) patients performed normally. The scores deteriorated with the advancement of dementia in all patients from the dementia groups. CONCLUSIONS: Visuospatial function is significantly impaired in dementia patients particularly in AD, DLB, and VaD patients from the beginning, and the impairment is severe in advanced disease stages.

Genetic and Clinical Profile of Patients of Duchenne Muscular Dystrophy: Experience from a Tertiary Care Center in Eastern India.

OBJECTIVE: To study the genetic pattern, clinical profile and to find any correlation between them in patients of Duchenne muscular dystrophy. METHODS: Patients were selected from Neurogenetic clinic on the basis of clinical features, elevated serum CPK level and electromyographic features. After history and clinical examination, molecular genetic testing was performed by Polymerase Chain Reaction (PCR) technique. RESULTS: Among 100 patients, 73 patients had genetically confirmed disease while 8 cases were proven by biopsy, and thus a total 81 cases were further taken up for the study. Mean age of onset of clinical symptoms was 3.9 yrs; Valley sign and calf hypertrophy were most consistent features, while about 51% had facial weakness. Out of 73 genetically confirmed cases 53 (72.6%) showed deletion in distal exons and 12 (16.4%) showed deletion in both proximal and distal exons while 8 (10.9%) had only proximal deletion. There was no correlation between genetic pattern and clinical features. CONCLUSIONS: The positivity of PCR- based diagnosis is higher in our study possibly related to highly selective group of patients. Phenotype and genotype correlation was not seen.

Retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease.

Paranasal sinus disease can cause a condition that mimics optic neuritis. Simultaneous appearance of both diseases would create etiological dilemma. We report two cases of retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease. In the case of a 65-year-old female who had presented with acute loss of vision in the left eye associated with left-sided frontal headache which subsequently turned out to be caused by optic nerve compression at the orbital apex due to collection in abnormally pneumatized left lesser wing of the sphenoid. In another case, a 65-year-old lady had presented with symptoms of bilateral retrobulbar optic neuropathy which was found to be due to direct compression of optic nerves at the orbital apex secondary to metastases from breast carcinoma.

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia.

BACKGROUND/AIMS: The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD). MATERIALS AND METHODS: We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l'Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively. RESULTS: We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD. CONCLUSIONS: BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.

Clinical features, MRI brain, and MRS abnormalities of drug-naïve neurologic Wilson's disease.

BACKGROUND: Magnetic resonance imaging (MRI) helps in the diagnosis of neurologic Wilson's disease (WD). The literature regarding MR spectroscopy (MRS) and diffusion-weighted imaging (DWI) in WD is limited. OBJECTIVES: To evaluate the clinical features and neuroimaging findings in drug-naïve neurologic WD and to find correlation between clinical stage and disease duration with different imaging findings. MATERIALS AND METHODS: The study subjects included consecutive and follow-up neurologic WD patients attending movement disorder clinic. The initial clinical and MRI features before commencement of chelation therapy were noted. Of 78 patients, 34 underwent DWI study and MRS was done in 38 patients and in 32 control subjects. RESULTS: Dystonia, dysarthria, tremor, and behavioral abnormality were common presenting features. All patients had MRI abnormality with major affection of basal ganglia. The clinical severity and anatomical extent of MRI abnormalities were positively correlated (P < 0.001; r s = 0.709). Presence of diffusion restriction was inversely related to duration of disease (P < 0.001; r s = 0.760). WD patients had reduced N-acetylaspartate/creatine (Cr) and choline (Cho)/Cr ratio (P < 0.001) as compared with control subjects in MRS study. CONCLUSION: Dystonia, dysarthria and tremor are common neurological features of WD. In this study, MRI abnormalities were positively correlated with disease severity; diffusion restriction was inversely correlated with the duration of the disease process. MRS was also a sensitive tool for diagnosing patient of neurologic WD.

Case series of probable sporadic Creutzfeldt-Jakob disease from Eastern India.

BACKGROUND: Creutzfeldt-Jakob disease is a rapidly progressive, fatal, transmissible neurodegenerative disorder caused by prion protein. It is still considered rare in countries like India. This is probably due to nonavailability of autopsy studies in majority of the center. The recent European diagnostic criterion for sporadic CJD (sCJD) is useful for making an early diagnosis. OBJECTIVE: To report a series of patients of probable sCJD from a neurology institute of eastern India. MATERIALS AND METHODS: Patients of rapidly developing dementia fulfilling the diagnostic criteria for sCJD were included. All were investigated in detail to find out any possible treatable cause including electroencephalography (EEG), magnetic resonance imaging (MRI) of brain, and cerebrospinal fluid analysis. RESULTS: A total 10 patients of probable sCJD diagnosed using the European diagnostic criterion between December 2011 and January 2013. The clinical features are consistent with other reported series. While 60% of patients had the classical EEG findings, 100% had typical MRI features. Eight patients died within a mean duration of 4.56 months from the disease onset. CONCLUSIONS: The clinical features are similar to other reported series. Our observation raises question about the prevalence of this disease in India which needs more elaborate studies.