Unmasking bipolarity in recurrent depressive disorder following herpes simplex virus triggered n-methyl-D-aspartate encephalitis.

OBJECTIVE: Herpes simplex virus (HSV) infection triggered n-methyl-D-aspartate (NMDA) encephalitis can lead to varied neuropsychiatric manifestations, including movement disorders and manic symptoms. HSV is known to affect the same brain regions as in secondary mania. METHOD: We present a 35-year-old female diagnosed with recurrent depressive disorder (RDD) who developed NMDA encephalitis triggered by HSV infection. RESULT: HSV-triggered NMDA encephalitis led to a manic switch in a woman with RDD on antidepressants, along with the new onset of dyskinetic movements. CONCLUSION: A neurological insult predisposed our patient to the variable effects of antidepressant drugs.

Trends of CNS Cryptococcosis during Pre- and Post-HIV era: A 38 years' retrospective cohort analysis from south India.

OBJECTIVE: Central nervous system cryptococcosis (CNSc) is an AIDS defining opportunistic infection. This retrospective study aimed to analyze the changing epidemiology of CNSc cases from the period of pre- to post-emergence of HIV epidemic in south India. METHODS: Confirmed cases of CNSc from 1978 to 2015 were analyzed for demographic and clinical details with special reference to the cases diagnosed in south India during the period 1952-1977. Geographical distribution, affected age groups, clinical aspects, and comorbidities in relation to immune status were analysed RESULTS: The highest number of CNSc cases (n = 125) were recorded in 2006, with 89.6% HIV positivity. The highest HIV-positivity (93.6%) was documented in the years 2002 and 2009. CNSc cases have majorly changed after the introduction and spread of HIV in terms of predisposing factors, comorbidities, severity, affected age groups and treatment. Notably, an overall rise was observed in non-HIV associated CNSc cases from 1997 (8.1%) to 2015 (16.9%). CONCLUSION: The peak of CNSc had already reached in south India during 2005-2006. However, the number of new infections has slowly decreased in last ten years. Progressive awareness and, early diagnosis of HIV and cryptococcosis, adequate availability of HAART and potential antifungal therapy has played crucial roles in changing epidemiology of the CNSc and its associated mortality.

Cribriform Appearance of White Matter in Canavan Disease Associated with Novel Mutations of ASPA Gene.

Cribriform appearance of the brain in Canavan disease is a rare finding. The two presented cases broaden the magnetic resonance imaging (MRI) phenotype wherein numerous oval, cystic structures, a few resembling dilated Virchow-Robin (VR) spaces, were noted in the centrum semiovale, periventricular, and lobar white matter producing a cribriform pattern. Besides, discrete round to oval cysts were present at the gray-white matter junctions in the second case, which were larger and appeared morphologically distinct from the VR spaces. These cysts did not elongate in any plane on imaging and were more representative of giant intramyelinic vacuoles. Genetic analysis revealed novel mutations in the aspartoacylase or ASPA gene that possibly accounts for the severe form of Canavan disease, which probably explains the imaging findings. The multicystic appearance of the white matter in Canavan disease is unusual and possibly represents two different histopathological substrates.

Comparison of 3D Double Inversion Recovery (DIR) versus 3D Fluid Attenuated Inversion Recovery (FLAIR) in precise diagnosis of acute optic neuritis.

BACKGROUND: The small size, intraorbital fat, perioptic CSF sheath and air-bone interface pose challenges to optic nerve imaging in cases of acute optic neuritis. The study is intended to compare the diagnostic accuracy of 3-dimensional Fluid Attenuation Inversion Recovery (3D FLAIR) and 3-dimensional Double Inversion Recovery (3D DIR) in cases of acute optic neuritis (AON). METHODS: Cases of AON with visual evoked potentials (VEP) abnormality were recruited and compared with controls. Imaging protocol incorporated 3D FLAIR and 3D DIR to routine sequences. The optic nerve signal was evaluated for hyperintensity across three segments viz, intraorbital, prechiasmatic, and optic-chiasm segments. The inter-modality agreement, odds ratio, receiver operator characteristics (ROC) curve, Signal intensity ratio (SIR) and interobserver agreement (between two experienced neuroradiologists) was compared between the sequences. RESULTS: Good Intermodality agreement (IMA) was found in the PC segment (ICC: 0.748, p < 0.001) in the Likert scale. In a binary scale of analysis (signal Normal vs abnormal) Kappa was highest for the PC segment (0.525, p < 0.001). The 3D-DIR sequence had an overall higher odds ratio (OR) of detecting abnormality compared to 3D-FLAIR. OR was highest for 3D DIR in the Orbital segment (OR: 3.64, P-value < 0.001) and for FLAIR in the chiasmal segment (OR 2.25, P = 0.007) for predicting optic neuritis. The area under the ROC curve for 3-D DIR was larger across all the segments (0.8 vs 0.623, p < 0.001). The Area under ROC for signal intensity ratio was higher for 3D-DIR(0.844 vs 0.704, p = 0.004) CONCLUSION: 3D DIR, under its unique contrast-generating scheme, demonstrates a greater diagnostic accuracy and offers confidence in the diagnosis of AON lesions when compared to 3D FLAIR.

GeneXpert: A Rapid and Supplementary Diagnostic Tool for Tuberculous Meningitis, Experience from Tertiary Neurocenter.

Background Tuberculous meningitis (TBM) is a highly lethal form of central nervous system tuberculosis (CNS TB) that causes high mortality and morbidity in children and adults. Nonspecific clinical presentation and fewer TB bacilli challenge clinicians resulting in delays in diagnosis and treatment. Aim This study aimed to evaluate the utility of GeneXpert alone and in combination with culture using 1 mL of cerebrospinal fluid (CSF) in a volume constraint situation. Methods A total of 125 clinically confirmed TBM and 110 non-TBM cases, comprised of both infectious and noninfectious diseases. were included in the study. Patient details including clinical signs and symptoms, CSF, and imaging data were collected from the case records. CSF samples were obtained from all the patients and were tested by the mycobacterial culture method and GeneXpert test. The performance of both the tests was statistically calculated and reported in the form of sensitivity and specificity. Results Out of 125 TBM cases, 40 were detected positive by culture and 26 by GeneXpert. All 110 non-TBM cases were identified negative by both methods. The sensitivity and specificity of GeneXpert in comparison with culture were 27 and 100%, respectively. The culture was found to be more sensitive (32%) than GeneXpert. But the assay was able to detect a considerable number of clinically confirmed culture-negative TBM cases. Conclusion GeneXpert is a rapid test and including this as an adjunctive test along with the culture in routine clinical practice can improve the diagnosis of TBM in volume constraint scenario.

Neurobrucellosis: A neglected entity? An update from tertiary care Neurocentre of South East Asia.

Neurobrucellosis is the most serious complication of brucellosis with neither a typical clinical manifestations nor a specific cerebrospinal fluid (CSF) picture and mimics other neurological disorders leading to diagnostic dilemma. The prevalence of Neurobrucellosis ranges from 1.7 to 10% of brucellosis worldwide. This present study highlights the integrated diagnostic and clinical approaches in the diagnosis of neurobrucellosis. Cases with neurological abnormalities associated with abnormal CSF findings were included in the study. Serum and CSF samples were subjected to Rose Bengal Plate Test (RBPT), standard tube agglutination test (STAT), indirect Enzyme linked immunosorbent assay (iELISA) for IgM & IgG antibodies and polymerase chain reaction (PCR) to detect BCSP31 gene. Out of 473 cases, 278 (58.8%) were positive in serum and/or CSF by any of the methods. Out of 278, Only IgM anti-brucella antibody was positive in 105 (22.19%) cases. 122 (25.79%) cases were positive by any of the diagnostic methods in serum and not in CSF whereas 51(10.78%) cases were positive in serum and CSF and these 51 cases were considered as Neurobrucellosis among patients presenting with neurological illness. Chronic meningitis was the most common form of presentation. Multimodal differential diagnostic approaches are crucial for accurate diagnosis, effective treatment and to prevent morbidity and mortality associated with neurobrucellosis.

Clinical insights and epidemiology of central nervous system infection due to Cryptococcus neoformans/gattii species complexes: A prospective study from South India.

In the last two decades, central nervous system (CNS) cryptococcosis (CNSc) has emerged as a major opportunistic infection in the immunocompromised population of India. We have analyzed the clinical features of CNSc and epidemiology of Cryptococcus neoformans and Cryptococcus gattii. A total of 160 clinical isolates of C. neoformans/gattii recovered from CNSc patients were analyzed. The origin, clinical parameters, and imaging features of the patients were recorded, and clinical parameters were analyzed based on their human immunodeficiency virus (HIV) status and infecting species, namely, C. neoformans or C. gattii. Serotypes and mating types of the isolates were determined. Molecular typing was performed by polymerase chain reaction (PCR) fingerprinting using M13 microsatellite primer (GTG)5, and multilocus sequence typing (MLST). Majority of the patients were from Bangalore Urban, Karnataka. Among 160 cases 128 (80%) were HIV seropositive, and 32 (20%) were HIV negative. Middle-aged males (36-55 years) were highly affected. There were statistically significant differences in the clinical manifestations, imaging and CSF parameters of HIV coinfected and noninfected cases, whereas limited differences were observed in these parameters in the cases infected with C. neoformans and C. gattii. We identified 80% C. neoformans VNI, 8.75% VNII and 22.5% C. gattii (VGI), 8.75% C. tetragattii (VGIV) among clinical strains. This comprehensive study will contribute toward a better prognosis of CNS cryptococcosis patients during the hospital stay, treatment strategies for HIV coinfected and noninfected cases and will provide the molecular epidemiology of these two pathogenic fungal species in south India, which was unclear in this part of the country.

Posttraumatic movement disorders: A clinical and imaging profile of 30 patients.

BACKGROUND: Posttraumatic movement disorders (PTMDs) are frequently associated with severe head injury. There are very few studies on the clinical phenomenology and radiological correlation of PTMD. AIMS: To study the clinical phenomenology of patients with PTMD and correlate it with the site of lesion on brain imaging. MATERIALS AND METHODS: This was a prospective study of patients with suspected PTMD. All of these patients underwent neurological evaluation to characterize the phenomenology and imaging, such as computed tomography/magnetic resonance imaging (CT/MRI), to localize the site of lesion. RESULTS: The age of the patients was 32.6 ± 16.4 years and the age at onset was 29.1 ± 16.0 years. Right upper limb was the initial body part affected in 36.7% patients. Tremor (alone or with dystonia) was the most common movement disorder (MD; 44.7%) followed by parkinsonism (17.2%), dystonia (13.8%), dystonia plus (dystonia associated with choreoathetosis: 10.3%), mixed MD (more than one MD: 10.3%), and myoclonus (3.4%). MRI was performed in 23 patients and the rest seven patients underwent CT brain. Normal MRI was observed in one patient with parkinsonism. Isolated, discrete lesions were found in six (27.3%) patients. Basal ganglia was the most common site of involvement (66.7%) followed by thalamus (16.7%) and brainstem (16.7%). Diffuse white matter involvement was the most common radiological lesion in patients with tremor. CONCLUSIONS: Our study describes the clinical phenomenology of patients with PTMDs and its radiological correlation. Tremor (alone or in combination with dystonia) was the most common MD observed and diffuse white matter lesions without affection of the basal ganglia was the most common site of lesion.

Central nervous system infection due to Cryptococcus gattii sensu lato in India: Analysis of clinical features, molecular profile and antifungal susceptibility.

Cryptococcus gattii species complex has evolved as a pathogen in the last two decades causing infection among both immunocompetent and immunocompromised hosts. We aimed to analyse the clinical features of CNS infection caused by C. gattii sensu lato, molecular and antifungal susceptibility profile of this pathogen. Cases diagnosed to have CNS cryptococcosis were included in the study. Cryptococcus recovered from patient's specimen was identified by standard protocol. Species confirmation, mating type and molecular type determination were performed by PCR based methods. Antifungal susceptibility was tested in VITEK2C to amphotericin B, 5-flucytosine, fluconazole and voriconazole. Among 199 cases, 20 (10%) were due to C. gattii, comprising of 75% cryptococcal meningitis and 25% cryptococcoma cases. Young adult males were commonly affected. Headache and vomiting were prominent symptoms and 50% were immunocompromised. Among the isolates, 75%, 20% and 5% were C. tetragattii, C. gattii sensu stricto and C. bacillisporus respectively and all had mating type α. Four (20%) isolates of C. tetragattii and the only isolate of C. bacillisporus were resistant to fluconazole. The most common species isolated from south India is C. tetragattii. The study contributes to the epidemiology of C. gattii and reiterates the need for genotyping and antifungal susceptibility testing.