Idiopathic Intracranial Hypertension - Challenges and Pearls.

Idiopathic intracranial hypertension (IIH) is defined as a syndrome of raised intracranial pressure with normal imaging of the brain and cerebrospinal fluid (CSF) composition. There is a rising incidence and prevalence of this disease related to the increased prevalence of obesity. It typically affects women of working age, and headache is the predominant morbidity in over 90%. The disease is also more prevalent in young males. There are many controversies and myths that surround IIH. There are currently few treatment options for IIH, management is typically medical with those experiencing progressive visual loss undergoing surgical procedures. Weight loss and venous sinus stenting are a few therapies directed at the etiology.

Vasculitic Neuropathy: A Retrospective Analysis of Nerve Biopsies and Clinical Features from a Single Tertiary Care Center.

OBJECTIVE: Vasculitic neuropathy can be either restricted to the peripheral nerves or associated with systemic involvement of other organs. The objective of this study was to analyze the nerve biopsies reported as "vasculitic neuropathy" with clinical features. MATERIALS AND METHODS: All cases diagnosed with vasculitic neuropathy were retrospectively analyzed and categorized as systemic vasculitis and nonsystemic vasculitic neuropathy based on the clinical features. The histological features were further evaluated and classified according to the Peripheral Nerve Society Guidelines. RESULTS: Of the 126 cases, there were 65 nonsystemic vasculitis, 45 secondary systemic vasculitis, and 16 primary systemic vasculitis. Definite vasculitis was more common in the systemic vasculitis group. The epineurial vessels were predominantly involved with chronic axonal changes. CONCLUSION: The sensitivity of definite vasculitis on nerve biopsy was 54.76%. The sensitivity increases when the diagnostic criteria of definite and probable vasculitis were applied taking into account perivascular inflammation accompanied by vascular changes and axonopathy.

Comparative Effects of Education and Bilingualism on the Onset of Mild Cognitive Impairment.

BACKGROUND: Increasing evidence suggests that life course factors such as education and bilingualism may have a protective role against dementia due to Alzheimer disease. This study aimed to compare the effects of education and bilingualism on the onset of cognitive decline at the stage of mild cognitive impairment (MCI). METHODS: A total of 115 patients with MCI evaluated in a specialty memory clinic in Hyderabad, India, formed the cohort. MCI was diagnosed according to Petersen's criteria following clinical evaluation and brain imaging. Age at onset of MCI was compared between bilinguals and monolinguals, and across subjects with high and low levels of education, adjusting for possible confounding variables. RESULTS: The bilingual MCI patients were found to have a clinical onset of cognitive complaints 7.4 years later than monolinguals (65.2 vs. 58.1 years; p = 0.004), while years of education was not associated with delayed onset (1-10 years of education, 59.1 years; 11-15 years of education, 62.6 years; >15 years of education, 62.2 years; p = 0.426). CONCLUSION: The effect of bilingualism is protective against cognitive decline, and lies along a continuum from normal to pathological states. In comparison, the role of years of education is less robust.

Anti-ganglioside antibodies profile in Guillain-Barré syndrome: Correlation with clinical features, electrophysiological pattern, and outcome.

BACKGROUND: Guillain-Barré syndrome (GBS) and its subtypes are associated with distinct anti-ganglioside antibodies. Hence, we aimed to determine the frequency of anti-ganglioside antibodies and its correlation with clinical features, electrophysiological patterns, and outcome in patients with GBS. MATERIAL AND METHODS: The data regarding clinical features, electrophysiological patterns, and outcome at 6 months were collected and analyzed from the case records of patients diagnosed with GBS during 2008-2013 at a tertiary care hospital in south India. RESULTS: A total of 204 patients with GBS were studied, and 73 patients (mean age: 37.6 ± 17.5 years) who underwent anti-ganglioside antibody testing were analyzed. Male-to-female ratio was 2.5:1. IgG anti-ganglioside antibodies were positive in 41/73 patients. The most common IgG anti-ganglioside antibody observed in the acute demyelinating variant was anti-GT1b (n = 13; 17.8%), and, those in the acute axonal variant were anti-GM1, anti-GM2, anti-GD1b, and anti-GT1b antibodies (n = 9;12.3% each). Three patients died and 5 patients were unable to walk independently at the end of 6 months. CONCLUSIONS: The frequency of anti-ganglioside antibodies in our cohort with GBS was 56%, with IgG anti-GT1b antibody being the most common. The anti-ganglioside antibodies were significantly positive in acute motor axonal neuropathy (AMAN) subtype of GBS. The presence of anti-ganglioside antibodies was not found to be of significant use in predicting the outcome. Although it was observed that the absence, and not the presence, of anti-ganglioside antibodies was associated with antecedent infection, dysautonomia, and requirement of ventilator support, the overall disease severity was not antibody dependant.

A prospective study of diffusion weighted magnetic resonance imaging abnormalities in patients with cluster of seizures and status epilepticus.

OBJECTIVE: To study the frequency, imaging characteristics, and clinical predictors for development of periictal diffusion weighted MRI abnormalities. METHODS: We prospectively analyzed electro clinical and imaging characteristic of adult patients with cluster of seizures or status epilepticus between November 2013 and November 2015, in whom the diffusion weighted imaging was done within 24h after the end of last seizure (clinical or electrographic). RESULTS: There were thirty patients who fulfilled the inclusion and exclusion criteria. Twenty patients (66%) had periictal MRI abnormalities. Nine patients (34%) did not have any MRI abnormality. All the patients with PMA had abnormalities on diffusion weighted imaging (DWI). Hippocampal abnormalities were seen in nine (53%), perisylvian in two (11.7%), thalamic in five (30%), splenium involvement in two (11.7%) and cortical involvement (temporo-occipital, parieto-occipital, temporo-parietal, fronto-parietal and fronto-temporal) in sixteen (94.1%) patients. Complete reversal of DWI changes was noted in sixteen (80%) patients and four (20%) patients showed partial resolution of MRI abnormalities. Mean duration of seizures was significantly higher among patients with PMA (59.11+20.97h) compared to those without MRI changes (27.33+9.33h) (p<0.001). CONCLUSIONS: Diffusion abnormalities on MRI are common in patients with cluster of seizures and status epilepticus and were highly concordant with clinical semiology and EEG activity. Patients with longer duration of seizures/status were more likely to have PMA.

Comparative analysis of four disease prediction models of Parkinson's disease.

Parkinson's disease (PD) is a multi-factorial disorder with high-penetrant mutations accounting for small percentage of PD. Our previous studies demonstrated individual association of genetic variants in folate, xenobiotic, and dopamine metabolic pathways with PD risk. The rational of the study was to develop a risk prediction model for PD using these genetic polymorphisms along with synuclein (SNCA) polymorphism. We have generated additive, multifactor dimensionality reduction (MDR), recursive partitioning (RP), and artificial neural network (ANN) models using 21 SNPs as inputs and disease outcome as output. The clinical utility of all these models was assessed by plotting receiver operating characteristics curves where in area under the curve (AUC) was used as an index of diagnostic utility of the model. The additive model was the simplest and exhibited an AUC of 0.72. The MDR model showed significant gene-gene interactions between SNCA, DRD4VNTR, and DRD2A polymorphisms. The RP model showed SHMT C1420T as important determinant of PD risk. This variant allele was found to be protective and this protection was nullified by MTRR A66G. Inheritance of SHMT wild allele and SNCA intronic polymorphism was shown to increase the risk of PD. The ANN model showed higher diagnostic utility (AUC = 0.86) compared to all the models and was able to explain 56.6% cases of sporadic PD. To conclude, the ANN model developed using SNPs in folate, xenobiotic, and dopamine pathways along with SNCA has higher clinical utility in predicting PD risk compared to other models.

Prevalence and risk factors of carotid intima-media thickness in asymptomatic individual subjects in a tertiary care center in India.

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

Association of Parkinson's disease with altered serum levels of lead and transition metals among South Indian subjects.

Several epidemiologic studies have suggested an association between the Parkinson's disease (PD) and exposure to heavy metals, such as lead, iron, copper, manganese, etc. A growing body of evidence suggests that heavy metals stimulate free radical formation in the brain and can lead to neurodegeneration. In the present study, we investigated whether such association exists in PD cases from rural and urban areas in our study population. The plasma levels of copper, iron, manganese and lead in PD cases (n = 150) and controls (n = 170) were determined by inductively coupled plasma mass spectrometry (ICP-MS) and correlated with the oxidative stress markers like malondialdehyde (MDA), protein carbonyl and total glutathione. Results indicated significant increase in the levels of copper (17.73 +/- 4.48 vs. 13.0 + 3.22 ng/ml) and iron (554.4 +/- 123.8 vs. 421.7 +/- 126.1 ng/ml) in PD cases compared to controls, whereas no significant differences in the levels of manganese and lead were observed. Further, the data based on urban or rural residence showed that plasma copper, iron, manganese levels were comparatively higher in rural subjects, whereas plasma lead levels were significantly higher in urban subjects. Increased plasma iron showed positive correlation with marker of lipid peroxidation (MDA), suggesting that increased iron levels induced oxidative stress in PD. These results substantiated the earlier observations about the role of environmental exposure and metal-induced oxidative stress in the etiology of PD.

Association of seven functional polymorphisms of one-carbon metabolic pathway with total plasma homocysteine levels and susceptibility to Parkinson's disease among South Indians.

This study from South India was performed to ascertain the impact of seven functional polymorphisms of one-carbon metabolic pathway on total plasma homocysteine levels and susceptibility to PD. A total of 151 cases of Parkinson's disease and 416 healthy controls were analyzed for fasting plasma homocysteine levels by reverse phase HPLC. PCR-RFLP approaches were used to analyze glutamate carboxypeptidase II (GCPII) 1561 C>T, reduced folate carrier 1 (RFC1) 80 G>A, cytosolic serine hydroxymethyl transferase (cSHMT) 1420 C>T, methylene tetrahydrofolate reductase (MTHFR) 677 C>T, methionine synthase (MTR) 2756 A>G and methionine synthase reductase (MTRR) 66 A>G polymorphisms. PCR-AFLP was used for the analysis of thymidylate synthase (TYMS) 5'-UTR 28bp tandem repeat. PD cases exhibited elevated plasma homocysteine levels compared to controls (men: 28.8 ± 6.9 vs. 16.4 ± 8.8 µmol/L; women: 25.4 ± 5.3 vs. 11.2 ± 5.1µmol/L). Homocysteine levels showed positive correlation with male gender (r=0.39, p<0.0001) and MTRR 66 A>G (r=0.31, p<0.0001) whereas an inverse correlation was observed with cSHMT 1420 C>T polymorphism. MTRR 66 A>G polymorphism showed independent risk for PD (OR: 3.42, 95% CI: 2.35-4.98) whereas cSHMT 1420 C>T conferred protection against PD (OR: 0.11, 95% CI: 0.07-0.17). Multifactor dimensionality reduction analysis showed synergistic interactions between MTHFR 677 C>T and MTRR 66 A>G, whereas cSHMT 1420 C>T exhibited counteracting interactions in altering susceptibility to PD. To conclude, PD cases exhibited hyperhomocysteinemia and MTRR 66 A>G and cSHMT 1420 C>T gene variants were shown to modulate PD risk by altering the homocysteine levels.

Sexual dimorphism in xenobiotic genetic variants-mediated risk for Parkinson's disease.

The vulnerability of dopaminergic neurons to environmental exposures in sporadic Parkinson's disease (PD) has been attributed to altered detoxification by xenobiotic metabolizing genes. Hence, we investigated the influence of genetic polymorphisms in xenobiotic metabolic pathway (CYP1A1 m1, CYP1A1 m2, CYP1A1 m4, COMT p.H108L, GSTT1, and GSTM1) on the susceptibility to PD. We used PCR-RFLP for CYP1A1 and COMT genotyping; multiplex-PCR for GSTT1 and GSTM1 deletion analysis; and spectrophotometric methods to evaluate the oxidative stress markers. Results showed association of CYP1A1 m1 (OR: 2.38, 95 % CI: 1.76-3.22) and COMT p.H108L (OR: 2.08 95 % CI: 1.56-2.77) polymorphisms with risk for PD. Male patients carrying combination of COMT p.H108L and CYP1A1 m1 variant alleles showed an early onset of the disease. There was a significant increase in oxidative stress makers such as malondialdehyde and protein carbonyls; and decrease in glutathione levels in PD cases compared to controls (P < 0.05). To conclude, CYP1A1 m1, COMT p.H108L polymorphisms were associated with PD risk, and sexual dimorphism was observed in these associations.

Guillain Barre syndrome as a manifestation of neurological melioidosis.

Neurological melioidosis is a very rare and very few cases have been reported from India. Presentation is an extremely varied and as this disease is associated with high mortality, high index of suspicion is needed to diagnose and treat. In this context, we report a patient presenting as Guillain Barre syndrome evaluated as melioidosis.

Incidence of malignancies in biopsy-proven inflammatory myopathy.

BACKGROUND: Inflammatory myopathy (IM) as a manifestation of paraneoplastic syndrome has been well-documented. However, the prevalence of malignancies reported varies across the studies. There are very few studies reported from Asia, only one from India. AIM: The aim of this analysis was to study the prevalence of malignancy in biopsy-proven cases of IM in India and to study the difference between malignant and non-malignant groups. MATERIALS AND METHODS: The study was a retrospective review of case records of patients with a biopsy-proven IM attending Tertiary Care University Hospital. RESULTS: Of the total 86 patients with biopsy-proven IM, 22 patients were polymyositis, 63 patients had dermatomyositis (DM) and one was with an inclusion body myositis, not included for further analysis. Associated malignancy was diagnosed in 6 (7%) patients, and five of them were females. Diagnosis of associated malignancy was identified at the time of diagnosis of IM in four (66.7%) patients. All the six patients with an associated malignancy had DM. Only one patient died within 1 year of diagnosis. Creatinine kinase was much lower in patients with malignancy associated IM than in patients with no malignancy (P < 0.0001). CONCLUSION: The prevalence of malignancy was very low in our cohort as compared to the studies from other countries. Breast cancer was the most common malignancy associated with DM. The type of associated malignancy was quite variable.

Cerebral glucose metabolism, clinical, neuropsychological, and radiological profile in patients with corticobasal syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is characterized by progressive asymmetric rigidity and localized cortical disorders namely apraxia, cortical, sensory loss, focal dystonia, and refractory to levodopa treatment. AIM: To study the cerebral glucose-metabolism, cognitive, and magnetic resonance imaging (MRI) features in patients with CBS. MATERIALS AND METHODS: Seventeen consecutive patients with CBS who fulfilled the criteria proposed by Lang et al., were studied. A detailed neurological including higher cortical functions and Unified Parkinson's Disease Rating Scale (UPDRS) on and off motor scores and neuropsychological assessment were done. All patients except one had undergone MRI brain and 18-Flouro 5-Deoxy Glucose Positron Emission Tomography (FDG PET CT) brain scan for assessing cortical atrophy and cerebral glucose metabolism, respectively. RESULTS: Most of the 17 patients had Parkinsonian features with focal cortical signs of dystonia, apraxia, and cortical sensory loss and the hypokinesia was predominantly on left side. Neuropsychological assessment had shown impairment of frontal executive function, visuospatial function, and language. MRI brain showed asymmetrical cortical atrophy in left temparoparietal areas and basal ganglia. The MRI findings correlated with FDG PET brain scan findings, asymmetric focal hypometabolism in basal ganglia and inferior parietal and temporal, frontal lobes. CONCLUSION: 18 FDG PET brain is more sensitive than MRI brain in the early diagnosis of CBS and also correlates well with neuropsychological assessment.

Impact of COMT H108L, MAOB int 13 A>G and DRD2 haplotype on the susceptibility to Parkinson's disease in South Indian subjects.

In view of documented evidence demonstrating the association of dopaminergic metabolism and neurotransmission with Parkinson's disease (PD), a case-control study was conducted to investigate the impact of particular polymorphisms in the catechol O-methyl transferase (COMT) H108L, monoamine oxidase B (MAOB) int 13 A>G, dopamine transporter 1 (DAT1) A1215G, dopamine receptor D2 (DRD2) Taq1A, DRD2 Taq1B and DRD2 Taq1D genes on the susceptibility to PD. PCR-RFLP method was used for the genetic analysis. The COMT H108L polymorphism increased PD risk by 1.4-fold (95%CI: 1.02-1.98), whereas reduced risk was observed with MAOB int 13 A>G polymorphism (OR: 0.77, 95%CI: 0.51-0.99). Multifactor dimensionality reduction analysis showed gene-gene interactions between these two loci that resulted in loss of the protective role of MAOB G-allele in the presence of COMT L-allele. DAT1A1215G polymorphism in the exon 9 was not associated with PD. Individually, DRD2 polymorphisms showed null association. However, all-variant haplotype of DRD2 locus i.e. T-G-T haplotype showed 29.8-fold risk for PD compared to all-wild haplotype i.e., C-A-C haplotype (95%CI: 6.85-130.4). To conclude, genetic variants of COMT, MAOB and DRD2 loci modulate susceptibility to PD in South Indian subjects.

Subtypes of dementia: a study from a memory clinic in India.

BACKGROUND: The clinical syndrome of dementia consists of several subtypes that are distinct in their etiology, clinical profile, management, and outcome. Limited specialized services are available for dementia patients in India. We report the profile of dementia subtypes from a clinic-based dementia registry in India. METHODS: Consecutive dementia patients were investigated with clinical evaluation, neuropsychological tests modified for local use, and brain imaging. RESULTS: In 347 consecutive dementia patients, Alzheimer's disease was the most common subtype of dementia (38.3%), followed by a high proportion of vascular dementia (25.4%). Frontotemporal dementia syndromes were not uncommon (18.7%). Dementia with Lewy bodies was encountered in 8.9% of the patients, and mixed dementia was found in 8.6%. The mean age of the group at presentation was 66.3 years, nearly a decade younger than in developed countries. The proportion of patients with early-onset dementia was high (49.9%). CONCLUSIONS: Our results demonstrate that the clinical profiles of dementia subtypes in a clinic population are influenced by the population's demographic profile, cardiovascular risk factor burden, sociocultural attitudes about cognitive impairment, and possibly genetic factors.