Quantitative profiling and identification of differentially expressed plasma proteins in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive ataxia, characterized by progressive gait ataxia, limb ataxia, dysarthria, and areflexia associated with diabetes and hypertrophic cardiomyopathy. The primary cause of FRDA is the presence of expanded DNA triplet (GAA) repeats in the first intron of the fxn gene on chromosome 9q13. The expanded DNA repeats in fxn inhibit expression of the protein frataxin, which leads to neuronal degeneration. The aim of the study was to identify differentially expressed plasma proteins in FRDA patients for their diagnostic/prognostic applications. Clinically suspected FRDA patients (n = 42) were assessed on the International Co-Operative Ataxia Rating Scale (ICARS), and genetic confirmation was performed by analyzing (GAA) repeats via PCR. Eighteen patients were confirmed to be homozygous for FRDA, with ICARS scores of 40 ± 8. Plasma proteomics of homozygous FRDA patients and age- and gender-matched healthy controls was done using two-dimensional difference in-gel electrophoresis and LC-MS/MS. Quantitative proteomic analysis (fold change ≥1.5; P < 0.05) revealed 13 differentially expressed protein spots. These proteins were found to be associated with neuropathy (α1-antitrypsin), ataxia (apolipoprotein A-I), oxidative stress (albumin), altered lipid metabolism (apolipoprotein C-II, C-III), etc. Further investigations of these differentially expressed proteins can aid in identifying prognostic/diagnostic markers for FRDA.

Applicability of the new ILAE classification for epilepsies (2010) in persons with epilepsy at a tertiary care center in India.

PURPOSE: To test the applicability of the new International League Against Epilepsy (ILAE) 2010 classification for epilepsies and to compare it with the ILAE 1989 classification and the ILAE 2001 diagnostic scheme in developing countries with limited resources such as India. METHODS: Prospective data of 500 consecutive patients with epilepsy, presenting in neurology department of All India Institute of Medical Sciences, was collected from January 2011 to June 2012 and analyzed according to the three systems proposed by ILAE in 1989, 2001, and 2010. KEY FINDINGS: All 500 patients could be classified in the ILAE 1989 classification system, but only 413 in the ILAE 2001 diagnostic scheme (in axes 3 and 4) and 420 in the ILAE 2010 classification system. Leading categories were localization-related epilepsies, symptomatic focal epilepsies, perinatal insult, and epilepsies attributed to structural and metabolic cause in ILAE 1989, 2001 axis 3, 2001 axis 4, and 2010 systems, respectively. The ILAE 1989 classification system could categorize significantly greater numbers of patients compared to the 2001 and 2010 systems, whereas the latter two remained similar. SIGNIFICANCE: A large group of patients remained unclassified in the new classification system despite our tremendous gain in knowledge through improved imaging, genomics, and molecular biology, and so on, which could be attributed to lack of availability of facilities in developing countries. Dichotomy of localization-related and generalized epilepsy still makes for a fundamental and pragmatic working diagnosis and guides the physician about the extent of investigations and treatment especially in "epilepsies of unknown cause."

Quantitative profiling and identification of plasma proteins of spinocerebellar ataxia type 2 patients.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an autosomal-dominant hereditary ataxia characterized by progressive gait and limb ataxia, dysarthria, slow saccades, neuropathy and dementia. The expansion of trinucleotide CAG repeats in the coding region of the ATXN-2 gene leads to expanded polyglutamine stretch in the mutated protein which causes neuronal death. OBJECTIVE: In this study, we investigated the blood plasma of SCA2 patients to find protein biomarkers. METHODS: Thirty-two ataxia patients clinically suspected for SCA2 were evaluated by the International Co-operative Ataxia Rating Scale followed by genetic analysis using PCR. Plasma proteomics of SCA2 patients and age- and gender-matched healthy controls was done using 2D-difference in-gel electrophoresis, LC-MS/MS and Western blot. RESULTS: Genetic analysis confirmed 10 of 32 suspected SCA2 patients. Proteomic data revealed nine differentially expressed proteins in SCA2. These proteins find good association with oxidative stress, calcium-dependent apoptosis, neuropathy, and cognitive impairment in SCA2 patients. Interestingly, the elevated levels of the voltage-dependent calcium channel γ-3 subunit showed a direct correlation with calcium-generated apoptosis of Purkinje cells. The cognitive deficit, a common symptom in SCA2 patients, seems to correlate with decreased levels of transthyretin and retinol-binding protein-4. CONCLUSIONS: Some of these identified proteins in SCA2 can be useful for therapeutic, diagnostic and prognostic purposes.

A prospective study of in-hospital mortality and discharge outcome in spontaneous intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity. Various clinical and imaging predictors of mortality have been observed in previous studies. AIMS: To study factors associated with in-hospital mortality in patients with ICH and observe the disability status of patients [assessed by modified Rankin scale (mRS)] at the time of discharge. DESIGN: Prospective observational study. MATERIALS AND METHODS: All consecutive patients with acute hypertensive ICH admitted during the study period were enrolled. Data recorded included: Demographics, clinical, biochemical and cranial computed tomography (CT) findings. Primary outcome was defined as either death or survival within the hospital. mRS was used to assess outcome at discharge. RESULTS: Of the total 214 patients with ICH (193 supratentorial and 21 infratentorial), 70 (32.7%) patients died during the hospital stay. On bivariate analysis, low Glasgow Coma Scale (GCS) score, ventilatory assistance, higher hematoma volume, midline shift, hydrocephalus and intraventricular hematoma (IVH) were associated with mortality. ICH grading scale (ICH-GS) and ICH scores were higher in patients who died (P < 0.0001). Ninety-five (44.6%) patients underwent a neurosurgical intervention; 66 (45.8%) patients among the survivors compared with 29 (41.4%) among those who died (P = 0.54, Odds Ratio (OR) 0.83, 95% Confidence Interval (CI) 0.46-1.48). Independent predictors of mortality included a higher baseline hematoma volume ( P = 0.04 OR 1.01, 95% CI 1.00-1.02), lower GCS ( P = 0.01 OR 2.57, 95%CI 1.25-5.29), intraventricular extension of hematoma ( P = 0.007 OR 2.66, 95% CI 1.26-5.56) and ventilatory requirement (P < 0.0001 OR 8.34, 95%CI 2.75-25.38). Among survivors (n = 144), most were disabled [mRS 0-3, 7 (4.8%) and mRS 4-5, 137 (95.13%)] at discharge. CONCLUSIONS: Low GCS, higher baseline ICH volume, presence of IVH and need for ventilatory assistance are independent predictors of mortality. Most of the patients at discharge were disabled. Surgery did not improve mortality or outcome.

Complications in acute stroke in India (CAST-I): a multicenter study.

The prognosis and final outcome in patients who sustain stroke are significantly affected by medical complications occurring during the acute phase of stroke. Only limited information is available from India and other developing countries regarding acute complications of stroke. This study examined the frequency of acute stroke and the factors associated with complications of stroke in India. In this prospective multicenter study, running from March 2008 to September 2009, 6 hospitals collected information on complications of first-ever stroke during admission. Complications were defined in accordance with standard criteria. Outcome at 30 days poststroke was assessed using the modified Rankin Scale. Stroke characteristics, length of hospital stay, and stroke severity (based on the National Institutes of Health Stroke Scale) were documented. Hematologic (ie, hemoglobin) and biochemical (ie, total proteins and albumin) parameters also were obtained. A total of 449 patients out of the recruited 476 completed follow-up. The mean age was 58.1 ± 13.7 years (range, 16-96 years), and the majority were men (n = 282; 62.8%). The mean National Institutes of Stroke Scale score was 10.2 ± 5.3. Overall, 206 patients (45.9%) experienced complications during admission. In the logistic regression analysis, limb weakness (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.02-0.67; P = .01), anemia (OR, 0.35; 95% CI, 0.15-0.81; P = .01), length of hospital stay (OR, 0.89; 95% CI, 0.85-0.94; P < .0001), and stroke severity (OR, 0.27; 95% CI, 0.10-0.72; P = .01) were the variables associated with complications. Such complications as urinary tract infection (OR, 0.31; 95% CI, 0.13-0.78; P = .01), chest infection (OR, 1.81; 95% CI, 1.12-2.93; P = .02), bedsores (OR, 3.52; 95% CI, 1.02-12.08; P = .05), other pain (OR, 0.21; 95% CI, 0.09-0.49; P < .0001), and depression (OR, 2.22; 95% CI, 1.30-3.80; P < .01) were associated with poor outcome. Our study shows high rates of complication in acute stroke. Limb weakness, stroke severity, length of hospital stay, and anemia were the factors associated with complications. Other complications, such as urinary tract infection, chest infection, bedsores, other pain, and depression, can lead to poor outcome.

Isolated facial myokymia as a presenting feature of pontine neurocysticercosis.

A 45-year-old healthy man presented with 2 weeks history of continuous rippling and quivering movements of his right side of face and neck suggestive of myokymia. MRI scan of the head revealed neurocysticercus in the pons. Treatment with steroids and carbamezapine produced a significant benefit. This is the first report of pontine neurocysticercosis presenting as an isolated facial myokymia.

Psychosocial impact of epilepsy in women of childbearing age in India.

The aim was to evaluate comprehensively the psychosocial impact of epilepsy in women between 15-40 years of age with epilepsy, compared to those with migraine and healthy, pregnant women. One hundred women with epilepsy, 50 with migraine and 100 healthy, pregnant women were enrolled over a two-year period. The three groups were assessed using questionnaires for quality of life (QOL), coping strategies and caregiver burden. The influence of demographic and seizure variables on these psychosocial outcomes were also assessed.It was found that quality of life was least, and the burden experienced by the caregiver was significantly more in patients with epilepsy (p < 0.001). Women with epilepsy relied more on religion/faith as a coping method (p = 0.021), and less on problem solving strategies (p < 0.001) when compared to those with migraine. When compared to healthy, pregnant women, they more frequently employed religious methods of coping and denial (p < 0.001), with significantly less use of problem solving techniques, acceptance, and positive and negative distraction(p < 0.001). Less frequent seizures, better education and remission sustained for at least six months, were associated with better QOL. Educational status, frequency of seizures and time elapsed since last seizure emerged as significant determinants of coping behaviour. Low educational status and monthly income of the family contributed significantly to caregiver burden.This study helped to identify the different areas of psychosocial impairment in patients with epilepsy, as well as the contributing factors. Women with epilepsy rarely used constructive coping strategies, and this was found to contribute to their poor psychosocial status and adjustment within the family and society at large.

Functional imaging in Lhermitte-Duclose disease.

PURPOSE: A comprehensive metabolic characterization of a patient with dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos Disease (LDD) is presented. PROCEDURES: Assessment using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), carbon-11-labeled methionine (11C-MET), carbon-11-labeled choline (11C-Choline) positron emission tomography (PET), and 1H-proton magnetic resonance spectroscopy (MRS) was carried out in a 30-year-old Caucasian woman. RESULTS: FDG-PET revealed hypermetabolism of the tumor. 11C-MET-PET revealed moderate uptake and 11C-Choline showed no uptake. 1H-MRS demonstrated an elevated level of lactate and decreased levels of choline (Cho) and myoinositol. CONCLUSION: Functional imaging in LDD reflects the dual pathological features of neoplasm and hamartoma.

Primary angiitis of the central nervous system: a study of histopathological patterns and review of the literature.

Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis of unknown aetiology. Multifaceted clinical manifestations, non-specific MRI findings, a broad range of differential diagnoses and diverse pathological appearances prove to be a diagnostic challenge. However, a prompt diagnosis and aggressive treatment are crucial to avoid permanent damage. Hence, we present the clinico-pathological spectrum of this entity and highlight the limitations of currently available diagnostic modalities. We describe in detail the histopathological findings of eight cases of PACNS diagnosed at the Department of Pathology, AIIMS, over a period of eight years. Eight cases of PACNS were identified during this period. Five cases (62.5%) showed features of granulomatous vasculitis, two (25%) showed lymphocytic vasculitis and one case (12.5%) showed a predominantly necrotizing pattern of vasculitis. Diagnosis of PACNS is a challenge and requires a high index of clinical suspicion. Appropriate work-up to exclude other conditions is mandatory. Brain biopsy is useful in making the diagnosis and ruling out mimicking conditions.

Quantification of circulating plasma DNA in Friedreich's ataxia and spinocerebellar ataxia types 2 and 12.

DNA triplet repeat expansion-associated ataxias, Friedreich's ataxia, and different types of spinocerebellar ataxias (SCAs) are progressive multisystem neurodegenerative disorders. The diagnosis of this wide group of inherited ataxias is essentially based on clinical findings. Cell-free circulating DNA in plasma has been considered as a powerful tool in clinical diagnosis and prognosis of several human diseases. In the present study, clinically suspected patients were assessed on the International Co-operative Ataxia Rating Scale and further confirmed by molecular analysis of DNA triplet repeats. Quantification of plasma DNA using a highly sensitive and DNA-specific PicoGreen fluorescent assay was done. We found significantly high levels (p < 0.001) of plasma DNA of 167 ± 43 ng/mL in Friedreich's ataxia patients (n = 15), 148 ± 29 ng/mL in SCA2 patients (n = 10), and 137 ± 29 ng/mL in SCA12 patients (n = 25), whereas those of healthy controls (n = 20) was only 59 ± 15 ng/mL. Therefore, we were able to distinguish between ataxia patients and healthy controls using plasma DNA. Although the precise mechanism by which plasma DNA enters into circulation is not known, significantly higher concentrations of plasma DNA appears to be due to neuronal and muscular degeneration in these patients. Identification of genes in plasma DNA, which are overexpressed or novel, can be a promising tool for the prognosis of these diseases.