Sumit Singh

Low-dose topiramate versus lamotrigine in migraine prophylaxis (the Lotolamp study).

Objective.—To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo.

Major Histocompatibility Complex Class I and II Detection as a Diagnostic Tool in Idiopathic Inflammatory Myopathies

CONTEXT Muscle biopsy is at present the gold standard for the diagnosis of idiopathic inflammatory myopathies (IIMs), which include dermatomyositis, polymyositis, and inclusion body myositis. Currently, there is no definite diagnostic marker that helps in the discrimination of different subgroups of IIMs and the discrimination of IIMs from other clinical and morphologic mimics. Major histocompatibility complex (MHC) class I and II antigens are not expressed on normal muscle fibers. OBJECTIVE To determine the diagnostic utility of MHC class I and II antigen expression on the muscle biopsies from patients with various neuromuscular disorders and to validate its addition in the existing diagnostic armamentarium. DESIGN Expression of MHC class I and II antigen was studied on 126 muscle biopsies, of which 62 were IIMs and 64 were controls (taken from patients with other neuromuscular disorders). RESULTS When compared with controls, the sensitivity of MHC class I expression for diagnosis of IIMs was 88.7% (100%, 81.6%, and 100% for dermatomyositis, polymyositis, and inclusion body myositis, respectively), with a specificity of 89.1%. The specificity of MHC class II expression was 100% for all IIMs. CONCLUSION Detection of MHC class I and II antigen expression is extremely helpful in the diagnosis of IIMs and has high sensitivity and specificity, especially in dermatomyositis. This expression can be used as a diagnostic tool in discriminating IIMs from other muscle diseases in which it is either absent or weakly expressed.

Comparative efficacy of low dose, daily versus alternate day plasma exchange in severe myasthenia gravis : A randomised trial

ObjectiveTo evaluate the comparative efficacy of low dose daily versus alternate day plasma exchange in patients with severe myasthenia.MethodsThirty three patients with myasthenia gravis (Ossermans stage II b and III) were randomized to receive alternate day (n = 17) or daily low dose plasma exchange (n = 16). Plasma exchange were carried on each patient, number of exchanges varying subject to their requirements and 20-25 ml/kg plasma was removed during each session. Myasthenia gravis disease scale (MGDS) score was evaluated before and after the procedure. Time to wean off ventilator, removal of nasogastric tube and total duration of hospital stay were also assessed.ResultsThere was no statistically significant difference between daily vs. alternate day group with regards to change in MGDS score, percentage change in MGDS score, and complication rates. A decreased hospital stay was observed in patients on daily plasma exchange which almost reached statistical significance.ConclusionWe conclude from our study that daily and alternate day plasma exchange are similar in their efficacy and complication rates, however the daily schedule could be a preferred modality due to decreased hospital stay.

Diagnostic utility of skin biopsy in dystrophinopathies

AIMS Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy. METHODS Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Beckers muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies. RESULTS Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%). CONCLUSION Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy.

Limb girdle muscular dystrophy type 2A in India: A study based on semi-quantitative protein analysis, with clinical and histopathological correlation

BACKGROUND Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutation in the gene encoding for calpain-3 resulting in total or partial loss of protein. Diagnosis of LGMD2A, the most prevalent form of LGMD, is established by analyzing calpain-3 protein deficiency or CAPN3 gene mutation. Since there is no data from India regarding the incidence of LGMD2A, this study was undertaken. AIMS To study the frequency of LGMD2A in Indian population on the basis of protein analysis by immunoblotting and to correlate pathological and clinical features with protein analysis. SETTINGS AND DESIGN One hundred and seventy-one muscle biopsies of clinically suspected LGMD, unclassified muscular dystrophy or myopathy were analyzed in a tertiary national referral centre for neurosciences. Materials and Methods : Histopathological, immunohistochemical and enzyme histochemical analysis of muscle biopsies was performed followed by protein analysis for calpain-3 and dysferlin by immunoblotting. RESULTS Immunoblot identified 75 patients (43.8%) with calpain-3 deficiency, of which 36 (45%) had complete loss and 39 (55%) had partial loss of calpain-3 protein. In patients with LGMD phenotype alone, the incidence of LGMD2A was 47%. The biopsies of these patients displayed variety of morphological changes ranging from dystrophic pattern with presence of active fibre necrosis, regeneration and lobulated fibres to end stage muscle disease. The mean age of presentation and disease onset was 24 and 18 years respectively. CONCLUSIONS This series of 75 patients is probably the first confirmed cases of LGMD2A (calpainopathy) from India. Our study suggests that LGMD2A is the most frequent form of LGMD in India, similar to the Western data, thus, highlighting the importance of immunoblotting for an accurate diagnosis.

RBD in Parkinson's disease: A clinical case control study from North India

OBJECTIVES Sleep related complaints and rapid eye movement (REM) behavior disorder (RBD) are commonly reported in patients with Parkinsons disease (PD). The study aimed to compare the characteristics of patients with PD with RBD versus those without RBD. METHODS Consecutive patients with PD were evaluated with detailed clinical history, examination and questionnaire on sleep RBD over a two year period. Clinical scores included Unified Parkinsons Disease Rating Scale (UPDRS), Hoehn & Yahr Stage (H & Y), Schwab and England (S & E) scale, Mini Mental Status Examination (MMSE), EuroQol, Parkinsons disease Sleep Scale (PDSS) and Epworth Sleep Scale (ESS). The qualitative data was analyzed using chi square/Fischers exact test and continuous variables were analyzed using Students t-test. RESULTS The study included a total of 134 patients. RBD was present in 26 (19.4%) patients. There was increased occurrence of hallucinations in patients with RBD. None of the patients had familial PD. Patients with RBD had significantly higher prevalence of insomnia, nocturnal awakening, early morning awakenings and snoring. Most clinical events were brief and confined to vocalization or limb movements. CONCLUSION RBD may precede or follow PD onset. RBD has association with higher occurrence of hallucinations and other nocturnal problems; although most of these episodes were brief, had static course and were not associated with violent behavior.

Study of DSM-IV Axis I psychiatric disorders in patients with refractory complex partial seizures using a short structured clinical interview

Psychiatric disorders are a source of significant comorbidity in patients with refractory epilepsy, yet are often underrecognized. We assessed the prevalence of DSM-IV Axis I psychiatric disorders using a short structured clinical interview (Mini-International Psychiatric Interview [MINI]) in patients with medically refractory complex partial seizures. Consecutive patients with refractory epilepsy being evaluated with video/EEG monitoring and imaging for seizure focus localization and lateralization underwent MINI evaluation to assess for the presence of psychiatric disorders. Among 117 patients (74 male, 43 female) studied, 57 (48.7%) had at least one psychiatric disorder; 19 (16.2%) had depression, 10 (8.5%) dysthymia, 27 (23.0%) anxiety disorder, and 11(9.4%) other disorders. Most clinical features and epilepsy-related variables had no significant association with psychiatric disorder on logistic regression analysis. Almost half of the patients with refractory focal seizures have a coexistent psychiatric disorder, and its presence or absence cannot be predicted by their clinical profiles. All patients should be assessed and treated for psychiatric comorbidity to improve overall quality of life.

Functional mapping in PD and PSP for sustained phonation and phoneme tasks

AIM To elucidate the central basis of articulatory speech disorders in Parkinsonian syndromes using functional magnetic resonance imaging (fMRI). METHODS Twenty-two patients with Parkinsons disease (PD) and 18 with progressive supranuclear palsy (PSP) were clinically evaluated for speech dysfunction. Functional magnetic resonance imaging (fMRI) was carried out in these patients using sustained phonation and phoneme tasks. Individual and group analysis using SPM2 was done for eight patients with PD, 7 with PSP and 6 healthy controls. SETTING Tertiary Medical Teaching Institute. RESULTS For sustained phonation paradigm, superior temporal gyrus area was activated in PD patients, and occipital cortex in PSP subjects in comparison to controls. For phoneme paradigm, the patients with PD recruit lingual gyrus obviating the need for more efforts for the task. Also wider areas as well as more clusters were activated in PD patients compared to controls. Lingual gyrus was found to be strongly activated in PSP patients. Reduced activation of the primary areas with recruitment of remote areas was another prominent finding in PSP. Due to excessive motion (>1.5 mm, >1 degrees ) in all the MSA patients, they could not be considered for analysis. CONCLUSION The failure of the executive fronto-striatal network would lead to increased activation of other areas in PD, but in PSP, there is a widespread cortical dysfunction.

Fungal granuloma of the brain caused by Cladosporium bantianum--a case report and review of literature.

Involvement of the brain by neurotropic, dematiaceous fungi namely Cladosporium bantianum is extremely rare. The disease is very resistant to treatment and prone for frequent relapses despite treatment with amphotericin B and flucytosine, the drugs of choice for the infection. Surgery is often required for resection of the fungal granuloma. Isolation of the fungus from the tissue specimens and its culture, showing dark colored fungal colonies clinches the diagnosis. Animal inoculation studies can provide insights to the portal of entry of the organism. We hereby report a case of fungal granuloma of the brain due to C. bantianum, which responded favorably to intensive antifungal treatment alone, with relevant review of literature.

Cardiovascular and sudomotor autonomic dysfunction in Wilson's disease--limited correlation with clinical severity.

BACKGROUND Wilsons disease, a disorder of copper metabolism, results in abnormal accumulation of copper in liver, brain, kidney and cornea giving rise to protean manifestations. Wilsons disease predominantly affects the basal ganglia and brain stem nuclei which may cause autonomic dysfunction. Disturbances of autonomic nervous system have not received attention in Wilsons disease due to its rarity. The aim of this study was to evaluate autonomic cardiovascular reflexes in patients of Wilsons disease and to look for any relationship between autonomic nervous system disturbances and clinical severity of Wilsons disease. MATERIALS AND METHODS Cardiovascular autonomic reflexes were evaluated clinically and electrophysiologically in 30 patients of Wilsons disease with neurological onset and compared with equal number of age and gender matched healthy controls. RESULTS Significantly abnormal response to the Valsalva maneuver and RR interval variation was seen in patients compared to controls (p<0.05). Latency for sympathetic skin response was also significantly (p<0.02) prolonged in patient group. No specific correlation with clinical severity of Wilsons disease and autonomic dysfunction could be established. CONCLUSION Autonomic dysfunction occurs in Wilsons disease and affects parasympathetic more than the sympathetic functions.