Roopa Rajan

Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no effective treatment. Stem cell therapy may be one of the promising treatment options for such patients. AIM To assess the feasibility, efficacy and safety of autologous bone marrow-derived stem cells in patients of ALS. SETTINGS AND DESIGN We conducted an open-label pilot study of autologous bone marrow-derived stem cells in patients with ALS attending the Neurology Clinic of a tertiary care referral centre. MATERIALS AND METHODS Ten patients with ALS with mean revised ALS Functional Rating Scale (ALSFRS-R) score of 30.2 (± 10.58) at baseline received intrathecal autologous bone marrow-derived stem cells. Primary end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point deterioration, median survival and reported adverse events. Paired t-test was used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was used for survival calculations. RESULTS There was no significant deterioration in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090). The median survival post procedure was 18.0 months and median time to 4-point deterioration was 16.7 months. No significant adverse events were reported. CONCLUSION Autologous bone marrow-derived stem cell therapy is safe and feasible in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend towards stabilization of disease. However, the benefit needs to be confirmed in the long-term follow-up period.

Interictal cerebral and systemic endothelial dysfunction in patients with migraine: a case–control study

Background Although systemic endothelial function is unimpaired in migraine, it is unknown whether cerebral endothelial function impairment exists in migraineurs. Materials and methods We conducted a prospective study to assess endothelial function in migraineurs (n=45) and healthy volunteers (n=44). Cerebral endothelial function was assessed by Breath Holding Index (BHI) on transcranial Doppler in bilateral middle cerebral artery (MCA at 30–60 mm), posterior cerebral artery (PCA at 60–80 mm) and basilar artery (BA at 80–120 mm) using bilateral monitoring probes fixed on headband. Brachial artery flow-mediated dilation (FMD) was used as measure of systemic endothelial function. Results There was no difference in baseline mean velocities of MCA, PCA, BA among migraineurs and controls. Mean BHI was significantly lower in PCA (p<0.001) and BA (p<0.001) in patients with migraine with no difference in MCA (p=0.909, 0.450). Cerebral endothelial dysfunction (BHI<1.15) was present in 62.2% of migraineurs in the right PCA (p<0.001), 57.8% in left PCA (p<0.001) and 77.8% in BA (BHI <0.83, p<0.001). There was no difference in BHI among migraineurs without and with aura (n=15). Cerebral and systemic endothelial function had no correlation in migraineurs. Increasing BMI was identified as a predictor of impaired BHI in the BA in migraineurs (p=0.020). Age, sex, presence of aura, lateralisation of headache, headache frequency, time to last attack and impaired FMD were not associated with impaired PCA and BA BHI in migraineurs. Conclusions Migraineurs may have isolated cerebral endothelial dysfunction restricted to the posterior circulation in the absence of systemic endothelial dysfunction.

Teaching NeuroImages: Deep gray matter involvement in neurobrucellosis

A 27-year-old man, recent visitor to the Middle East, presented with 6-week history of fever (up to 102°F) followed by altered behavior and left hemiparesis. CSF was acellular with raised protein (138 mg/dL). CSF bacterial culture was sterile; adenosine deaminase normal (3 U/L); cryptococcal antigen, Venereal Disease Research Laboratory test, and Japanese B serology were negative. HIV serology and vasculitic workup were unremarkable. Serum Brucella agglutination titer was 320 IU (immunoglobulin M fraction 280 IU). Cranial MRI showed nonenhancing bilateral white matter and basal ganglia hyperintensities on T2-weighted images (figure, A–C). The patient was treated with IV ceftriaxone (1 month) along with oral doxycycline and rifampicin (4 months). At 3 months, Brucella agglutination titer was <20 IU and the patient became independent. Follow-up imaging showed a reduction in lesions (figure, D). Brucellosis frequently presents as chronic meningitis along with cranial neuropathies and spinal arachnoiditis.1 Demyelinating lesions are described in neurobrucellosis,1,2 involvement of the deep gray matter being unusual.

Validation of the consensus methodology algorithm for the classification of systemic necrotizing vasculitis in Indian patients

Many patients with systemic necrotizing vasculitis (SNV) satisfy classification criteria of different disease entities when different classification systems are used. A new classification algorithm has been proposed recently by using the American College of Rheumatology criteria, Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers for a more uniform classification of patients suffering from these rare disorders.

Prothrombotic states in migraine.

The increased risk of cardiovascular and cerebrovascular events in patients with migraine remains unexplained. Prothrombotic states are thought to contribute to this increased risk. The present study aimed to compare the prevalence of prothrombotic states in patients with migraine and headache-free controls. We conducted a case–control study to screen for prothrombotic states protein C, protein S (PS), antithrombin III, factor V Leiden, lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein 1 antibodies in 101 consecutive patients with migraine and 148 controls. An underlying prothrombotic state was encountered in 11.8% of the patients with migraine, PS deficiency being the most common (4.0%). There was no significant difference in the prevalence of prothrombotic states in patients with migraine compared to controls. Traditional prothrombotic states do not seem to have a higher prevalence in patients with migraine compared to controls.

Malignant Subthalamic Nucleus-Deep Brain Stimulation Withdrawal Syndrome in Parkinson's Disease

Abrupt cessation of STN‐DBS is an under‐recognized cause of life‐threatening akinetic crisis in Parkinsons disease (PD) and can present as a movement disorder emergency. We report on 2 patients who survived severe and prolonged akinetic crisis after abrupt cessation of STN stimulation for PD (malignant STN‐DBS withdrawal syndrome). We discuss the clinical similarities and possible differences in pathophysiology from the akinetic crisis in medically‐treated PD. Although early implantable pulse generator (IPG) replacement is the definitive treatment, medical and economic considerations may preclude early surgery and strategies for medical management assume importance. We reflect upon the socioeconomic concerns surrounding DBS in countries lacking health care coverage and the need for user‐independent monitors and indicators of low IPG battery status.

Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease-Connecting the dots in a multicomponent network

Levodopa-induced dyskinesias are motor complications following long term dopaminergic therapy in Parkinsons disease (PD). Impaired brain plasticity resulting in the creation of aberrant motor maps intended to encode normal voluntary movement is proposed to result in the development of dyskinesias. Traditionally, the various nodes in the motor network like the striato-cortical and the cerebello-thalamic loops were thought to function independent of each other with little communication among them. Anatomical evidence from primates revealed the existence of reciprocal loops between the basal ganglia and the cerebellum providing an anatomical basis for communication between the motor network loops. Dyskinetic PD patients reveal impaired brain plasticity within the motor cortex which may be modulated by cortico-cortical, cerebello-cortical or striato-cortical connections. In this article, we review the evidence for altered plasticity in the multicomponent motor network in the context of levodopa induced dyskinesias in PD. Current evidence suggests a pivotal role for the cerebellum in the larger motor network with the ability to integrate sensorimotor information and independently influence multiple nodes in this network. Targeting the cerebellum seems to be a justified approach for future interventions aimed at attenuating levodopa-induced dyskinesias.

Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease—A Computational Study

Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinsons disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the models STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients.

Acute Flaccid paralysis in adults: Our experience.

Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array of potential etiologies that vary with age. We present our experience of acute onset lower motor neuron paralysis. Materials and Methods: One hundred and thirty-three consecutive adult patients presenting with weakness of duration less than four weeks over 12 months period were enrolled. Detailed history, clinical examination, and relevant investigations according to a pre-defined diagnostic algorithm were carried out. The patients were followed through their hospital stay till discharge or death. Results: The mean age was 33.27 (range 13-89) years with male preponderance (67.7%). The most common etiology was neuroparalytic snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%), constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute intermittent porphyria (4.5%) were the other important conditions. We did not encounter any case of acute polio mylitis in adults. In-hospital mortality due to respiratory paralysis was 9%. Conclusion: Neuroparalytic snakebite and Guillain Barre syndrome were the most common causes of acute flaccid paralysis in adults in our study.

Facial nuclear degeneration on MRI in bulbar onset amyotrophic lateral sclerosis.

A 45-year-old male presented with progressive dysarthria and dysphagia for 1 year. Examination revealed bilateral facial (Figure 1A) and neck flexor weakness, with depressed gag and tongue fasciculations. Fasciculations, wasting and brisk reflexes were noted in upper limbs. Facial reflexes were not brisk, and pseudobulbar affect was not present. Bell’s …