Divyanshu Dubey

Smart Phone Applications as a Source of Information on Stroke

Background and Purpose Smartphone applications have been increasingly identified as a novel platform for dissemination of healthcare related information. However, there have been no studies done to evaluate the availability and content of stroke related apps. Purpose: This study aims to identify and analyze stroke-related applications available on the Apple iTunes and Android Google Play Store. Methods The Apple iTunes store and Android Google Play Store were searched for stroke-related applications on July 27, 2013 using keywords: stroke, brain attack, intracranial hemorrhage, subarachnoid hemorrhage, cerebral infarction. The content of the applications was analyzed by two independent investigators. Results A total of 93 relevant applications (46.2% android and 53.8% iPhone) were identified of which 47.3% were available free of cost. 92% of apps were identified as useful by users and over 60% had scientifically valid information. There is a significant participation of healthcare agencies in dissemination of stroke related information through apps with 47.3% apps being uploaded by them. Over half of all stroke related apps were aimed towards health care workers (51.6%), 75% of which could be utilized as bedside tools for patient care and remainder had information related to recent research advances. The difference in scientific validity between the apps aimed at general population versus healthcare professionals was statistically significant (P<0.01). There was no statistical association between cost of app and scientific validity or usefulness. Conclusions Smartphone apps are a significant source of information related to stroke. An increasing participation of healthcare agencies should be encouraged to promote dissemination of scientifically valid information.

Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology

Importance Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients’ condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. Objective To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Design, Setting, and Participants Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016. Main Outcomes and Measures Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom. Results Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an autoimmune cause of epilepsy were seen in 23 patients (20.5%). Certain clinical features, such as autonomic dysfunction, neuropsychiatric changes, viral prodrome, faciobrachial dystonic spells or facial dyskinesias, and mesial temporal sclerosis abnormality on magnetic resonance imaging, correlated with seropositivity. The APE score was a useful tool in predicting positive serologic findings. Patients who were Ab positive were more likely to have good seizure outcome than were patients with epilepsy of unknown etiology (15 of 23 [65.2%] vs 24 of 89 [27.0%]; odds ratio, 4.8; 95% CI, 1.8-12.9; P = .002). In patients who were seropositive, reduction in seizure frequency was associated with use of immunomodulatory therapy. Conclusions and Relevance Among adult patients with epilepsy of unknown etiology, a significant minority had detectable serum Abs suggesting an autoimmune etiology. Certain clinical features (encoded in the APE score) could be used to identify patients with the highest probability of harboring neurological Abs.

Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG–positive patients

To describe an expanded phenotypic spectrum and longitudinal outcome in 256 LGI1‐IgG–seropositive and/or CASPR2‐IgG–seropositive patients.

Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis

To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.

The spectrum of autoimmune encephalopathies

Despite being a potentially reversible neurological condition, no clear guidelines for diagnosis or management of autoimmune encephalitis exist. In this study we analyzed clinical presentation, laboratory and imaging characteristics, and outcome of autoimmune encephalitis from three teaching hospitals. Non-paraneoplastic autoimmune encephalitis associated with antibodies against membrane antigens was the most common syndrome, especially in the pediatric population. Clinical outcome was better for patients with shorter latency from symptom onset to diagnosis and initiation of immunomodulation. Patients with underlying malignancy were less likely to respond well to immunomodulatory therapy. The clinical spectrum of autoimmune encephalitis is fairly broad, but prompt recognition and treatment often leads to excellent outcome.

Retrospective case series of the clinical features, management and outcomes of patients with autoimmune epilepsy

PURPOSE Analyze clinical and electrographic characteristics of patients with autoimmune epilepsy, and evaluate the effect of early diagnosis and treatment on reduction of seizure frequency. METHODS Observational retrospective case series, conducted using electronic medical data from two teaching hospitals. Clinical data was collected from 2008 to 2013. Cases of new onset seizures were selected based on the presence of laboratory evidence of autoimmunity. RESULTS 34 hospitalized patients who presented predominantly due to seizures with concern for autoimmune etiology were identified. Mean age of patients was 44.94 years and 64.7% were males. Autoimmune antibodies were detected in 76.5% (26) of patients as follows: VGKc (8); NMDA-R (7); anti-thyroid (5); GAD (4); GABAB (2). 22 patients had unilateral temporal lobe onset and 4 had bilateral temporal lobe onset, while 8 had extra-temporal onset/multiple ictal foci. Median number of seizures during initial prolonged vEEG monitoring was 8 (range 0-48); median number of anti-seizure medications used was 2 (range 1-5). 9 patients had an underlying malignancy. 94.1% (32) patients received immunomodulation, as follows: high dose corticosteroids (96.8%), plasmapheresis (62.5%), IVIG (34.4%), rituximab (21.8%), mycophenolate (15.6%), cyclophosphamide (12.5%). 63.3% (19) participants achieved ≥ 50% seizure reduction (Responder Rate) at first clinic visit. Patients without malignancy had better seizure control (p < 0.05). Time from symptom onset to diagnosis (p < 0.005) and symptom onset to immunomodulation (p < 0.005) was significantly lower among patients who achieved responder rate (RR). CONCLUSION This study highlights certain important clinical and electrographic aspects of autoimmune epilepsy, and the significance of early diagnosis and initiation of immunomodulatory therapy.

Clinical management of multiple sclerosis and neuromyelitis optica with therapeutic monoclonal antibodies: approved therapies and emerging candidates

Therapeutic monoclonal antibodies (mAbs) are a relatively novel class of drugs that has substantially advanced immunotherapy for patients with multiple sclerosis. The advantage of these agents is that they bind specifically and exclusively to predetermined proteins or cells. Natalizumab was the first mAb in neurology to obtain approval. It is also considered one of the most potent options for annualized relapse rate reduction among available therapeutic options. Alemtuzumab is currently also approved in several countries. Several mAbs have been tested in clinical studies in multiple sclerosis. Here, we review the history of drug development of therapeutic mAbs and their classification. Furthermore, we outline the putative mechanisms of action, clinical evidence and safety of approved mAbs and those in different stages of clinical development in multiple sclerosis and neuromyelitis optica.

Effectiveness of multimodality treatment for autoimmune limbic epilepsy.

We evaluated the outcome of multimodality treatment in autoimmune limbic epilepsy in 3 consecutive patients (2 male and 1 female; age 33-55 years) presenting with a combination of focal non-convulsive status epilepticus, memory impairment, and psychosis. MRI showed right or bitemporal T2 or FLAIR hyperintensity. Video-EEG showed seizures of right temporo-occipital or bitemporal independent onset. Extensive workup failed to reveal infectious aetiology or an underlying tumour. However, the autoantibody panel was positive for one or more of these antibodies: anti-VGKC, anti-GABAB, anti-VGCC (P/Q, N types), and anti-GAD65. All patients received: (1) conventional antiepileptic drugs including levetiracetam, lacosamide, phenobarbital, lamotrigine, and valproate; (2) immunomodulatory therapy including methylprednisolone, plasmapheresis, and intravenous immunoglobulin; and (3) rituximab. After a 4-6-week in-hospital course, the seizures resolved in all patients but 2 had persistent memory impairment. None had treatment-related complications. At the time of last follow-up, 2-3 months later, 2 patients remained seizure-free while 2 had residual memory impairment. Our findings suggest that multimodality treatment with a combination of conventional AEDs, immunomodulatory therapy, and rituximab is effective and safe in autoimmune limbic epilepsy.

GAD65 Positive Autoimmune Limbic Encephalitis: A Case Report and Review of Literature

Limbic encephalitis is a rare disorder affecting the medial temporal lobe of the brain, sometimes also involving hippocampus atrophy. It was initially considered to be only of paraneoplastic origin but now auto-immune (non-paraneoplastic) cases have also been reported. Most common non paraneoplastic antibodies associated with limbic encephalitis are Voltage gated potassium channel antibodies, NMDA receptor antibodies and GAD receptor antibodies. We present a case of limbic encephalitis which presented with sudden onset seizures which was preceded by confusion, disorientation and other psychiatric symptoms for a period of 5 weeks. No tumor was found on imaging and the classic paraneoplastic panel was negative. CSF and serum examination showed high titers GAD65 antibody guiding towards a diagnosis of non paraneoplastic limbic encephalitis. Her symptoms and GAD 65 antibody titers showed significant improvement following immunomodulatory therapy. The case presented here is unique and scientifically relevant, as it intends to raise awareness of Auto-immune Limbic Encephalitis, a potentially reversible cause of a medical emergency.

Predictive models in the diagnosis and treatment of autoimmune epilepsy

To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy.