Peripheral nervous system manifestations of MOG antibody associated disease.

Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG-IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true-positive MOG-IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

Use of Point-of-Care Ultrasound by Intensive Care Unit Triage Teams in Evaluating Unstable Patients Outside Intensive Care Units.

Introduction Point-of-care ultrasound (POCUS) has become an integral asset in intensive care units (ICUs). However, there is limited literature on the value of POCUS in evaluating deteriorating patients outside the ICU. In this study, we sought to investigate the use and impact of POCUS by ICU triage teams in hospitals outside of the ICU setting. Methods ICU triage fellows were provided a portable ultrasound to use as part of their evaluations during consultations and hospital code activations. Fellows were asked to fill out a survey on how ultrasound was used and its impact on patient management. Free-text data such as reason for ultrasound use, views obtained, clinical impressions before and after ultrasound, and clinical actions were recorded. These data were transcribed and categorized electronically. Results A total of 51 total resuscitations were documented. The most common reason for ICU triage team evaluation was hypotension (53%, N=27). The most common clinical focus for ultrasound use was cardiac assessment (53%, N=27), followed by volume status assessment (35%, N=18). The most common ultrasound views per encounter obtained were parasternal long (82%, N=42), followed by apical four-chamber view (76%, N=39) and subcostal view (75%, N=38). Out of 38 encounters with clinical impressions documented, 79% (N=30) of pre-ultrasound clinical impressions were confirmed by ultrasound use. Of total encounters, 35% (N=18) had a significant clinical action taken based on ultrasound findings (fluid resuscitation, vasopressor initiation, etc.). Conclusions Ultrasound is a valuable tool for patient evaluation in non-ICU wards, especially in confirming clinical impressions and guiding therapeutic actions. Some limitations of this study include reporting bias and incomplete capture of ultrasound use in non-ICU wards.

Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome.

Introduction: The development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples. Methods: Stored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization. Results: PhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2-specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative. Discussion: SKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.

Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies.

OBJECTIVE: Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures. METHODS: Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated. RESULTS: Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p = .04), highest seizure frequency being at least daily (p = .0002), seizures on electroencephalogram (EEG; p = .03), and imaging evidence of limbic encephalitis (LE; p = .03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p = .04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures. SIGNIFICANCE: Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.

A comparative analysis of demographic, clinical and imaging features of myelin oligodendrocyte glycoprotein antibody positive, aquaporin 4 antibody positive, and double seronegative demyelinating disorders - An Indian tertiary care center prospective study.

Objectives: The aim of the study was to study the demographical, clinical, radiological features, and outcome of anti-myelin oligodendrocyte glycoprotein (MOG) antibody spectrum disorder and compare these features with patients negative for anti-MOG antibody. MOG antibody-associated disease (MOGAD) and aquaporin-4 (AQP4) antibody-related diseases are immunologically distinct pathologies. Our aim was to compare the clinical and radiological features of MOG antibody-related diseases with AQP4 antibody-related diseases and seronegative demyelinating diseases (Non-multiple sclerosis). Materials and Methods: This was a prospective and cohort study conducted at an apex tertiary care institute in the northern part of India from Jan 2019 to May 2021. We compared clinical, laboratory, and radiological findings of patients with MOGAD, AQP4 antibody-related diseases, and seronegative demyelinating disease. Results: There were a total of 103 patients - 41 patients of MOGAD, 37 patients of AQP4 antibody-related diseases and 25 seronegative demyelinating disease. Bilateral optic neuritis was the most frequent phenotype in patients with MOGAD (18/41) whereas myelitis was the most common phenotype in the AQP4 (30/37) and seronegative groups (13/25). Cortical, juxtacortical lesions, anterior segment optic neuritis, optic sheath enhancement, and conus involvement in myelitis were radiological findings that separated MOGAD from AQP4 related diseases. Nadir Expanded Disability Status Scale (EDSS) and visual acuity were similar across the groups. Last follow-up EDSS was significantly better in the MOG antibody group as compared to AQP4 antibody group (1 [0-8] vs. 3.5 [0-8]; P = 0.03). Encephalitis, myelitis, and seizures were more common in the younger population (<18 vs. >18 years) in MOGAD (9 vs. 2, P = 0.001; 9 vs. 7, P = 0.03; 6 vs. 0, P = 0.001). Conclusion: We identified several clinical and radiological features that can help physicians to distinguish MOGAD from AQP4-immunoglobulin G+neuromyelitis optica spectrum disorder. Differentiation is vital as treatment response might vary among both groups.

Growing Spectrum of Autoimmune Nodopathies.

PURPOSE OF REVIEW: Recognition of node of Ranvier as the site of injury in inflammatory neuropathies contributed to discovery of antibodies against the nodal/paranodal structures. These antibodies mediate a unique type of inflammatory neuropathies that are different from typical chronic inflammatory demyelinating polyneuropathy. This review discusses the advancements made in the field of autoimmune neuropathies secondary to antibodies to nodal and paranodal proteins. RECENT FINDINGS: Neuropathies caused by antibodies to nodal-paranodal antigens including neurofascin 186, neurofascin 155, contactin1, and contactin-associated protein1 were termed as autoimmune nodopathies (AN) in 2021. Since the initial description almost a decade ago, newer cohorts have expanded the clinical spectrum of AN. In addition to IgG4, other subclasses of IgG such as IgG1/IgG3 have been identified, particularly in relation to acute presentations and anti-pan neurofascin antibody disease. In vitro and in vivo studies have also supported antibody-mediated pathogenicity of many of these biomarkers. Antibodies to nodal-paranodal antigens have emerged as a biomarker for a novel type of immune-mediated neuropathies. These antibodies have distinct pathogenic mechanisms and produce a unique set of clinicopathologic features. Their clinical profile and treatment may also vary depending on the antibody isotype. B cell depleting therapies are effective in managing some of these patients.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

Anatomical Variation in Quadriceps Angle With Regard to Different Anthropometric Parameters in a Tertiary Care Center in Northern India: A Descriptive Study.

BACKGROUND: The quadriceps angle, commonly known as the Q-angle, is the angle formed between the vectors of the pull of the quadriceps muscle and the patellar tendon. The literature varies in terms of the values of Q angles measured by various researchers. It is well appreciated that the normal Q-angle should fall between 12° and 20°, with males being at the lower end of this range and females having higher measurements. An increase in Q-angle beyond the normal range has been associated with knee extensor dysfunction leading to patellar instability. Keeping in mind the clinical and biomechanical importance of the Q-angle, the aim of this study was to compare and establish the range of the Q-angle in healthy individuals and evaluate its variations with respect to age, weight, height, gender, dominant side, and femoral bicondylar distance. These observations will be helpful for sports therapists in understanding the evaluation of Q-angle in athletes as a prognostic value for probable knee pathologies that may appear in the future. METHODS: The current study was conducted at a tertiary care center, and a total of 100 healthy adults between the ages of 18 and 35 were enrolled in the study (50 males and 50 females), following which their Q-angles, bicondylar distances, and femur lengths were measured. Individuals with any lower limb injury that resulted in a ligamentous, muscular, or bony defect; any spinal or neurological injury; any diagnosed knee disorder, such as a fracture, acute or chronic knee pain, patellar dislocation, or prior orthopaedic surgery in the lower extremities, were excluded from the study. Data were analyzed using paired t-tests, independent sample t-tests, ANOVA, and Pearson correlation coefficients. RESULT AND CONCLUSION: The mean Q-angle in males was found to be 11.14° ± 1.9° on the right side and 10.84° ± 1.86° on the left side. In females, it was found to be 13.68° ± 1.87° on the right side and 13.61° ± 2.04° on the left side. Among males, right and left Q-angles showed significant positive correlations with height, weight, BMI, right femur length, left femur length, right bicondylar distance, and left bicondylar distance (p<0.05). The highest correlation was found between weight and BMI. Among females, the right Q-angle showed significant positive correlations with weight and BMI (p<0.05). The highest correlation was found with weight.

Rapid Response EEG: Current State and Future Directions.

PURPOSE OF REVIEW: To critically appraise the literature on the application, methods, and advances in emergency electroencephalography (EEG). RECENT FINDINGS: The development of rapid EEG (rEEG) technologies and other reduced montage approaches, along with advances in machine learning over the past decade, has increased the rate and access to EEG acquisition. These achievements have made EEG in the emergency setting a practical diagnostic technique for detecting seizures, suspected nonconvulsive status epilepticus (NCSE), altered mental status, stroke, and in the setting of sedation. Growing evidence supports using EEG to expedite medical decision-making in the setting of suspected acute neurological injury. This review covers approaches to acquiring EEG in the emergency setting in the adult and pediatric populations. We also cover the clinical impact of this data, the time associated with emergency EEG, and the costs of acquiring EEG in these settings. Finally, we discuss the advances in artificial intelligence for rapid electrophysiological interpretation.

Comparison of Disease Profiles and Three-Month Outcomes of Patients with Neurological Disorders with and without COVID-19: An Ambispective Cohort Study.

Objective: Neurological emergencies saw a paradigm shift in approach during the coronavirus disease-2019 (COVID-19) pandemic with the challenge to manage patients with and without COVID-19. We aimed to compare the various neurological disorders and 3 months outcome in patients with and without SARS-CoV-2 infection. Methods: In an ambispective cohort study design, we enrolled patients with and without SARS CoV-2 infection coming to a medical emergency with neurological disorders between April 2020 and September 2020. Demographic, clinical, biochemical, and treatment details of these patients were collected and compared. Their outcomes, both in-hospital and at 3 months were assessed by the modified Rankin Scale (mRS). Results: Two thirty-five patients (235) were enrolled from emergency services with neurological disorders. Of them, 81 (34.5%) were COVID-19 positive. The mean (SD) age was 49.5 (17.3) years, and the majority of the patients were male (63.0%). The commonest neurological diagnosis was acute ischemic stroke (AIS) (43.0%). The in-hospital mortality was higher in the patients who were COVID-19 positive (COVID-19 positive: 29 (35.8%) versus COVID-19 negative: 12 (7.8%), P value: <0.001). The 3 months telephonic follow-up could be completed in 73.2% of the patients (142/194). Four (12.1%) deaths occurred on follow-up in the COVID-19 positive versus fifteen (13.8%) in the COVID-19 negative patients (P value: 1.00). The 3-month mRS was worse in the COVID-19 positive group (P value <0.001). However, this was driven by higher in-hospital morbidity and mortality in COVID-19 positive patients. Conclusion: Patients with neurological disorders presenting with COVID-19 infection had worse outcomes, including in-hospital and 3 months disability.

Patients with Neurological Illnesses and Their Experience During the Lockdown: A Teleinterview-based Study.

Background: Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. Materials and Methods: An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. Results: A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. Conclusion: The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses.

Bubblewrap: Online tiling and real-time flow prediction on neural manifolds.

While most classic studies of function in experimental neuroscience have focused on the coding properties of individual neurons, recent developments in recording technologies have resulted in an increasing emphasis on the dynamics of neural populations. This has given rise to a wide variety of models for analyzing population activity in relation to experimental variables, but direct testing of many neural population hypotheses requires intervening in the system based on current neural state, necessitating models capable of inferring neural state online. Existing approaches, primarily based on dynamical systems, require strong parametric assumptions that are easily violated in the noise-dominated regime and do not scale well to the thousands of data channels in modern experiments. To address this problem, we propose a method that combines fast, stable dimensionality reduction with a soft tiling of the resulting neural manifold, allowing dynamics to be approximated as a probability flow between tiles. This method can be fit efficiently using online expectation maximization, scales to tens of thousands of tiles, and outperforms existing methods when dynamics are noise-dominated or feature multi-modal transition probabilities. The resulting model can be trained at kiloHertz data rates, produces accurate approximations of neural dynamics within minutes, and generates predictions on submillisecond time scales. It retains predictive performance throughout many time steps into the future and is fast enough to serve as a component of closed-loop causal experiments.

The Distinguished Teaching Society at the Johns Hopkins University School of Medicine: A Student-Led Initiative to Recognize Clinical Educators.

PROBLEM: Some focus on recognizing excellence in clinical teaching has been lost with the increasing emphasis placed on clinical efficiency and value. Clinical teaching awards and academies of educators aim to address this problem. In 2015, medical student leaders at the Johns Hopkins University School of Medicine created the Distinguished Teaching Society (DTS), a student-driven program to recognize the best clinical educators. APPROACH: Medical students designed a comprehensive scoring rubric focusing on 3 domains: feedback and evaluation, role model behavior, and teaching process. A student committee solicits student nominations providing narratives endorsing faculty or house staff for potential inclusion in the DTS. Using the rubric, student judges score each deidentified narrative nomination, as well as an application from finalists and comments about finalists submitted by the student body. Inductees are recognized at an annual ceremony. OUTCOMES: From academic years 2015-2016 to 2018-2019, students nominated 254 unique candidates, and 82 nominees (32%) were inducted into the DTS. The majority of inductees were faculty and male. In 2017-2018 and 2018-2019, nearly half of inductees were female, and less than 10% of inductees self-reported as underrepresented in medicine and/or LGBTQ+. The Department of Internal Medicine had the greatest departmental representation. There were no statistically significant differences in the proportional representation within the nomination and inductee cohorts by gender, rank, and department. Several process changes were made in response to student feedback and to increase nominee and inductee diversity. NEXT STEPS: Next steps include adding a diversity and inclusion chair to the student committee and collecting survey data on student and DTS inductee opinions on how to improve learner-teacher engagement and the clinical learning environment. Future activities may include educational workshops, panel discussions, mentorship programs, and networking events. Other medical schools may find value in considering similar structures.

Anti-myelin oligodendrocyte glycoprotein antibody associated disease spectrum - A north Indian tertiary care centre experience and review of literature.

INTRODUCTION: MOG antibody associated disease is a relatively new disorder for which the full clinical spectrum is being described and the literature is evolving. The current study outlines the observations on a cohort of patients diagnosed with this clinical entity. METHODS: This is a retrospective review of prospectively followed up patients with MOG antibody positive neurological illness. Case records of patients following up in neuroimmunology clinic of All India Institute of Medical Sciences(AIIMS), New Delhi from January 2007 to July 2019 were reviewed for MOG antibody positivity and those patients with positive antibody result were included in this study. FINDINGS: A total of 20 patients were tested positive for MOG-IgG antibody. 75% were females. Median (Range) age was 30.5 years (8-58). Median disease duration was 22 months (1-139). Most common symptom at presentation was decrease in vision (unilateral or bilateral) (80%). Most common syndrome at onset was unilateral optic neuritis (ON) (40%) followed by bilateral ON (35%), transverse myelitis (TM)(15%), ON plus TM (5%) and cerebral syndrome (5%). Median number of demyelinating episodes per person was 2.5. Out of 29 affected eyes, 26 had good outcome. Out of 7 patients with motor disability, 5 patients had good outcome. CONCLUSION: MOG antibody associated disease presents predominantly as recurrent ON, but may also present as an opticospinal, cerebral or brainstem syndrome and recurrent myelitis. Many of the patients had relapses, but had good outcomes with treatment.

Functional characterization of retinal ganglion cells using tailored nonlinear modeling.

The mammalian retina encodes the visual world in action potentials generated by 20-50 functionally and anatomically-distinct types of retinal ganglion cell (RGC). Individual RGC types receive synaptic input from distinct presynaptic circuits; therefore, their responsiveness to specific features in the visual scene arises from the information encoded in synaptic input and shaped by postsynaptic signal integration and spike generation. Unfortunately, there is a dearth of tools for characterizing the computations reflected in RGC spike output. Therefore, we developed a statistical model, the separable Nonlinear Input Model, to characterize the excitatory and suppressive components of RGC receptive fields. We recorded RGC responses to a correlated noise ("cloud") stimulus in an in vitro preparation of mouse retina and found that our model accurately predicted RGC responses at high spatiotemporal resolution. It identified multiple receptive fields reflecting the main excitatory and suppressive components of the response of each neuron. Significantly, our model accurately identified ON-OFF cells and distinguished their distinct ON and OFF receptive fields, and it demonstrated a diversity of suppressive receptive fields in the RGC population. In total, our method offers a rich description of RGC computation and sets a foundation for relating it to retinal circuitry.