The history of paraneoplastic neurologic disorders of the CNS, PNS, and autonomic nervous systems: Perspective on the past toward a brighter future

Handbook of clinical neurology · 2026-01-01

The Impact and Utility of Genetic Panel Testing in Autoimmune Neurology Practice: A Single Center Experience (P6-8.001)

Neurology · 2025-04-07

Evaluate the impact of genetic panel testing in adult patients seen in an autoimmune neurology clinic.

Clinical Characteristics Associated With High Baseline Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels in Patients With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) From the PREVENT and CHAMPION-NMOSD Trials (S38.001)

Neurology · 2025-04-07

Evaluate associations between baseline GFAP and NfL serum levels, clinical characteristics, and time to first adjudicated on-trial relapse in PREVENT (NCT01892345) and CHAMPION-NMOSD (NCT04201262).

Consensus Recommendations for the Management of Neurosarcoidosis

Neurology Clinical Practice · 2025-01-15 · 15 citations

Background and Objectives: Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies. Methods: In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis. Expert consensus recommendations were adopted if >80% threshold of agreement was reached. Results: Of the 41 invited expert clinicians across the United States, 32 (78%) participated in the study. All round 1 respondents self-identified as neuroimmunologists (except for 1 pulmonologist). Consensus was reached regarding the need to consider neurosarcoidosis phenotype and severity to guide the choice of initial immunosuppression in both the acute (relapse) and maintenance phases. Experts endorsed the use of TNF-α inhibitors as first-line agents in selected phenotypes with poor prognosis. Neuroimaging was recommended to complement clinical surveillance for treatment response. Discussion: There was agreement on several key issues, most importantly on the need to consider neurosarcoidosis phenotype and severity when deciding initial treatment. No consensus was achieved on the dosing and duration of specific immunosuppressants, nor regarding the management of the peripheral nervous system manifestation of neurosarcoidosis. These topics warrant further investigation.

Medicare Part D Use and Costs for Immune-Mediated Neurologic Therapies

JAMA Network Open · 2025-10-20

Importance: The expansion in the number of disease-modifying therapies (DMTs) for immune-mediated neurologic diseases raises critical questions about trends in their use and cost over time and whether this growth could be contributing to escalating financial burdens within the Medicare system. Objective: To examine trends in claims and Medicare Part D payments for DMTs for immune-mediated neurologic diseases. Design and Setting: This retrospective economic evaluation analyzed Medicare Part D Prescriber Public Use Files from January 1, 2013, to December 31, 2022, restricting to prescription drug claims categorized under the clinician-defined neurology taxonomy. Only prescription drugs used as DMTs for multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic disorders were included. To ensure accuracy, these medications were validated by 2 pharmacists. The data were analyzed between October 1, 2023, and November 12, 2024. Main Outcomes and Measures: Ten-year trends in total payments, number of claims, and payment per claim for DMTs were assessed for their contribution to overall cost increases. Inflation adjustments were applied using both medical care-specific and prescription drug-specific indices. Results: Between 2013 and 2022, 63 unique drugs used as DMTs for multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic disorders (eg, autoimmune encephalitis, myasthenia gravis) accounted for 6 526 278 claims and contributed $35 billion in Medicare drug expenditures. Between 2013 and 2022, annual claims for DMTs increased by 3.8% (from 549 766 to 570 298 claims). However, total payments for DMTs saw a disproportionate increase of 70.3% (95% CI, 13.5%-130.3%) from 2013 to 2022. After adjusting for medical care or prescription drug inflation, 2022 payments per claim increased by 29.1% (95% CI, 15.6% to 51.6%) and 35.9% (95% CI, 29.5%-50.3%), respectively, indicating that the rise in drug costs exceeded adjustments for medical care or prescription drug inflation rates. For the 29 DMTs available over the entire 10-year period, total claims decreased by 14.8% (from 546 026 to 465 089). Despite this reduction in claims, total payments increased by 60.5% (95% CI, 50.9%-90.6%). After adjusting for medical care inflation, the total payment increased significantly by 26.2% (95% CI, 10.5%-49.4%). Conclusions and Relevance: Over the past decade, Medicare Part D expenditures for DMTs targeting immune-mediated neurologic diseases have increased substantially, despite relatively stable claim volumes. These findings show that increases have consistently outpaced inflation rates, adding substantial economic pressure to federally funded neurologic care.

Autoimmune encephalitis

Nature Reviews Disease Primers · 2025-09-11 · 16 citations

Autoimmune encephalitis (AE) is a treatable neuro-inflammatory disorder that is increasing in incidence. AE can be associated with malignancy (paraneoplastic), but in many patients no tumour is present. The disease presentation of AE can be heterogeneous depending on the type of antibody involved. AE is often caused by neuronal antibodies that bind to extracellular autoantigens (that is, N-methyl-D-aspartate receptor (NMDAR) and LGI1). Binding of these antibodies causes dysfunction of synaptic receptors, which leads to neurological symptoms. In these patients, treatment with immunosuppressive therapies is believed to decrease inflammation and deplete antibodies, and is essential for recovery. AE can also occur in patients with antibodies against intracellular antigens (such as Hu and Ri), often in the setting of malignancy. In these patients, tumour treatment is essential for stabilization or improvement. The most frequent symptoms of AE are cognitive problems, behavioural changes and seizures. Rapid recognition of AE syndromes is essential as earlier treatment of AE leads to better outcomes. For a definite diagnosis, the identification of an autoantibody is essential; however, some patients have seronegative AE. Most patients are severely affected during the acute disease stage, but long-term functional recovery is often good, particularly for patients without cancer. Nevertheless, residual anxiety, fatigue and cognitive problems can considerably affect quality of life. Research focuses on improving the understanding of pathophysiological processes, establishing patient-tailored outcome measures, optimizing treatment prediction models and studying different therapeutic regimens, all aiming to improve treatment and long-term outcomes.

An updated, comprehensive meta-analysis of the treatment of anti-NMDAR encephalitis: Analysis, equipoise, and the urgent need for evidence over anecdote

Journal of Neuroimmunology · 2025-05-27 · 8 citations

BACKGROUND: There are no FDA-approved treatments for anti-N-methyl-d-aspartate receptor encephalitis (NMDARE), and no prospective, multicenter clinical trials have been completed to provide evidence for management of this disease. We evaluated changes in treatment strategies and outcomes since the previous comprehensive review in 2019. METHODS: A systematic literature review was conducted in PubMed capturing manuscripts published from January 2019 through March 2024. Demographic and clinical data were extracted from articles containing individual immunotherapy data in NMDARE and were compared to a previously published literature review. Studies with ≥10 cases, ≥6 months follow-up, and outcomes reported as favorable (modified Rankin Scale [mRS] 0-2) and poor (mRS 3-5 or 3-6), were grouped and summarized by diagnosis period. RESULTS: Among 649 patients from 321 articles, first- (from 91.3 % to 98.3 %, p < 0.001) and second-line (from 31.8 % to 42.5 %, p < 0.001) immunotherapy use has increased. The proportion of patients receiving immunotherapy within 30 days of symptom onset increased from 50.1 % to 72.5 % (p < 0.001). Favorable outcome (mRS 0-2) increased from 71.5 % to 76.7 % (p = 0.024), while mortality (6.3 % to 6.9 %, p = 0.714) and relapse rates (12.6 % vs. 13.2 %, p = 0.789) remained unchanged. Data from larger cohort studies of patients diagnosed with NMDARE after 2013 have reported wide variability in the proportion of patients achieving a favorable outcome at final follow-up, ranging from 56 % to 93 %, depending on the institution and follow-up duration. CONCLUSIONS: Since 2019, more patients have been treated early with first- and second-line immunotherapies. Functional outcomes have shown modest improvements, whereas mortality and relapse rates have remained unchanged.

The Urgent Need for Evidence Over Anecdote: Equipoise in the ExTINGUISH Clinical Trial in Anti-NMDAR Encephalitis (P7-8.016)

Neurology · 2025-04-07

Assess whether treatment strategies and patient outcomes in anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) have evolved since the last comprehensive review of the literature in January 2019.

A Phase-2B Double-Blind Randomized International Prospective Trial of Inebilizumab in NMDAR Encephalitis: The ExTINGUISH Trial

Neurology Open Access · 2025-04-25 · 6 citations

Background and Objectives: plasmablasts, some plasma cells, and NMDAR autoantibodies, with the potential to improve short-term and long-term outcomes in patients with NMDAR encephalitis. Methods: The ExTINGUISH trial is a multisite, phase 2B, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of inebilizumab 300 mg for the acute treatment of participants with moderate-to-severe NMDAR encephalitis. ExTINGUISH will randomize 116 patients across the United States and Europe. Participants will receive standard first-line immunotherapies (intravenous steroids and intravenous immunoglobulins and/or plasma exchange) before randomization (1:1). In addition, cyclophosphamide rescue therapy will be offered to participants with persistent moderate-to-severe disease 6 weeks after randomization. Primary outcomes will be measured 16 weeks from randomization using the change in the adapted ExTINGUISH modified Rankin scale and accepted safety measures in 32 weeks. Secondary outcomes will be measured up to 96 weeks and include comprehensive neuropsychological tests, bedside cognitive screening tools, and quality-of-life/functional indices. Clinical data will be combined with blood and CSF biomarkers of immune activation to inform putative biologic contributors to outcomes (exploratory outcomes). Study operations are supported by the National Institute of Neurological Disorders and Stroke-supported Network for Excellence in Neuroscience Clinical Trial (NeuroNEXT) infrastructure. Discussion: The ExTINGUISH trial will determine the safety and efficacy of inebilizumab as a treatment of NMDAR encephalitis while evaluating the utility of clinical, cognitive, and quality-of-life outcome measures and supporting standardized collection and measurement of biofluid biomarkers. These innovations will inform development of future treatments and trials for patients with NMDAR encephalitis and other types of autoimmune encephalitis. The ExTINGUISH trial opened to enrollment of adult patients (older than 18 years) in 2022 and pediatric patients (older than 12 years) in 2024; enrollment is ongoing.

Shooting in the Dark? A Single-Center Experience of Neural Autoantibody Panel Testing (P9-8.009)

Neurology · 2025-04-07

Determine the frequency of positive results from neural autoantibody panels performed on patients evaluated at the University of Utah Hospitals and Clinics.