Predictors for the development of neurological immune-related adverse events of immune checkpoint inhibitors and impact on mortality.

BACKGROUND AND PURPOSE: Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort. METHODS: Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models. RESULTS: Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare. CONCLUSIONS: Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.

Pediatric anti-NMDA-receptor autoimmune encephalitis in siblings: Developmental, Electrophysiologic, and Genetic Implications.

BACKGROUND: Anti-NMDAR encephalitis is a leading cause of autoimmune encephalitis in children. Untreated disease can lead to long-term neurological disability. CASE REPORT: We present siblings with pediatric-onset anti-NMDAR encephalitis. One was treated early, while the other's diagnosis and treatment were delayed by several years. Developmental, electrophysiologic, and genetic implications are discussed. CONCLUSION: Anti-NMDAR encephalitis is a severely debilitating disease that often requires prompt initiation and early escalation in treatment. Delayed treatment may lead to irreversible neurological sequalae. Further studies exploring associations between timing and tier of treatment initiation and longitudinal outcomes are needed.

Pearls & Oy-sters: Hemorrhagic Myelitis Following SARS-CoV-2 Infection.

Hemorrhage in the setting of myelitis is rarely seen in clinical practice. We report a series of 3 women aged 26, 43, and 44 years, who presented with acute hemorrhagic myelitis within 4 weeks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two required intensive care, and 1 had severe disease with multiorgan failure. Serial MRI of the spine demonstrated T2-weighted hyperintensity with T1-weighted postcontrast enhancement in the medulla and cervical spine (patient 1) and thoracic spine (patients 2 and 3). Hemorrhage was identified on precontrast T1-weighted, susceptibility-weighted, and gradient echo sequences. Distinct from typical inflammatory or demyelinating myelitis, clinical recovery was poor in all cases, with residual quadriplegia or paraplegia, despite immunosuppression. These cases highlight that although hemorrhagic myelitis is rare, it can occur as a post/parainfectious complication of SARS-CoV-2 infection.

Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis.

BACKGROUND: Several studies have demonstrated reduced serological response to vaccines in patients treated with anti-CD20 agents. However, limited data exist surrounding the clinical effect of disease modifying therapy (DMT) use on vaccine efficacy. OBJECTIVES: To investigate breakthrough coronavirus disease 2019 (COVID-19) in vaccinated people with multiple sclerosis (PwMS) on DMT. METHODS: PwMS on DMT diagnosed with COVID-19 after full vaccination were identified from an existing Cleveland Clinic COVID-19 registry, supplemented by provider-identified cases. Demographics, disease history, DMTs, comorbidities, exposures, vaccination status, and COVID-19 outcomes were confirmed by review of the electronic medical record. RESULTS: Thirteen (3.8%) of 344 fully vaccinated people with multiple sclerosis on disease modifying therapy were diagnosed with COVID-19 after vaccination. Ten patients (76.9%) were on an anti-CD20 therapy, the remaining 3 (23.1%) on fingolimod. Only 2 patients (15.4%), both on anti-CD20 therapy, required hospitalization and steroid treatment. Neither required Intensive Care Unit admission. CONCLUSION: Patients treated with anti-CD20 agents and sphingosine 1-phosphate receptor modulators may still be at risk for COVID-19 despite vaccination. While still at risk for hospitalization, intubation and death from COVID-19 appear rare. Larger studies analyzing how this may differ in the setting of emerging variants are needed.

Fertility counseling and sperm banking among adolescents and adults treated for cancer with curative intent in a developing country.

PURPOSE: In developing countries, a higher percentage of patients develop cancer at a younger age. Cancer survival rates have significantly improved, highlighting the importance of survivorship programs that address late complications related to cancer itself or its treatment. The purpose of this study is to estimate the prevalence of fertility counseling and sperm banking and related factors among at-risk males newly diagnosed with cancer and planning to receive a potentially curative anticancer therapy. METHODS: Medical records and hospital database of young male patients with newly diagnosed cancers and planned to start chemotherapy were reviewed for fertility counseling and sperm cryopreservation. Additionally, a self-administered questionnaire was utilized. RESULTS: A total of 186 patients, mean age 32.9 (range: 18-53) years, were included. Non-Hodgkin's lymphoma 59 (31.7%), leukemia 48 (25.8%), and Hodgkin's lymphoma 26 (14.0%) were the most common tumors encountered. A total of 129 (75.0%) respondents received fertility counseling prior to their treatment, and this rate was higher among patients with early-stage disease (82.4% vs. 58.1%, p = 0.038). However, sperm banking was performed by 33.1% of the whole study group but was significantly higher among single patients (53.4% vs. 17.7%, p < 0.001), those who had no children (51.8% vs. 14.3%, p < 0.001), and among highly educated patients (47.6% vs. 17.1%, p = 0.001). Patients failed to do sperm banking because they were not informed about the risk of infertility (26.2%) or service availability (25.4%). Fear of treatment delay was a reason in 20.0%. CONCLUSIONS: Fertility counseling and sperm banking among cancer patients are not optimal. Many patients failed to do sperm banking because of avoidable reasons. Better communication and patients' education will probably improve the utilization of this vital service.

Anti-N-methyl-D-aspartate Encephalitis Concomitantly with Tall-cell Variant Papillary Thyroid Carcinoma.

Anti-N-methyl-D-aspartate (NMDA) encephalitis is an autoimmune-mediated process characterized by psychosis, seizures, dyskinetic movements, and autonomic instability. At least half of the reported cases are paraneoplastic, particularly associated with an ovarian teratoma. None have been reported to be associated with thyroid tumor. We present a case of anti-NMDA encephalitis concomitantly occurring in setting of papillary thyroid carcinoma in a woman who presented with headaches, myalgia and somnolence mimicking meningoencephalitis. A 29-year-old African female presented with fever, headache, myalgia, somnolence and behavioral changes. Initial evaluation was significant for lymphocytic pleocytosis with normal glucose and protein. She was started on broad spectrum empiric antibiotics. Despite antibiotics, she continued to have worsening encephalopathy, hallucinations, epileptic seizures, and multifocal dyskinesias involving the face and extremities with no electroencephalogram correlate. Extensive infectious workup was unremarkable. Whole-body CT with contrast and ovarian ultrasound were unremarkable for malignancy. Serum auto-antibodies to the NMDA receptor and thyroid peroxidase were detected. She was treated with high-dose intravenous steroids, plasmapheresis, intravenous immunoglobulin, and rituximab with no clinical or serological response. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed a hypermetabolic thyroid nodule. Fine needle aspiration of the nodule revealed papillary thyroid carcinoma. She underwent total thyroidectomy and pathology showed two foci of tall-cell variant papillary thyroid carcinoma. Serological and clinical response followed shortly after tumor resection. The NMDA receptor stain of the papillary thyroid carcinoma was nonreactive. We describe the coincidentally co-occurrence of NMDA encephalitis in a patient with papillary thyroid carcinoma. This case highlights the importance of presumed cases of non-paraneoplastic NMDA encephalitis, FDG-PET may help in detecting occult malignancies.