Mogamulizumab-Associated Myositis With and Without Myasthenia Gravis and/or Myocarditis in Patients With T-Cell Lymphoma.

Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular immune-related adverse events (irAEs) associated with mogamulizumab in patients with T-cell lymphoma followed at Dana-Farber Cancer Institute from January 2015 to June 2022. We identified 5 cases of mogamulizumab-associated myositis and/or myocarditis (MAM/Mc), 2 additionally affected by myasthenia gravis, among 42 patients with T-cell lymphoma. Three cases experienced -mogamulizumab-associated rash (MAR) prior to developing MAM/Mc. The incidence (n = 5/42, 11.9%) of muscular mogamulizumab-associated irAEs may be higher than has been previously reported in clinical trials and may be of late onset (a median of 5 cycles and as late as 100 days from the last infusion). We highlight the utility of IVIG, together with systemic corticosteroids, for the treatment of these potentially fatal side effects associated with mogamulizumab therapy.

Guillain-Barré Syndrome Presenting as Facial Diplegia after COVID-19 Vaccination: A Case Report.

BACKGROUND: Guillain-Barré Syndrome (GBS) is a rapidly progressive immune-mediated polyneuropathy often associated with an antecedent infectious illness or vaccination. The classic presentation of GBS is characterized by ascending limb weakness and numbness with loss of reflexes. However, atypical variants involving the face and arms or with purely sensory symptoms also exist. In up to 30% of cases, GBS progresses to respiratory failure, with patients requiring mechanical ventilation. CASE REPORT: We report a case of atypical GBS occurring after Coronavirus disease 2019 (COVID-19) vaccination in an otherwise healthy 38-year-old man. The patient's clinical presentation was characterized by bilateral hand and foot paresthesias, dysarthria, bilateral facial weakness, and an absence of classic ascending limb weakness. Albuminocytological dissociation within the cerebrospinal fluid was suggestive of GBS. The patient received intravenous immunoglobulin therapy, with modest improvement in his symptoms at the time of his discharge from the hospital. Why Should an Emergency PhysicianBe Aware of This? Patients with GBS are at risk for life-threatening complications, including respiratory failure requiring mechanical ventilation. It is critical for emergency physicians to be aware of the manifold presentations of GBS for early recognition and treatment. This may be of particular importance in the context of a worldwide vaccination campaign in response to the COVID-19 pandemic.

Fibrosing Inflammatory Pseudotumor Presenting as Cranial Neuropathy.

We report two cases of biopsy-corroborated "fibrosing inflammatory pseudotumor" to illustrate that the entity, rarely described in the neurological literature, should be included in the differential diagnosis of either a cranial mononeuropathy or, certainly, in the case of progressive cranial neuropathies. A broad differential diagnosis arises in certain contexts. Early steroid treatment can be effective, and perhaps later-generation immune-modulating agents may confer further options, although there is no known definitive treatment.

Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration?

We describe a man whose first manifestations of Creutzfeldt-Jakob disease occurred in tandem with symptomatic onset of coronavirus disease 2019 (COVID-19). Drawing from recent data on prion disease pathogenesis and immune responses to SARS-CoV-2, we hypothesize that the cascade of systemic inflammatory mediators in response to the virus accelerated the pathogenesis of our patient's prion disease. This hypothesis introduces the potential relationship between immune responses to the novel coronavirus and the hastening of preclinical or manifest neurodegenerative disorders. The global prevalence of both COVID-19 and neurodegenerative disorders adds urgency to the study of this potential relationship.

Update on Ocular Myasthenia Gravis.

Myasthenia gravis is an antibody-mediated autoimmune disorder of the post-synaptic neuromuscular junction resulting in fluctuating, fatigable weakness. Most patients first present with extraocular symptoms (diplopia and/or ptosis), and in 15% of cases symptoms will remain restricted to only the extraocular muscles (ocular myasthenia gravis [OMG]). The history and clinical examination are of the utmost importance in correctly identifying OMG patients, as supportive serologic or electrodiagnostic studies are frequently nondiagnostic. In this review, we outline a diagnostic approach to OMG (focusing on key clinical features), discuss therapeutic options, and highlight recent developments in the understanding of OMG.

A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis.

Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAEs are poorly understood. Here, we report a fatal case of encephalitis arising during anti-programmed cell death receptor 1 therapy in a patient with metastatic melanoma. Histologic analyses revealed robust T cell infiltration and prominent programmed death ligand 1 expression. We identified 209 reported cases in global pharmacovigilance databases (across multiple cancer types) of encephalitis associated with checkpoint inhibitor regimens, with a 19% fatality rate. We performed further analyses from the index case and two additional cases to shed light on this recurrent and fulminant irAE. Spatial and multi-omic analyses pinpointed activated memory CD4+ T cells as highly enriched in the inflamed, affected region. We identified a highly oligoclonal T cell receptor repertoire, which we localized to activated memory cytotoxic (CD45RO+GZMB+Ki67+) CD4 cells. We also identified Epstein-Barr virus-specific T cell receptors and EBV+ lymphocytes in the affected region, which we speculate contributed to neural inflammation in the index case. Collectively, the three cases studied here identify CD4+ and CD8+ T cells as culprits of checkpoint inhibitor-associated immune encephalitis.

Journal Club: Exacerbation of headache during dihydroergotamine for chronic migraine does not alter outcome.

Transient headache exacerbation during IV dihydroergotamine (DHE) therapy of migraine may prompt clinicians to prematurely discontinue DHE therapy, potentially depriving patients of the full benefit of DHE infusion. In a recent Neurology® article, Eller et al. evaluated whether or not worsening headache during DHE infusion was associated with suboptimal medium-term headache outcomes.

Cardio-oncology Part I: chemotherapy and cardiovascular toxicity.

Cancer and cardiovascular disease are the most common causes of mortality in the US, causing approximately 1.2 million deaths annually. The incidence of cancer is expected to increase as the population ages. The prognosis of cancer patients has improved over the last few decades primarily because of newer chemotherapeutic drugs; however, many of these drugs have cardiotoxic side effects. The short-term cardiovascular toxicities of more established drugs are well described; however, understanding of the underlying pathogenesis is increasing. The delayed cardiotoxic effects of cancer treatments have become an important issue contributing to mortality and morbidity as cancer survivorship increases. Chemotherapy-induced cardiotoxicity can manifest in many ways, from asymptomatic decreases in left ventricular ejection fraction to congestive heart failure. Hypertension is commonly seen both as a co-morbidity and a side effect of chemotherapy. In this article, we discuss the pathogenesis, scope, presentation and potential prevention of these toxicities.

Cardio-oncology Part II: the monitoring, prevention, detection and treatment of chemotherapeutic cardiac toxicity.

Cancer treatment has advanced in recent years with new drugs, complex regimes and multiple modalities of treatment; which has improved survival of cancer patients. Cardiotoxicity from chemotherapy is an emerging, important issue. Currently, echocardiographic evaluation of ejection fraction is the most commonly employed diagnostic tool for detecting chemotherapy-induced cardiotoxicity. However, novel echocardiographic techniques assessing myocardial mechanics using strain imaging can detect earlier changes. New imaging techniques and biomarkers can risk stratify patients to identify those requiring closer monitoring. Cardiologists collaborating with oncologists can detect and treat cardiovascular chemotherapeutic complications earlier, reducing morbidity and mortality. While cardiac MRI and multigated acquisition nuclear scanning are alternatives, echocardiography has become the mainstream for assessing cardiac function due to its portability, efficiency and low cost. Current recommendations regarding cardiac monitoring of cancer patients are based on expert consensus opinion. There is a need for prospective controlled trials to support specific guidelines.