Myasthenia gravis is an antibody-mediated autoimmune condition characterized by defects in cholinergic transmission at the neuromuscular junction. In AchR antibody-positive patients, complement activation plays a prominent role in the disease process, which appears to be mediated by the activation of the membrane attack complex. Since IgG4 is not a good complement activator, the role of complement in MuSK antibody-positive myasthenia gravis patients is negligible. Experimental animal models of myasthenia gravis have shown promise with the antagonism of different elements of the complement cascade, with positive clinical outcomes. This has led to the development of the first C5 inhibitors approved for myasthenia gravis with AchR antibodies: eculizumab, ravulizumab, and zilucoplan. Other clinical trials are currently in progress, investigating the potential therapeutic role of other targets, including the Factor B inhibition or hepatic synthesis of the C5 protein. Other proposed potential targets that have not yet been clinically tested are also discussed in this review article.

The use of immune checkpoint inhibitors (iCPI) in the treatment of multiple cancers has gained prominence due to their high efficacy. However, neurological immune-related adverse events (irAEs) such as myasthenia gravis (MG) have been associated with iCPI therapy. Most of these neurological irAEs are rare, and in many cases, their diagnoses and management can be challenging. We present a case of a 70-year-old woman with stage IIIC melanoma who developed a new onset of gradually progressive dyspnea, diplopia, and bilateral ptosis following treatment with one cycle of nivolumab and ipilimumab (Nivo+Ipi). She was diagnosed with MG via positive serum acetylcholine receptor (AChR) antibodies. She had developed a severe dyspnea at rest, which was refractory to multiple immune-suppressive therapies including prednisone, pyridostigmine, and intravenous immunoglobulin (IVIG). Subsequently, she was treated with rituximab 375 mg/m² monthly every four weeks with significant improvement of her symptoms within 48 hours each time. As the implementation of immunotherapy increases in medical practice, irAEs may become more apparent. When first-line therapies are not adequate, other alternative therapies should be explored. This case of MG as an irAE shows that rituximab can provide a potential benefit to treating patients with immunotherapy-induced MG who are refractory to other standard treatments. Prospective studies are needed to further evaluate the efficacy of rituximab in the management of irAEs.

Severe immune effector cell-associated neurotoxicity syndrome (ICANS) occurs in about 30% of all patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel). There are currently limited treatment strategies other than the standard corticosteroids, and it is essential to find additional therapies to manage severe ICANS. We conducted a retrospective study of neurologic outcomes among patients who received axi-cel for LBCL from May 2015 to February 2019. We identified patients who developed severe ICANS and were treated with glucocorticoids followed by intravenous immunoglobulin (IVIG) (n = 9) or glucocorticoids alone (n = 10). There was no statistically significant difference in the time to resolution (TTR) of severe ICANS between groups; however, patients in the IVIG had more severe grades of ICANS with a lower performance status at baseline. The cumulative steroid days were 11.2 in the IVIG arm and 13.5 in the glucocorticoids-only arm. The use of IVIG for severe ICANS after axi-cel therapy was tolerable and safe and is generally recommended in the CAR-T setting in patients with hypogammaglobinemia. The use of IVIG as a potential therapeutic agent for severe ICANS can be further explored in future prospective studies.

Introduction: Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. Checkpoint inhibition is the mainstay of treatment in metastatic melanoma. More recently combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed-death-1 (PD-1) blockade has resulted in improved response rates and overall survival in treatment naïve patients. Neurological toxicities are an emerging consequence of the use of checkpoint inhibitors. We are here to present a case of neurotoxicity from the use of immunotherapy. Case Report: A 63-year-old female with metastatic melanoma to brain and breast presented to the emergency department with altered mental status. She was disoriented to time and place and unable to follow commands. She had received two doses of immunotherapy with ipilimumab and nivolumab. Her last dose was administered two weeks prior. She developed low grade fever and fatigue over the past week prompting evaluation by her local oncologist who prescribed her sulfamethoxazole-trimethoprim for possible urinary tract infection. She never picked up the prescription and two days later she went to an urgent care for worsening lethargy and fever. An infectious workup was negative. She presented to our emergency department with incoherent speech and inability to comprehend. Infectious workup was again negative. Her labs were unremarkable except for hyponatremia with sodium of 123 mmol/L. A computed tomography (CT) scan of the head was negative. Magnetic resonance imaging (MRI) of the brain was done and the report did not show the previously noted brain lesions. Neurology was consulted and an electroencephalography (EEG) was done showing frequent temporal intermittent rhythmic activity (TIRDA) in the right hemisphere consistent with a tendency for seizures. There were no ictal discharges but EEG did show moderate diffuse nonspecific encephalopathy. Lumbar puncture was negative for any viral etiologies such as herpes simplex along with cell counts that were in normal range. She was started on levetiracetam and methylprednisolone 2 mg/kg daily. Within 24 hours of initiating steroids and prior to her sodium correcting, she became alert and oriented with improved ability to follow commands. After 48 hours of steroids and antiepileptic treatment, a repeat EEG was done which showed no abnormal activity. She was monitored for four more days in hospital with eventual return to her baseline. Conclusion: Counseling patients receiving immunotherapy to report any new symptoms promptly is imperative as early identification of immune-mediated adverse events leads to better outcomes. Providers should have a high index of suspicion for immune-mediated adverse events in all patients on immunotherapy presenting with new symptoms. Early identification of an immune-mediated adverse event is crucial for better patient outcomes.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 25–30% of NHL cases. The treatment is based upon stage and extent of disease. In most cases, NHL is treated with systemic chemotherapy and sometimes also radiation. As it is well known, there are numerous side effects to chemotherapy that includes rituximab. We are here to present one rare side effect of treatment called posterior reversible encephalopathy syndrome (PRES). Case Report: This is a 67-yearold female patient with diffuse large B-cell lymphoma with extensive neoplastic involvement of the lower thorax, abdomen, pelvis, and bilateral hydronephrosis with diffuse tumor infiltration of the left renal hilum. She was started on aggressive chemotherapy with dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab (DAEPOCH- R). She was also being treated with intrathecal chemotherapy with methotrexate (MTX). She presented to the emergency room with generalized weakness, confusion, and fevers. She started complaining of loss of vision in the emergency room. A quick ophthalmic examination showed that her pupils were round, regular, and reactive to light with no gross deficits. Computed tomography (CT) of the head demonstrated bilateral, symmetrical vasogenic edema in the right and left posterior frontoparietal and occipital cortices and cerebellar hemispheres. Magnetic resonance imaging (MRI) of the brain showed vasogenic edema in the cerebellum and parieto-occiptal lobes with no restricted diffusion consistent with PRES. Conclusion: Posterior reversible encephalopathy syndrome can result from various etiologies of which hypertensive encephalopathy, thrombotic thrombocytopenic purpura, and eclampsia are common. This case serves to raise awareness among hospitalists that PRES should be a differential diagnosis in the setting of patients receiving certain chemotherapeutic agents presenting with the aforementioned clinical symptoms.