Recurrent Status Epilepticus in the Setting of Chimeric Antigen Receptor (CAR)-T Cell Therapy.

Axicabtagene ciloleucel (AC) is an FDA-approved anti-CD19 autologous chimeric antigen receptor T-cell (CAR-T) therapy for refractory diffuse large B cell lymphoma (DLBCL). While its efficacy in DLBCL has been promising, neurotoxicity remains a significant concern. We present a case of a 22-year-old woman with chemotherapy-refractory DLBCL who exhibited Grade IV neurotoxicity in the setting of sepsis, after undergoing AC infusion. Despite prophylactic levetiracetam given per guidelines,1,2 she experienced a precipitous mental status decline on post-infusion day 8 (D8) followed by hypoxic respiratory failure in the setting of clinical status epilepticus on D11 and nonconvulsive status epilepticus (NCSE) on D18. While neuroimaging was unremarkable, EEG demonstrated diffuse slowing and 2.5-3 Hz generalized periodic discharges consistent with NCSE. Seizures were initially refractory to lorazepam, increasing doses of levetiracetam, and phenobarbital, requiring a midazolam drip titrated to 50-70% burst suppression for resolution. Methylprednisolone and tocilizumab were used to treat neurotoxicity and cytokine release syndrome, respectively. Empiric antibiotics were used for sepsis. After cessation of sedatives on D19, mental status improved to near baseline. PET/CT just prior to discharge showed a complete response of the DLBCL (Deauville 3). She was discharged on D37 with no further seizure activity. Unfortunately, a 3-month interval PET/CT demonstrated disease progression which continued through salvage pembrolizumab eventually leading to death 1.2 years post-CAR-T infusion. This case illustrates the clinical management challenges of a complex and rare neurotoxic side effect of CAR-T cell therapy, namely NCSE following status epilepticus.

MELAS: Monitoring treatment with magnetic resonance spectroscopy.

BACKGROUND: To assess the utility of Magnetic Resonance Spectroscopy (MRS) as a biomarker of response to L-arginine in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). AIMS: To describe a case of MELAS treated with L-arginine that showed improvement clinically and on serial MRS METHODS: MRS was performed on a 1.5-Tesla scanner to evaluate a MELAS patient before, during, and after intravenous (IV) L-arginine therapy for the treatment of stroke-like episodes. L-arginine was infused at a dose of 500 mg/kg daily for 7 days followed by oral arginine therapy. RESULTS: The patient had clinical improvement after treatment with IV L-arginine. MRS performed before, during, and after treatment with IV L-arginine showed significant improvement in brain lactate and increase in the N-acetylaspartate/Choline (NAA/Cho) ratio compared to pre-treatment baseline. CONCLUSION: Serial MRS imaging showed significant improvement in lactate peaks and NAA/Cho ratios that corresponded with clinical improvement after L-arginine therapy. Given this correlation between radiologic and clinical improvement, MRS may be a useful biomarker assessing response to treatment in MELAS.

A Case of Sjögren's Syndrome Mimicking Inflammatory Myopathy.

Sjögren's syndrome (SS) is a chronic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands and causing the decreased function of lacrimal and salivary glands. We describe a case of a 34-year-old male who presented with Sjögren's syndrome presenting as myopathy and sensorimotor neuropathy. His creatinine kinase levels were elevated with positive anti-Sjögren's syndrome-related antigen A autoantibodies and anti-Sjögren's syndrome Type B autoantibodies. Electromyography showed evidence of irritable myopathy. Parotid gland biopsy demonstrated focal lymphocytic sialadenitis. The patient favorably responded to high-dose steroids. Thus, although rare, inflammatory myopathy must be considered part of the initial presentation of Sjögren's syndrome.

Acute cerebrovascular disease occurring after hospital discharge for labor and delivery.

BACKGROUND AND PURPOSE: The risk of stroke and other postpartum cerebrovascular disease (CVD) occurring after hospital discharge for labor and delivery is uncertain. METHODS: We performed a retrospective cohort study using administrative databases to identify all pregnant women who were hospitalized for labor and delivery at nonfederal, acute care hospitals in California from 2005 to 2011 and who were discharged without an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of CVD. The primary outcome was an acute CVD composite defined as any ischemic stroke, intracranial hemorrhage, cerebral venous sinus thrombosis, pituitary apoplexy, carotid/vertebral artery dissection, hypertensive encephalopathy, or other acute CVD occurring after hospital discharge and before 6 weeks after labor and delivery. Descriptive statistics were used to estimate the incidence of postdischarge CVD. Multivariate logistic regression was used to evaluate the association between selected baseline factors and postdischarge CVD. RESULTS: The rate of any postdischarge acute CVD was 14.8 per 100 000 patients (95% confidence interval [CI], 13.2-16.5). Risk factors for any acute CVD were eclampsia (odds ratio [OR], 10.1; 95% CI, 3.09-32.8), chronic kidney disease (OR, 5.4; 95% CI, 2.5-11.8), black race (OR, 2.5; 95% CI, 1.9-3.3), preeclampsia (OR, 2.1; 95% CI, 1.6-2.8), pregnancy-related hematologic disorders (OR, 1.8; 95% CI, 1.3-2.5), and age (OR, 1.5 per decade; 95% CI, 1.3-1.8). CONCLUSIONS: The incidence of postpartum acute CVD after hospital discharge for labor and delivery is similar to rates reported for all postpartum events in previous publications, suggesting that a substantial proportion of postpartum CVD occurs after discharge.

Risk of a thrombotic event after the 6-week postpartum period.

BACKGROUND: The postpartum state is associated with a substantially increased risk of thrombosis. It is uncertain to what extent this heightened risk persists beyond the conventionally defined 6-week postpartum period. METHODS: Using claims data on all discharges from nonfederal emergency departments and acute care hospitals in California, we identified women who were hospitalized for labor and delivery between January 1, 2005, and June 30, 2010. We used validated diagnosis codes to identify a composite primary outcome of ischemic stroke, acute myocardial infarction, or venous thromboembolism. We then used conditional logistic regression to assess each patient's likelihood of a first thrombotic event during sequential 6-week periods after delivery, as compared with the corresponding 6-week period 1 year later. RESULTS: Among the 1,687,930 women with a first recorded delivery, 1015 had a thrombotic event (248 cases of stroke, 47 cases of myocardial infarction, and 720 cases of venous thromboembolism) in the period of 1 year plus up to 24 weeks after delivery. The risk of primary thrombotic events was markedly higher within 6 weeks after delivery than in the same period 1 year later, with 411 events versus 38 events, for an absolute risk difference of 22.1 events (95% confidence interval [CI], 19.6 to 24.6) per 100,000 deliveries and an odds ratio of 10.8 (95% CI, 7.8 to 15.1). There was also a modest but significant increase in risk during the period of 7 to 12 weeks after delivery as compared with the same period 1 year later, with 95 versus 44 events, for an absolute risk difference of 3.0 events (95% CI, 1.6 to 4.5) per 100,000 deliveries and an odds ratio of 2.2 (95% CI, 1.5 to 3.1). Risks of thrombotic events were not significantly increased beyond the first 12 weeks after delivery. CONCLUSIONS: Among patients in our study, an elevated risk of thrombosis persisted until at least 12 weeks after delivery. However, the absolute increase in risk beyond 6 weeks after delivery was low. (Funded by the National Institute of Neurological Disorders and Stroke.).