Description of neurotoxicity in a series of patients treated with CAR T-cell therapy.

Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1-2 severity and 34% had grade 3-4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3-4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.

Retinal Vessel Diameters and Physical Activity in Patients With Mild to Moderate Rheumatic Disease Without Cardiovascular Comorbidities.

Objectives: Low-grade systemic inflammation is responsible for atherosclerotic lesions in patients with rheumatic diseases. Vascular dysfunction is a precursor of atherosclerosis and can be improved by physical activity (PA). Our aim was to asses micro- and macrovascular function as well as PA and cardiorespiratory fitness (CRF) in patients with rheumatic diseases in the absence of cardiovascular (CV) comorbidities compared to controls. Methods: Fifty-one patients without CV comorbidities were compared to 35 controls. Retinal microvascular diameters were assessed using a Retinal Vessel Analyzer. Arterial stiffness (AST) was measured by applanation tonometry. CRF was assessed as peak oxygen consumption and PA was assessed with a questionnaire. Results: Retinal venular diameters were significantly wider in patients [median 221 µm (interquartile range (IQR) 211, 231)] compared to controls [median 215 µm (IQR 196, 223); p = 0.01]. One hour increase of PA per week led to a venular constriction of -0.56 µm (95%CI -1.09, -0.03; p = 0.04). In our patients with low disease activity (median DAS28 1.9; median BASDAI 2.8), no differences in AST were evident compared to controls. The association of PA and CRF with AST was not independent of blood pressure. Conclusions: Patients with rheumatic disease and mild-to-moderate disease activity show an impairment of the retinal microvasculature but not of large artery stiffness. Retinal vessel analysis seems to be a sensitive biomarker to unmask vascular impairments even in the absence of classic CV risk factors. PA may have the potential to counteract the development of small artery disease at early stages of rheumatic disease.

Chronic pseudo-angina left precordial chest pain caused by a thoracic meningioma.

Left precordial chest pain (LPCP) evokes above all angina. Eliminating a cardiac origin is then always the first priority. When cardiac causes are eliminated, non-cardiac causes are sought in order to avoid leaving patients with undiagnosed or undifferentiated chest pain. There is a myriad of non-cardiac causes ranging from heartburn, panic attacks, pleurisy, pulmonary embolism, pneumothorax, Tietze syndrome, bruises and fractures of the ribs, to spine meningioma, neuroma, herniated disk and impairment of the nerve roots. Although clinical presentation and characteristics of the pain are usually helpful in diagnosing the cause, conducting magnetic resonance imaging of the spine may be of a high utility in some situations. Here we report a case of chronic angina-like LPCP, caused by a thoracic meningioma. .

Atypical propriospinal myoclonus with possible relationship to alpha interferon therapy.

We report on a man who received interferon-alpha 2a therapy for kidney cancer and who subsequently developed propriospinal myoclonus. The myoclonus was noted at rest and during movement. The jerks were reinforced by cutaneous stimuli and tendon taps and spread to the spinal cord via polysynaptic propriospinal pathways. Cerebrospinal fluid analysis, spinal cord magnetic resonance imaging, electroencephalogram with back-averaging, and somatosensory-evoked potentials were normal. No antineuronal antibodies were found. Although the mechanism of interferon neurotoxicity remains unclear, the possible responsibility of interferon was considered, as no focal lesion or paraneoplastic pathology were disclosed.