EEG-based grading of immune effector cell-associated neurotoxicity syndrome.

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47-0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.

Unusual Movement Disorders and Atypical Magnetic Resonance Imaging (MRI) Findings in Patients with West Nile Encephalitis: Case Reports of 2 Patients with Evidence of Clinical and Imaging Resolution with IVIG.

BACKGROUND West Nile virus (WNv) is the leading cause of epidemic arbovirus encephalitis in the continental United States. Movement disorders (MDs) have been reported in 20% to 40% of patients with WNv and about 37% of patients with WNv encephalitis have changes on magnetic resonance imaging (MRI). We report 2 unusual cases of neuroinvasive WNv in patients with unusual MDs and unreported MRI findings. CASE REPORT In the first case, a 34-year-old man presented with a 1-week history of disinhibition, agitation, opsoclonus-myoclonus and ataxia syndrome (OMAS), tremor, and facial agnosia. Evaluation of his cerebrospinal fluid (CSF) revealed elevated immunoglobulin (Ig)M against WNv, a high level of protein (98 mg/dL), and an elevated white blood cell (WBC) count (134, 37% lymphocytes). An MRI of the brain showed an area of diffusion restriction in the splenium of the corpus callosum. The patient's MRI findings and OMA improved significantly after 2 treatments with i.v. IG (IVIG). In the second case, a 57-year-old woman presented with fever, headaches, psychosis, and ataxia; she was subsequently intubated for airway protection. Analysis of her CSF showed elevated IgM against WNv, a high level of protein (79 mg/dL), and elevated WBC count (106, 90% lymphocytes). One week after the onset of symptoms, the patient experienced facial dyskinesia. Later, she developed proximal bilateral lower extremity weakness. An MRI of her lumbar spine showed evidence of myeloradiculitis with contrast enhancement of the conus medullaris and ventral nerve roots. After a single treatment with IVIG, she had partial improvement in weakness. CONCLUSIONS MDs and changes on MRI have been reported in patients with neuroinvasive WNv disease. Our patient with OMAS also had transient splenial diffusion restriction on imaging, which, to the best of our knowledge, has not been previously reported with WNv infection. In both patients, treatment with IVIG resulted in improvement in symptoms.

Malignant glomus tumor of the lung with multiorgan metastases: case report and literature review.

Glomus tumor is an exceedingly rare neoplasm that is derived from cells of the neuromyoarterial glomus or glomus body. It rarely occurs in the visceral organs where glomus body may be sparse or even absent, such as the stomach, intestines, mediastinum, and respiratory tract. It is unusual for a glomus tumor to demonstrate atypical or malignant histopathological characteristics. It is also rare for such a tumor to express clinically aggressive behavior. However, when metastasis does occur, this disease is often fatal. We herein report an interesting case of a middle-age woman admitted due to progressive cough and hemoptysis. A polypoid mass was found to occlude the left lingular lobar bronchus. Final histopathologic examination showed the presence of malignant glomus tumor, confirmed by immunoreactivity for smooth muscle actin and vimentin. Two months later, the patient developed abdominal distension and gastrointestinal bleeding. Further evaluation lead to the discovery of widespread metastatic disease to the gastrointestinal tract, spleen, and the left adrenal gland. We further entail a review of the literature on the clinicopathologic features and diagnosis of this uncommon tumor.