Eosinophilic pleocytosis in the cerebrospinal fluid following CAR-T cell therapy for CNS lymphoma: A case for warning?

INTRODUCTION: CAR-T cell therapy, emerging as an efficient treatment option for patients with secondary central nervous system (CNS) lymphoma, is frequently complicated with immune effector cell-associated neurotoxicity syndrome (ICANS). CASE PRESENTATION: We report a case of a 64-year-old woman with transformed follicular lymphoma, developing high-grade ICANS with eosinophilic pleocytosis following third-line therapy with CAR-T cells (tisagenlecleucel). During bridging therapy, she declined neurologically and was diagnosed with secondary CNS lymphoma. She received methotrexate-cytarabine-thiotepa-rituximab regimen with clinical and radiological improvement. Post-CAR-T cell infusion she developed cytokine release syndrome grade II and ICANS grade III. Given the lack of response to steroids, anakinra was initiated with complete ICANS resolution. Cerebrospinal fluid (CSF) analysis, performed only on day +10 due to thrombocytopenia, revealed eosinophils, while infections were excluded. CONCLUSION: This report emphasizes the importance of CSF analysis in individuals with CAR-T-related neurotoxicity for elucidating the role of specific immune cells in such complications.

Primary CNS vasculitis: insights into clinical, neuropathological, and neuroradiological characteristics.

Background and objectives: Primary CNS vasculitis (PCNSV) is a rare inflammatory disorder that affects the blood vessels of the central nervous system (CNS). We aimed to analyze the neurological presentations, clinical follow-up, and long-term outcomes of patients with primary central nervous system vasculitis. Methods: We conducted a retrospective analysis of medical records to assess the neurological presentation, rate of remission, and functional status at the last follow-up in patients with primary central nervous system vasculitis seen in our center in the last 13 years (2010-2023). Results: We identified five patients, whose median age at symptom onset was 31 years (range: 15-41 years), including four male individuals (80%) from Muslim Arab (n = 4) and Ashkenazi Jewish (n = 1) backgrounds. Symptoms persisted for a median of 36 weeks (range: 3 weeks to 4 years) before diagnosis, with one case exceeding 3 years. Follow-up lasted a median of 56 months (range: 20-161 months). Clinical symptoms varied, presenting unilateral weaknesses (n = 2), cognitive and gait abnormality (n = 1), headaches (n = 1), and epileptic seizures (n = 1). MRI scans revealed abnormalities in the basal ganglia, corona radiata, parietal, and frontal lobes, showing hemorrhage, vasogenic edema, restricted diffusion, and enhancement post-gadolinium. All patients reported progressive holocephalic headaches and cognitive changes with overall progressive symptoms. Initial neurological examinations revealed abnormalities in all patients and included one or more of the following: cognitive or visual impairment (n = 2), seizures (n = 1), and unilateral UMN signs (n = 2) at the initial neurological examination, all but one patient required walking aids including (cane 2, wheelchair, bedridden 1). Patients were stable (n = 2), deteriorated (n = 1), or improved (n = 2). Following treatment, two patients still required ambulatory aids, with one using a cane and the other using a wheelchair, while the remaining three did not require any ambulatory aids. Discussion: The study on PCNSV highlights varied symptoms and diagnostic challenges, including delayed diagnosis and a spectrum of neurological issues from cognitive impairments to seizures. Brain biopsies showed lymphocytic infiltration, thrombi, and necrosis. Immunotherapy significantly improved clinical and radiological outcomes. Over 56 months of follow-up, outcomes varied from stability and deterioration to improvement.

Radiological findings in poisoning by synthetic cannabinoids adulterated with brodifacoum.

OBJECTIVES: Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide hazard. Here, we review the spectrum of imaging findings in adulterated cannabinoid poisoning. MATERIALS AND METHODS: In this retrospective study, we used the Israeli Poison Information Center database to identify patients with cannabinoid-associated coagulopathy who presented to the Rambam Health Care Campus, where most patients were treated during an outbreak in northern Israel between September 2021 and June 2022. All relevant imaging studies for these patients were reviewed. We estimated the sensitivity of findings for cannabinoid-associated coagulopathy. Associations between a continuous variable and a dichotomous outcome were assessed with the Mann-Whitney U test. RESULTS: We identified 48 patients (mean age 40 years ± 9 [SD], 43 males) with 54 hospitalizations due to cannabinoid-associated coagulopathy. Symptomatic hemorrhage was documented in 50 (93%) cases at presentation, most of whom (78%) had hemorrhage from multiple systems. The most common bleeding site was the genitourinary collecting system, with a characteristic sign of suburothelial bleeding in 16/18 of performed abdominal CTs (sensitivity 89% [CI 65-99%] for cannabinoid-associated coagulopathy). Intramural bowel hematomas were noted in 70% (7/10) of CTs of patients with gastrointestinal bleeding. Incidental bleeding sites were identified on imaging in 24% of patients. An increased number of bleeding sites was associated with need for vasopressors (difference in bleeding sites 3.00 [95% CI 0.99-4.00], p = 0.026). CONCLUSION: CT plays a key role in the diagnosis and work-up of adulterated cannabinoid-associated coagulopathy. Characteristic signs include suburothelial hemorrhage and intramural bowel hematomas. CLINICAL RELEVANCE STATEMENT: Recognition of radiological signs of adulterated synthetic cannabinoid-associated coagulopathy is critical for optimizing outbreak control on the public health level and ensuring timely treatment on the individual patient level. KEY POINTS: • Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide threat. • Characteristic imaging signs include suburothelial bleeding, intramural bowel hematomas, and rare incidental bleeding sites. • Imaging has a pivotal role in optimizing outbreak control and ensuring timely and appropriate treatment.

Validation of TIRADS ACR Risk Assessment of Thyroid Nodules in Comparison to the ATA Guidelines.

OBJECTIVES: The prevalence of thyroid nodules in adults, detected by ultrasound (US), is reported as high as 68%. US-guided fine-needle aspiration biopsy (FNAB) is the test of choice used to determine the nature of the nodules. However, not more than 15% are found to be malignant. Reducing the number of unnecessary FNAB while identifying clinically significant malignant nodules is imperative. There are several guidelines suggested for risk stratification of thyroid nodules by US. The aim of our study was to validate and compare Thyroid Imaging Reporting and Data System (TIRADS) American College of Radiology (ACR) and American Thyroid Association (ATA) risk stratification, specifically pertaining to reduction of unnecessary biopsies. MATERIAL AND METHODS: The study included 281 nodules in 245 patients who underwent FNAB between May 2018 and June 2019. Statistical analysis was performed only on 235 nodules that according to the TIRADS ACR and/ or ATA guidelines were eligible for FNAB. Data collected included nodule characteristics with corresponding TIRADS and ATA grading and cytological results using Bethesda scoring. RESULTS: An agreement was found between the two criteria methods in 58.2% (137/235) of the cases. In 35.3% (83/235), ATA recommended FNAB while TIRADS did not. The specificity for ATA criteria was 7% (15/221) and for TIRADS was 37% (81/221). The sensitivity was 100% (14/14) for ATA and 86% (12/14) for TIRADS. CONCLUSION: Application of ACR TIRADS criteria can reduce the number of US-guided FNAB performed on benign nodules compared to ATA criteria, by 35%, with a cost of only two missed carcinomas that remained on further follow-up.

De novo ATP1A3 variants cause polymicrogyria.

Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.

Q fever vertebral osteomyelitis among adults: a case series and literature review.

BACKGROUND: Q fever osteoarticular infections are a rare complication of the chronic form of Q fever. We aimed to characterize chronic Q fever vertebral osteomyelitis through our experience and a review of the literature. METHODS: Four adult patients with Q fever vertebral osteomyelitis diagnosed in a tertiary hospital in northern Israel between 2016 to 2020 are described. In addition, a 30 years' literature review of Q fever vertebral osteomyelitis, characterizing predisposing factors, clinical presentation, course of disease, treatment and outcomes, was performed. RESULTS: Thirty-four adult patients with Q fever vertebral osteomyelitis were identified. The vast majority were male (30/34, 88%) with a mean age of 67.2 ± 10 years. Involvement of the adjacent aorta, likely the origin of the infection, was observed in 23/34 (68%) of the patients, usually among patients with aortic graft or aneurysm. Clinical presentation was insidious and fever was frequently absent. Delayed diagnosis for months to years after symptoms onset was frequently reported. Vascular infections were managed with or without extraction of the infected aneurysm/aorta and graft placement. The outcome was variable with limited follow-up data in most cases. Patients were usually treated with prolonged antimicrobial therapy, most commonly doxycycline and hydroxychloroquine combination therapy. CONCLUSION: Q fever should be included in the differential diagnosis of vertebral osteomyelitis in endemic settings, in particular when concomitant adjacent vascular infection exists.

Risk Factors Predicting the Necessity of Renal Ultrasound in the Emergency Department.

OBJECTIVES: Renal ultrasound (US) is widely used for diagnosing renal pathologies, though few of them, such as obstructive uropathy, require emergent urological intervention. During on-call hours, when medical staff is limited, it is important to prioritize which renal US examinations will be done. The aim of this study was to evaluate patient risk factors to predict the necessity of emergent renal US in the emergency department (ED). MATERIAL AND METHODS: All adult patients referred for renal US from the ED, during on-call hours from May 2015 to April 2017, were retrospectively included. The mean age was 64 years (18-98). Data were collected from the patients' medical records. Urological intervention performed within the first 24 h following the US examination was recorded. Multivariate analysis was performed. RESULTS: About 66% of the patients did not have a permanent urethral catheter, history of renal stones, or known abdominal or pelvic mass. None of these patients required an urgent urological intervention. The receiver operating characteristic curve was calculated at 0.883, 95% CI (0.84-0.92). CONCLUSION: Using only three variables, we can greatly reduce the number of renal US examinations done at on-call hours allowing for prioritization of only the necessary examinations.

Necrotizing sialometaplasia of the palate in a young bodybuilder with anabolic androgenic steroids abuse.

Necrotizing sialometaplasia is a benign, self-limiting, inflammatory disease of salivary glands, mainly involving the minor salivary glands in the palate. This lesion can mimic a malignant neoplasm, both clinically and histopathologically, manifesting as a submucosal swelling or as an ulcer of the palate. This report presents a case of an otherwise healthy bodybuilder with anabolic androgenic steroids abuse with bilateral necrotizing sialometaplasia in the palate, and discusses computed tomography findings in the pre-ulceration phase. Literature review revealed another two cases of necrotizing sialometaplasia with preoperative imaging, both performed in the ulceration phase. The importance of radiographic findings as an aid in differential diagnosis is further discussed, as well as the role of possible predisposing factors including anabolic androgenic steroids abuse in the pathogenesis of necrotizing sialometaplasia.