Background and objectives: Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS.Methods: Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS.Results: Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55-74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4-8). The median ICANS grade was 2 (1-3). Higher C-reactive protein peak (146 mg/L [86-256], p = 0.004) at day 4 (3-6), lower natremia (131 mmol/L [129-132], p = 0.005) at day 5 (3-6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA (p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS (p = 0.043).Discussion: FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results.Classification of evidence: This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy.

Abstract Background The diagnosis of breast cancer (BC)-related leptomeningeal metastases (LM) relies on the detection of tumor cells in cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, the sensitivity of this technique is low. Our goal was to evaluate whether circulating tumor cell (CTC) detection in CSF using the CellSearch® system could be used for LM diagnosis. Methods This prospective, monocentric study included adult patients with suspected BC-related LM. The clinical sensitivity and specificity of CTC detection in CSF for LM diagnosis were calculated relative to conventional CSF cytology. Results Forty-nine eligible patients were included and 40 were evaluable (CTC detection technical failure: n = 8, eligibility criteria failure: n = 1). Cytology was positive in 18/40 patients. CTCs were detected in these 18 patients (median: 5824 CTC, range: 93 to 45052) and in 5/22 patients with negative cytology (median: 2 CTC, range: 1 to 44). The detection of ≥1 CSF CTC was associated with a clinical sensitivity of 100% (95% CI, 82.4–100) and a specificity of 77.3% (95% CI, 64.3–90.3) for LM diagnosis. HER2+ CTCs were detected in the CSF of 40.6% of patients with HER2− BC (median: 500 CTC, range: 13 to 28 320). Conclusions The clinical sensitivity of CTC detection in CSF with the CellSearch® system for LM diagnosis is higher than that of CSF cytology. CTC detection in patients with negative cytology, however, must be further investigated. The finding of HER2+ CTCs in patients with HER2− BC suggests that the HER2 status of LM should be evaluated to increase the treatment opportunities for these patients.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease with frequent neurological involvement. Memory complaints are common, but their precise patterns remain unclear. We wanted to characterize patterns of neurocognitive profiles in pSS patients with cognitive complaints. Only pSS patients with memory complaints were included, prospectively. Cognitive profiles were compiled through a comprehensive cognitive evaluation by neuropsychologists. Evaluations of anxiety, depression, fatigue, sleep disorders and quality of life were performed for testing their interactions with cognitive profiles. All 32 pSS patients showed at least borderline cognitive impairment, and 17 (53%) exhibited a pathological cognitive profile: a hippocampal profile (37%), a dysexecutive profile (22%), and an instrumental profile (16%) (possible overlap). Regarding the secondary objectives: 37% of patients were depressed, and 48% exhibited a mild-to-severe anxiety trait. Sleep disorders were frequent (excessive daytime sleepiness (55%), high risk for sleep apnea (45%), and insomnia (77%)). Cognitive impairments could not be explained alone by anxiety, depression or sleep disorders. Fatigue level was strongly associated with sleep disorders. Our study highlights that cognitive complaints in pSS patients are supported by measurable cognitive impairments, apart from frequently associated disorders such as depression, anxiety or sleep troubles. Sleep disorders should be screened.

Patients with multiple sclerosis (MS) show a diffuse cerebral perfusion decrease, presumably related to multiple metabolism and vascular alterations. It is assumed that white matter fiber alterations cause a localized cerebral vasoreactivity (CVR) disruption through astrocytes metabolism alteration, leading to hypoperfusion. We proposed to (1) evaluate the CVR disruptions in MS, (2) in relation to white matter lesions and (3) compare CVR disruptions maps with standard imaging biomarkers. Thirty-five MS patients (10 progressive, 25 relapsing-remitting) and 22 controls underwent MRI with hypercapnic challenge, DTI imaging and neuropsychological assessment. Areas with disrupted CVR were assessed using a general linear model. Resulting maps were associated with clinical scores, compared between groups, and related to DTI metrics and white matter lesions. MS patients showed stronger disrupted CVR within supratentorial white matter, linking the left anterior insula to both the precentral gyrus and the right middle and superior frontal gyrus through the corpus callosum (P < 0.05, FWE corrected). Patient's verbal intellectual quotient was negatively associated with a pathway linking both hippocampi to the ispilateral prefrontal cortex (P < 0.05, FWE corrected). Disrupted CVR maps unrelated to DTI metrics and white matter lesions. We have demonstrated for the first time that white matter alterations can be indirectly identified through surrounding vessel alterations, and are related to clinical signs of MS. This offers a new, likely independent marker to monitor MS and supports a mediator role of the astrocytes in the fibers/vessels relationship.

Intracranial vasculopathies are routinely investigated by lumen-based modalities such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), and digital subtraction angiography (DSA). These techniques are useful to analyze the vessel lumen, allowing to detect vessel stenosis or occlusion. However, the primum movins of the disease, i.e., an abnormal thickening of the vessel wall, remains within the arterial wall. The vasculopathy can moreover be present without always narrowing the lumen or modifying its regularity. Hence, there is a need to detect directly and analyze vessel wall abnormalities. Development of 3D high-resolution black blood sequences for intracranial vessel wall MR imaging (VW-MRI) enabled routine clinical applications not only vasculitis, but also of intracranial atherosclerotic disease (ICAD), intracranial dissections, reversible intracranial dissections, reversible cerebral vasoconstriction syndrome (RCVS), Moyamoya disease, and intracranial aneurysms. This high-resolution intracranial VW- MRI approach is increasingly used on a clinical basis at many centers to solve diagnostic problems, especially in patients with ischemic stroke or intracranial hemorrhage. An expert consensus Guideline from the American Society of Neuroradiology provides recommendations for clinical implementation of intracranial vessel wall MRI. There are several technical aspects needed to be considered when implementing VW-MRI in intracranial vessels, including flow suppression, both in blood and cerebrospinal fluid (CSF), spatial resolution and signal-to-noise ratio (SNR). In this article, we review the technical aspects of VW-MRI, and recommend applications for vascular diseases including non-occlusive intracranial vasculopathies, Moyamoya disease, and identifying culprit plaques. We also give a focus on the utility of VW-MRI for determining stroke etiology in adults and in children and young adults.

Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.

Chronic subjective tinnitus is a widespread disorder. This perceptual anomaly is assumed to result from a dysbalance of excitatory and inhibitory mechanisms on different levels of the auditory pathways. However, the brain areas involved are still under discussion. Using resting-state functional magnetic resonance imaging, we investigate differences in cerebral regional homogeneity (ReHo) between patients with unilateral chronic tinnitus and nontinnitus control subjects. To our knowledge, our study is the first to investigate the intraregional connectivity of patients with unilateral tinnitus in relation to hearing loss. Our analyses, based on strict recruitment and characterization of the participants, showed reduced ReHo in the primary auditory cortex contralateral to the side of the perceived tinnitus percept in patients. Reduced ReHo in this same region was also correlated with increased Tinnitus Handicap Inventory and Visual Analogue Scale for loudness scores, reflecting an alteration of synchronization in this region related to the perceived loudness of the tinnitus and the related distress. Furthermore, increased ReHo in the supramarginal and angular gyri ipsilateral to the tinnitus side was correlated with increased tinnitus duration and hearing threshold at the tinnitus pitch. The correlations observed in these brain areas, which are normally related to the nontinnitus ear, could highlight compensatory mechanisms in these secondary auditory regions.