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In addition to combined central and peripheral demyelination, other immune diseases could involve both the central nervous system (CNS) and peripheral nervous system (PNS).To identify immune-mediated diseases responsible for symptomatic combined central/peripheral nervous system involvement (ICCPs), we conducted a multicentric retrospective study and assessed clinical, electrophysiological, and radiological features of patients fulfilling our ICCP criteria.Thirty patients (20 males) were included and followed during a median of 79.5 months (interquartile range [IQR] = 43-145). The median age at onset was 51.5 years (IQR = 39-58). Patients were assigned to one of four groups: (i) monophasic disease with concomitant CNS/PNS involvement including anti-GQ1b syndrome (acute polyradiculoneuropathy + rhombencephalitis, n = 2), checkpoint inhibitor-related toxicities (acute polyradiculoneuropathy + encephalitis, n = 3), and anti-glial fibrillary acidic protein astrocytopathy (subacute polyradiculoneuropathy and meningoencephalomyelitis with linear gadolinium enhancements, n = 2); (ii) chronic course with concomitant CNS/PNS involvement including paraneoplastic syndromes (ganglionopathy/peripheral hyperexcitability + limbic encephalitis, n = 4); (iii) chronic course with sequential CNS/PNS involvement including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome (polyradiculoneuropathy + strokes, n = 2), histiocytosis (polyradiculoneuropathy + lepto-/pachymeningitis, n = 1), and systemic vasculitis (multineuropathy + CNS vasculitis/pachymeningitis, n = 2); and (iv) chronic course with concomitant or sequential CNS/PNS involvement including combined central and peripheral demyelination (polyradiculoneuropathy + CNS demyelinating lesions, n = 10) and connective tissue diseases (ganglionopathy/radiculopathy/multineuropathy + limbic encephalitis/transverse myelitis/stroke, n = 4).We diagnosed nine ICCPs. The timing of central and peripheral manifestations and the disease course help determine the underlying immune disease. When antibody against neuroglial antigen is identified, CNS and PNS involvement is systematically concomitant, suggesting a common CNS/PNS antigen and a simultaneous disruption of blood-nerve and blood-brain barriers.

Little is known about the influence of Riluzole on serum neurofilament light chain (sNfL) levels, a biomarker of prognosis in amyotrophic lateral sclerosis (ALS), and variations with time of sNfL concentrations are controversial.Sera from ALS patients (n = 141) and controls (n = 33) were collected at inclusion (sNfL1) and second visit (sNfL2, mean delay 10.4 ± 8.7 months). sNfL levels, determined by single-molecule array, were compared between ALS and controls at both time points. sNfL concentration changes were compared between patients with Riluzole (w/Ril) at inclusion in the study and those who were treated by Riluzole following inclusion (w/o Ril). The factors influencing sNfL concentrations and changes were studied using linear regression and multivariate analysis.sNfL levels were higher in ALS patients than in controls at the two time points (p 0.00001). In ALS patients, sNfL concentrations were higher in females for both sNfL1 (p = 0.014) and sNfL2 (p 0.001). In the whole ALS group, sNfL levels were higher at sNfL2 than at sNfL1 (p 0.001). sNfL1 and sNfL2 concentrations were similar between the two ALS subgroups (w/ and w/o Ril). ALS functional rating scale-revised rate of decline and gender were the two main factors significantly influencing both sNfL1 and sNfL2 levels (p 0.01). However, only gender was shown to significantly influence sNfL changes with time (p = 0.003).In this study, sNfL levels increased with time in ALS patients and there was no difference between subjects already treated by Riluzole and those treated after sNfL1. Further studies with larger population samples and different sampling intervals are warranted to better determine the real potential of sNfL measurement as a tool to monitor treatment response in ALS.

Background and ObjectivesChimeric 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.MethodsPatients 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.ResultsThirty-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).DiscussionFIRDA 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 EvidenceThis 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.

Sjögren's syndrome (SS) and ANCA-associated vasculitis (AAV) have distinct clinical presentation and evolution, with paucity of reports on overlap syndrome. We aimed to better characterize this entity.We report four additional cases from the Montpellier university hospital. We also performed a systematic literature review, according to PRISMA guidelines, in Medline, Embase, Web of science, Cochrane Library, and grey literature. Demographic, clinical, and paraclinical data on SS and AAV were analysed.A total of 3133 articles was identified in databases, with 2695 articles screened for eligibility. After exclusion, we had 30 articles on 40 patients to analyse, in addition to 4 patients from our local recruitment (44 patients overall). Patients were female in 81.8%, with median age at AAV onset of 63.5 years. All patients but one presented with SS before, or concomitantly to the diagnosis of AAV, with a median delay of 12 months between both diagnoses. AAV predominantly had renal involvement (35/44 patients, 79.5%), anti-MPO antibodies being the most frequent (35 patients), even in patients presenting with granulomatosis with polyangiitis. We observed significantly more Raynaud phenomenon and associated auto-immune diseases in the group of non-granulomatous AAV (10 patients versus 1, p = 0.015 and 8 patients versus 0, p = 0.013, respectively).This is the largest descriptive study on the association between SS and AAV, providing information on this challenging diagnosis and interplay between these two diseases. Particular attention should be paid in the first months after diagnosis, given the specific complications and outcomes of each disease.