Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients.

OBJECTIVE: Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI). METHODS: A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262). RESULTS: Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4-20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs). CONCLUSION: ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

Assessing Sustained B-Cell Depletion and Disease Activity in a French Multiple Sclerosis Cohort Treated by Long-Term IV Anti-CD20 Antibody Therapy.

Few studies have investigated sustained B-cell depletion after long-term intravenous (IV) anti-CD20 B-cell depleting therapy (BCDT) in multiple sclerosis (MS) with respect to strict and/or minimal disease activity. The main objective of this study was to investigate how sustained B-cell depletion after BCDT influences clinical and radiological stability as defined by "no evidence of disease activity" (NEDA-3) and "minimal evidence of disease activity" (MEDA) status in MS patients at 12 and 18 months. Furthermore, we assessed the frequency of serious adverse events (SAE), and the influence of prior lymphocytopenia-inducing treatment (LIT) on lymphocyte subset counts and gammaglobulins in MS patients receiving long-term BCDT. We performed a retrospective, prospectively collected, study in a cohort of 192 MS patients of all clinical phenotypes treated by BCDT between January 2014 and September 2021. Overall, 84.2% and 96.9% of patients attained NEDA-3 and MEDA status at 18 months, respectively. Sustained CD19+ depletion was observed in 85.8% of patients at 18 months. No significant difference was observed when comparing patients achieving either NEDA-3 or MEDA at 18 months and sustained B-cell depletion. Compared to baseline levels, IgM and IgG levels on BCDT significantly decreased at 6 months and 30 months, respectively. Patients receiving LIT prior to BCDT showed significant CD4+ lymphocytopenia and lower IgG levels compared to non-LIT patients. Grade 3 or above SAEs were rare. As nearly all patients achieved MEDA at 18 months, we suggest tailoring IV BCDT after 18 months given the occurrence of lymphocytopenia, hypogammaglobulinemia, and SAE after this time point.

Biology of subjective cognitive complaint amongst geriatric patients: vitamin D involvement.

BACKGROUND: Insufficiency in vitamin D, a neurosteroid hormone, is associated with cognitive decline in older adults. The impact on the subjective perception of cognitive decline has not yet been examined. The objective of this cross-sectional hospital-based study was to determine whether vitamin D insufficiency was associated with subjective cognitive complaint amongst geriatric patients. METHODS: Ninety-nine consecutive Caucasian in- and outpatients recruited in the 'Cognition and LIPophilic vitamins' (CLIP) study, who had no advanced cognitive disorders (i.e., Mini-Mental State Examination score≥20) and who took no vitamin D supplements, were categorized into 2 groups based on vitamin D insufficiency (i.e., serum 25-hydroxyvitamin D≥75 nmol/L). Subjective cognitive complaint was examined using the Memory Complaint Questionnaire (MAC-Q; score 0-30, best). MAC-Q score<15 out of 30 defined severe cognitive complaint. Age, gender, body mass index, education level, comorbidity burden, functional autonomy, mood, and serum concentrations of parathyroid hormone, calcium, thyroid-stimulating hormone and vitamin B12, and estimated glomerular filtration rate were used as potential confounders. RESULTS: Compared to participants with serum 25OHD>75 nmol/L, those with vitamin D insufficiency (n=89) had a lower mean MAC-Q score (14.9±2.9 versus 17.1±1.6, P=0.02) and more often a MAC-Q score<15 (52.8% versus 10.0%, P=0.01). Vitamin D insufficiency was inversely associated with the MAC-Q score (adjusted ß=-2.84, P=0.03), and positively associated with severe cognitive complaint (adjusted OR=10.07, P=0.03). CONCLUSION: Vitamin D insufficiency was associated with subjective cognitive complaint in the studied cohort of geriatric patients.