Nathoo, Nabeela

Background: Gender-affirming hormone therapy (GAHT) may increase multiple sclerosis (MS) risk, yet MS disease course among transgender and gender-diverse (TGD) individuals remains understudied. We aimed to evaluate the disease course in TGD individuals with MS (TGD-MS). Methods: Seventeen TGD-MS were identified. Ten TGD-MS on GAHT (five transgender women with MS (TW-MS) and five transgender men with MS (TM-MS)) were investigated further for MS outcomes of symptomatic (clinical)/asymptomatic (radiological) disease activity and progressive MS (PMS) onset. Results: TW-MS (mean = 54.5 years, range = 35.1–66.3) were older than TM-MS (39.2 years, range = 29.6–47.2) at last follow-up. MS onset was later in TW-MS (31.5 years, range = 25.1–39.1) than in TM-MS (21.0 years, range = 15.0–29.8). Three patients (one TW-MS, two TM-MS) experienced symptomatic activity after GAHT initiation (8–10 months); in two patients (one TW-MS, one TM-MS), this marked symptomatic MS onset. Seven patients (four TW-MS, three TM-MS) had ⩾1 clinical/radiological disease activity. Four had PMS; all were TW-MS. In three, GAHT initiation preceded PMS onset (1–5 years). Disability was higher in TW-MS than in TM-MS. Conclusion: MS disease course may be modified by GAHT and may differ between TW-MS and TM-MS, highlighting the need for larger long-term studies to overcome disparities in MS care. Comprehensive GAHT history, timely management, and closer follow-up are warranted in TGD-MS.

This international multicenter study seeks to determine the frequency and characteristics of meningitis in myelin oligodendrocyte glycoprotein antibody (MOGAD)–associated disease and highlight its pathology.

Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women. Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS). Methods: In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCC brain ) was obtained. Impact of sex and menopause on UCC brain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated. Results: UCC brain was smaller in pwMS ( n = 118, 51.4 ± 5.3 mm 2 ) than controls ( n = 118, 54.2 ± 4.4 mm 2 , p < 0.001) and inversely correlated with older age in pwMS ( r = −0.24, p = 0.010) but not in controls ( r = −0.025, p = 0.786). In 173 pwMS (413 brain MRIs), UCC brain was smaller in men (49.5 ± 5.9 mm 2 ) than women (51.6 ± 5.5 mm 2 , p = 0.001), postmenopausal women (49.4 ± 5.6 mm 2 ) than premenopausal women (52.9 ± 4.1 mm 2 , p < 0.001), and progressive (47.5 ± 5.6 mm 2 ) than relapsing MS (52.1 ± 5.2 mm 2 , p < 0.001). UCC brain also correlated with disease duration ( r = −0.39, p < 0.001), 9-hole peg test ( r = −0.26, p = 0.005), and severe ambulatory disability (Expanded Disability Status Scale ⩾6) ( r = −0.27, p < 0.001). Conclusion: UCC brain , a biomarker of progressive MS, is inversely associated with age, disease duration, male sex, and menopause, highlighting the potential impact of sex and hormones on neurodegeneration in MS.

AbstractBackgroundCrystal‐storing histiocytosis (CSH) is a rare form of histiocytosis with intralysosomal accumulations of immunoglobulins or paraproteins that aggregate as crystals. Central nervous system (CNS) involvement of CSH is uncommon but should be considered in cases of persistent parenchymal enhancement on neuroimaging.MethodsWe describe one local case of CNS CSH and 10 additional cases identified by literature review.ResultsAmong 11 CSH patients, lesions involved either the dura (2/11) or brain parenchyma (9/11). Two cases had leptomeningeal enhancement. One case had spinal cord involvement. Two cases were associated with marginal zone lymphoma; one case was associated with an immunoglobulin A‐plasma cell dyscrasia. Eight of 11 cases had outcome data available: 7/8 cases had clinical and/or radiological improvement and 1/8 had radiological stability.ConclusionsCentral nervous system involvement of CSH is rare. Potential cases should be comprehensively evaluated for lymphoma or myeloma with positron emission tomography/computed tomography (CT) of the body or alternatively, CT of the chest, abdomen, pelvis and nuclear bone scan, bone marrow biopsy, serum protein electrophoresis, and cerebrospinal fluid protein electrophoresis. Treatment is targeted toward the underlying malignancy.

Introduction: Fanconi anemia (FA) is an inherited condition associated with genetic mutations that affect DNA repair proteins. More than 20 genes involved in the FA/BRCA pathway have been implicated in FA, including BRIP1. Tumefactive brain lesions are rare in FA. Case Report: We describe a patient with FA and recurrent tumefactive brain lesions preceded by calcifications on head computed tomography. A biopsy revealed white-matter gliosis with severe vasculopathy. Whole-genome sequencing demonstrated a BRIP1 homozygous variant with a final diagnosis of recurrent tumefactive brain lesions due to BRIP1-associated CNS vasculopathy. Immunosuppressive treatment was ineffective in the present case. Conclusions: Mechanistically, the specific role of BRIP1 mutation in CNS inflammation and vasculopathy is unclear. However, immunodeficiency disorders can lead to autoimmunity and/or immune dysregulation due to the possible loss or gain of function of components of the immune system.