Impact of adult-onset multiple sclerosis on MRI-based intracranial volume: A study in clinically discordant monozygotic twins.

OBJECTIVE: Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS. METHODS: FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV. RESULTS: 54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10-5). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003). CONCLUSION: We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.

Incidence, clinical spectrum, and immunotherapy of non-ischemic cerebral enhancing lesions after endovascular therapy.

BACKGROUND: Symptomatic and asymptomatic delayed non-ischemic cerebral enhancing (NICE) lesions in magnetic resonance imaging (MRI) have been reported as a rare complication after endovascular therapy (EVT) in recent years with incidence rates between 0.05% and 0.9% in most studies. Information on long-term clinical course and immunotherapies is scarce or has not been reported in detail in the literature. Objective: Aims of our study were to assess the incidence of NICE lesions in patients after cerebral EVT over a period of more than 12 years, describe clinical and EVT characteristics, and immunotherapies applied. METHODS: A retrospective chart review of all patients treated by endovascular therapy for symptomatic or asymptomatic aneurysms at the University Hospital of Augsburg from May 1, 2008 to December 31, 2020 was performed. Patients were identified retrospectively and followed-up prospectively where appropriate. In addition, one case treated at another institution was included. RESULTS: Five out of 746 patients, 0.67%, developed NICE lesions after EVT, all with non-ruptured aneurysms and all symptomatic upon detection of NICE lesions by MRI. In total, the disease course of 6 female patients is reported. Symptoms occurred after a mean time of 15 days (±13.42, SD) after EVT with headache (6/6 patients), focal neurological signs (6/6 patients), epileptic seizures (2/6 patients) and cognitive deficits (3/6 patients). All 6 patients received glucocorticosteroids (GCS), 1/6 azathioprine (AZA), 4/6 mycophenolate mofetil (MMF), 1/6 methotrexate (MTX), 1/6 rituximab (RTX), 2/6 cyclophosphamide (CYC) and 3/6 tocilizumab (TCZ). A treatment response could be observed for GCS, TCZ and MMF (in two of four cases), RTX and AZA did not result in disease stabilization. CONCLUSIONS: Delayed NICE lesions are a rare complication after EVT, requiring immunotherapies in all patients reported here. Physicians should be aware of this disorder in case of new symptoms or contrast enhancing lesions after EVT.