Impact of modern central nervous system radiation on multiple sclerosis relapse and progression

Background: Central nervous system (CNS) radiation is associated with primary demyelination and neurotoxicity in patients with existing demyelinating disorders. We examined the safety of modern ionizing-radiation techniques in multiple-sclerosis (MS) patients. Patients and methods: Patients with MS undergoing CNS radiation for any reason between January 2005, and August 2024 were identified by chart review. Inclusion criteria were: 1) confirmed diagnosis of MS; 2) Receiving therapeutic radiation with a dose of greater than 5 Gray (Gy) to brain or spinal cord parenchyma; 3) Clinical neurology and brain MRI follow-up available following radiation. Results: Thirty-three patients were included. Median age at radiation was 60 years (54--68 IQR) and median follow-up, 20 months (range 3-99). Radiation focused on the CNS in 15/33 (45%), 5 (15%) targeted locations adjacent to the CNS parenchyma (meningioma 4, trigeminal neuralgia 1), and 13 (39%), outside the CNS with > 5 Gy delivered to the CNS. Clinical MS course at radiation was relapsing remitting (19/33), secondary progressive (11/33), and primary progressive (3/33). Thirteen patients (39%) were on MS disease-modifying therapy. No clinical relapse or new-onset MS progression followed radiation. New T2 or gadolinium-enhancing lesions on T1 MRI occurred in 7/33. Radiation-field data were analysed with reference to location of 10 new demyelinating lesions in 7 patients. Most lesions lay outside the irradiated area (6/10). No patients with new lesions were on high-efficacy medications. Seven patients experienced increased expanded disability status scale (EDSS) pre-radiation to last follow-up by ≥ 1 point (median 1.5, range 1-7). One patient had known progressive disease while 5 patients' increased disability was thought secondary to their radiation indication (3 glioblastoma and 2 meningioma). Conclusions: Modern-day ionizing radiation to the CNS in patients with multiple sclerosis was not associated with clinical worsening but can potentially be associated with an increased risk of asymptomatic inflammatory MS disease activity.