Multiple sclerosis relapse following gamma knife radiosurgery for meningioma in a patient treated with natalizumab: case report

Objectives We describe a case of a patient with multiple sclerosis (MS) stable on natalizumab who developed widespread gadolinium-enhancing lesions and clinical relapse seven and eight months after gamma knife radiosurgery (GKRS) for left cerebellar convexity meningioma. We explore how increased blood–brain barrier (BBB) permeability post-GKRS could potentially interfere with the lymphocyte anti-trafficking effect of natalizumab and result in new central nervous system (CNS) inflammation distant from the radiation site. Methods Comprehensive analysis of the patient’s chart, brain and spine imaging, serum and cerebrospinal fluid (CSF) profiles was conducted. We compiled a graphical representation of treatment changes, radiologic findings, and GKRS initiation within one timeframe. We conducted a structured literature review to support the discussion of this case and hypothesize possible pathophysiological mechanisms contributing to clinical and radiological findings. Results Seven months after GKRS, follow-up brain magnetic resonance imaging (MRI) demonstrated multiple gadolinium-enhancing lesions in both cerebral hemispheres, and repeat imaging one month later revealed new gadolinium-enhancing lesions, correlating with the patient’s clinical relapse. Alternative causes of disease progression, including radiation-induced demyelination, radionecrosis, opportunistic infections, progressive multifocal leukoencephalopathy (PML), and development of anti-natalizumab antibodies, were explored and considered less likely. The patient was switched to ofatumumab with subsequent clinical and radiological stability. Discussion Given extensive new inflammatory lesions far from the GKRS site, it seems unlikely that the sole mechanism was radiation-induced neurotoxicity. We hypothesize that late delayed radiation side effects caused by GKRS may have enabled peripheral lymphocytes to enter the CNS, counteracting the effects of natalizumab on blocking lymphocyte trafficking through the BBB and possibly contributing to MS relapse.