Case Report: Findings Suggestive of Paraclinical Progressive Multifocal Leukoencephalopathy and Lung Cancer-Derived Brain Metastases in an MS Patient Treated With Fingolimod

Abstract

Fingolimod represents a highly effective disease-modifying drug in patients with active relapsing-remitting multiple sclerosis (RRMS). Its immunosuppressive effects can mediate adverse events like increased risk of cancer development or appearance of opportunistic infections. Progressive multifocal leukoencephalopathy (PML)–representing a severe opportunistic infection–has been only infrequently described during Fingolimod treatment. Here, we present a case of a 63-year-old women with pre-diagnosed RRMS who presented with new multiple cerebral lesions in a routine MRI scan, also including a tumefactive lesion in the left parietal lobe, eventually leading to the diagnosis of brain metastases derived by an adenocarcinoma of the lung. Additionally, a JCV-DNA-PCR in the cerebrospinal fluid revealed positive results, corresponding to a paraclinical progressive multifocal leukoencephalopathy. In conclusion, adverse events potentially associated with immunosuppression can occur during Fingolimod treatment. In this context, the occurrence of cancer and opportunistic infections should be carefully monitored. Here, we report a case in which JCV-DNA-PCR in the cerebrospinal fluid suggests asymptomatic PML and simultaneously lung cancer brain metastases developed. While it is rather unlikely that either event occurred as an adverse event of fingolimod treatment, a contributing effect cannot be formally excluded.

Cerebral Autoregulation in Subarachnoid Hemorrhage

“…Fingolimod is approved to treat multiple sclerosis (308) and has been clinically tested in small trials involving acute cerebral stroke (309) and intracerebral hemorrhage (310). While these stroke trials did not observe adverse effects associated with treatment (309,310), fingolimod is known to be immunosuppressive and is associated with several adverse effects, including infections, elevated liver enzymes, central nervous system effects [e.g., headache, dizziness and in some cases, leukoencephalopathy (311)] and cardiac effects (bradycardia and atrioventricular block) (308). The immunosuppression and known adverse effects have likely deterred fingolimod's use in SAH clinical trials.…”

Progressive multifocal leukoencephalopathy and sphingosine 1-phosphate receptor modulators used in multiple sclerosis: an updated review of literature

“…A total of 24 cases of PML in MS patients being treated with fingolimod were identified from 12 articles after excluding duplicate cases (see Supplemental table S1) [18,[32][33][34][35][36][37][38][39][40][41][42]. (The mean age of the patients at the time of diagnosis of PML was 50.9 ± 11.5 years (range 27-75 years) and 75% were women.…”