Neuronal apoptosis induced by cerebrospinal fluid from multiple sclerosis patients correlates with hypointense lesions on T1 magnetic resonance imaging

Abstract

Neuronal damage seems to be a major source of disability in multiple sclerosis (MS) patients and at present magnetic resonance imaging (MRI) is a sensitive method to evaluate lesion and disease activity. We studied the potential correlation between changes in MS patients' disability after relapse, the degree of T1 lesion hypointensity on MRI in vivo and neuronal apoptosis induced by cerebrospinal fluid (CSF) on neuron cultures. In this study, we included 24 MS patients with relapsing disease. Clinical recovery from relapse was measured by the Expanded Disability Status Scale (EDSS). T1-weighted MRI studies were done according to established standards and neuronal apoptosis was induced by treatment of neuronal cultures with CSF from patients while relapsing. Recovery after relapse is inversely correlated with neuronal apoptosis ( r=−0.725, p<0.0001). A correlation was found between T1 lesion hypointensity and a poor recovery from relapse ( r=0.656, p=0.0005) and such hypointensity correlated strongly with neuronal apoptosis ( r=−0.779, p<0.0001). CSF from all patients with hypointense T1 lesions caused significantly increased neuronal apoptosis, whereas all CSF that did not induced such effects corresponded to patients without T1 lesions. The recovery from an acute MS relapse is significantly worse in patients with hypointense T1 lesions in MRI and in those whose CSF damaged neurons on cultures in vitro, phenomena that closely correlated each other.