Can fibrinolytic system components explain cognitive impairment in multiple sclerosis?

Background: The fibrinolytic system is capable of modulating inflammatory and degenerative events within the central nervous system. Specifically, the plasminogen activator inhibitor-1 (PAI-1) has been associated with different pathological conditions in multiple sclerosis (MS) and its role in cognitive functioning is also known.

Objectives and methods: To study the association between plasma levels and the polymorphic variants of the PAI-1 gene and cognitive performance in MS. 176 patients were studied. Neuropsychological evaluation was performed with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). A Polymerase Chain Reaction (PCR) was used to determine PAI-1 4G/5G polymorphisms and quantification was performed using an Enzyme-Linked ImmunoSorbent Assay (ELISA).

Results: Participants were categorized as not cognitively impaired (NCI; n=114) and cognitively impaired (CI; n=62). The NCI group had a higher percentage of heterozygous subjects but no statistical differences were found between the CI and NCI group. Neuropsychological functioning did not correlate with plasma levels of PAI-1 or its genetic polymorphism. It is noteworthy that PAI-1 plasma levels were related to neurological impairment.

Discussion: Cognitive impairment in MS is due to strategic focal lesions affecting regions and tracts involved in cognitive processes and to diffuse damage in the white and gray matter. This complex etiology could explain the absence of a relationship between the cognitive functioning and PAI-1 in patients with MS that has been found in vascular dementia or Alzheimer's disease. Plasma curves of PAI-1 and its measures in cerebrospinal fluid could help elucidate the role of PAI-1 in MS.