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Título

Title: PAI-1 inhibitor gene 4G5G polymorphism in the context of recurrent stroke as a differential diagnosis of relapsing-remitting Multiple Sclerosis.

RESUMO

Case Report 1: Woman, 40 years old, in 2017 had a visual blurring in the left eye upon waking up, and her brain CT scan suggested stroke. Due to further motor deficit, brain MRI was performed and were observed multiple hyperintense focal lesions on T2/FLAIR in white matter, one of them enhanced contrast. CSF analysis, cervical and dorsal spinal cord MRIs were normal. A screening for microvascular disease, autoimmune diseases, bacterial/viral infections and hereditary and acquired thrombophilia were negative. In 2019, she presented motor aphasia and a new brain MRI showed a left frontal ischemic lesion. In 2020 it evolved transient stroke episodes. An investigation for thrombophilia causes, a mutation in the polymorphism in the PAI-1 gene, 4G allele, was detected.
Case report 2 – A woman, 26-year-old in December 2020 had sequential generalized motor seizures, a brain CT scan showed right cortical and subcortical hypodensity with signs of subarachnoid bleeding. He remained with mild right hemiparesis. A control MRI showed areas of right parietal encephalomalacia, with hemosiderin residues, and multiple small hyperintense focal lesions on T2 and Flair in white matter, some of them with apparent enhancement by gadolinium, suggesting demyelination. The CSF analysis showed positive oligoclonal bands. Cervical and dorsal spinal cord MRI, visual and somatosensory evoked potentials were normal. An investigation for polymorphic alteration of the PAI-1 inhibitor gene, configured as 4G5G, was detected.
Discussion: In PAI-1, the 4G allele, suppresses fibrinolysis by inhibiting tPA and uPA, plasminogen activating enzymes, thereby suppressing plasmin formation. Normal polymorphism is 5G/5G. The 4G5G and 4G4G polymorphic presentations are associated with cardiovascular thrombotic conditions and cerebral infarctions The clinical relevance of PAI-1 has been documented in several clinical and laboratory studies (1,2) Cases of Multiple Sclerosis, an inflammatory disease, may include fibrinolysis disorders in its pathogenesis.(3) The increased presence of the PAI-1 inhibitor, through polymorphism with 4G alleles, can destabilize the clinical picture, inducing infarctions and ischemia.
Comments: the participation of these polymorphisms may have contributed to the neurological conditions presented by the patients and may be a confounding or intensifying factor in the development of Multiple Sclerosis and other diseases that course with thrombosis.(4,5)