Dados do Trabalho

Título

CADASIL and/or multiple sclerosis? A case of difficult diagnosis

RESUMO

Case report
A 48-year-old female was referred to our clinic for investigation of possible MS, which had started 3 years earlier with an episode of dysarthria and right lower limb weakness. MRI showed focal and confluent T2-hyperintense lesions in the subcortical and periventricular white matter as well as infratentorial regions and cervical and thoracic spinal cord. Since she lacked evidence of dissemination in time, a diagnosis of high-risk clinically isolated syndrome was made and she was started on glatiramer acetate. Over the next year, there were new symptoms accompanied by gadolinium-enhancing brain lesions. At this point she fulfilled the diagnostic criteria for MS and was treated with I.V. methylprednisolone, with improvement. She was switched to natalizumab, which effectively controlled MS activity, and five years later to fingolimod due to increasing titers of serum JCV antibodies, but later on developed insidious worsening of physical and cognitive disability (EDSS 5.5), suggestive of secondary progressive MS, as well as epilepsy. She had no personal or family history of migraine, stroke ou psychiatric conditions. At age 62 years, no-cost testing for genetic leukoencephalopathies became available for our site and revealed one likely pathogenic variant in NOTCH3, the gene associated with autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In retrospect, her MRI scans were assessed as compatible not only with MS but also with CADASIL, due to involvement of the external capsule and temporal lobes bilaterally. Genetic counseling was performed, management of vascular risk factors was intensified, and she was kept on fingolimod.

Discussion
CADASIL is a monogenic disease associated with recurrent small-vessel ischaemic strokes, migraine, and dementia. As CADASIL often has a relapsing-remitting presentation and widespread cerebral and brainstem hyperintense white matter lesions, misdiagnosis with MS can occur. However, in this case, features such as gadolinium-enhancing and spinal cord lesions and response to steroids were rather suggestive of MS. We found similar cases in the literature, indicating that the association between MS and CADASIL may be more than casual.

Final Commentaries
Our case highlights that CADASIL may mimic or coexist with MS, yet the relationship between these conditions is yet to be determined. Genetic testing for leukoencephalopathies may prove useful for selected patients with MS.

Palavras Chave

CADASIL; NOTCH3; Multiple Sclerosis; Leukoencephalopathy; Autoimmune Diseases.