Thrombotic thrombocytopenic purpura (TTP) is a disease that, if untreated, carries a mortality as high as 90%. As such, prompt recognition is paramount. TTP is typically associated with small vessel occlusions, but large vessel occlusions have rarely been reported. We present a case of congenital TTP, known as Upshaw-Shulman syndrome, in a young woman with recurrent TIAs and subsequent left M1 occlusion with left Middle Cerebral Artery syndrome.

A 16-year-old girl presented to our institution with multiple episodes of transient focal neurologic deficits, each associated with a new punctate infarct. Standard workup was unrevealing, and cerebral angiogram confirmed a non-specific vasculopathy.  The patient was diagnosed with primary CNS angiitis by an outside institution, and initiated on cyclophosphamide and prednisone. Despite this treatment, recurrent TIAs continued.  Findings of low serum platelets yielded further workup with reduced ADAMTS13 activity of 6%. Standard treatment with fresh frozen plasma (FFP) was followed unexpectedly by a left M1 occlusion, that was not amenable to mechanical thrombectomy.  Nevertheless, treatment with plasma exchange followed by biweekly serial FFP has led to complete disease remission.

We present a case of adolescent onset recurrent TIAs diagnosed elsewhere as CNS angiitis. As treatments were deemed ineffective, workup revealed antibody-negative reduced ADAMTS13 activity. Genetic testing revealed two heterozygous mutations on separate exons, one representing a pathogenic mutation and one representing a variant of unknown significance. We postulate that the latter is in fact a pathogenic variant and mutations were in trans configuration, allowing for an autosomal recessive disease to manifest pathogenicity. Also known as Upshaw-Shulman syndrome, congenital TTP typically presents in infancy.  Our case is remarkable for the late age of onset, and unexpected large vessel occlusion following standard treatment.  TTP should be a consideration for all cases of pediatric onset stroke.