Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

A case of repeated focal motor seizures as expression of an inflammatory cerebral process with suspected dysimmune etiology.

Autoimmune encephalitis (AE) is a condition of severe brain inflammation with a complex differential diagnosis. The identification of a specific neuronal antibody (NA) is not mandatory to diagnose AE. Moreover, even when a NA is detected, the clinical picture can be inconsequential (i.e., GAD-65) and not disease-specific (i.e., LGI1). Peculiar clinical manifestations and specific alterations of conventional tests as cerebral spinal fluid (CSF) and magnetic resonance imaging (MRI) can be sufficient to confirm the diagnostic suspicion of AE. New-onset seizures may be the first manifestation of AE and require immediate treatment. We report the case of a 19-year-old woman with sudden onset of focal motor seizures with unimpaired awareness, resistant to different intravenous antiseizure medications (ASMs). Ancillary tests (MRI, CSF analysis and electroencephalogram) were pathological and compatible with an autoimmune disorder of the brain. A weak positivity of GluR-3 antibody was detected in low serum dilution along with very high levels of angiotensin-converting enzyme in serum. After administration of high-dose corticosteroids, electro-clinical and neuroradiological pictures progressively normalized. This case report suggests that, even without a definite NA positivity, an inflammatory brain disorder of suspected autoimmune etiology should be considered based on clinical assessment and suggestive ancillary tests.