Stroke and stroke-like episodes as a new clinical manifestation in Glut1 Deficiency Syndrome

Background: Ever since the initial elucidation of glucose transporter-1 deficiency syndrome (Glut1-DS), there has been a notable expansion in the understanding of the phenotype associated with this condition. This expansion has been so profound that it has facilitated the recognition of atypical manifestations of Glut1-DS. In the context of our study, we present findings related to eight patients diagnosed with Glut1-DS, all of whom underwent at least one episode characterized by acute focal neurological deficits. Methods: Engaging in a comprehensive retrospective analysis, we gathered an array of data encompassing clinical, electrophysiological, neuroradiological, and genetic information. Our emphasis was particularly directed towards three well-documented cases. Results: Within the cohort of 42 individuals diagnosed with Glut1-DS, a subset comprising eight participants, spanning an age range from 6 to 38 years, manifested the onset of neurological disturbances characterized by a spectrum of acute symptoms. These symptoms included dysarthria/aphasia, oral dyskinesia, swallowing difficulties, paraesthesia, facial palsy, hemi/monoplegia, vomiting, headache, and behavioral disturbances. Upon the application of magnetic resonance imaging (MRI), notable indicators of venous congestion and hypoperfusion were discerned, while electroencephalography findings exhibited focal contralateral slowing. Additionally, in two cases, MRI unveiled the presence of an ischaemic brain lesion. Half of the cohort, constituting four patients, were actively adhering to a ketogenic diet (KD), with two of them displaying ketonemia levels lower than the conventional standards during the neurological episode. Conclusions: Within the realm of Glut-1 deficiency syndrome, the occurrence of stroke-like episodes emerges as a recurring manifestation, notably prevalent during the phase of early adulthood, with such episodes being documented in 19% of the patients within our cohort. It is imperative to underscore the significance of recognizing stroke mimics as a pivotal characteristic of Glut1-DS, like other paroxysmal disorders. The question that awaits elucidation pertains to whether a ketogenic diet (KD) can serve as a prophylactic measure against the recurrence of these episodes, and if so, what specific threshold of ketosis would be necessary for this preventive capacity. The imperative for further observational studies becomes evident, aiming to validate and establish the correlation between Glut1-DS and the occurrence of ischaemic stroke.