This narrative review aims to evaluate current literature on Dravet syndrome, integrating significant new findings into the existing knowledge of pathophysiology and disease course, and highlighting emerging treatments. Beyond SCN1A pathogenic variants, recent findings implicate an expanding number of genes and polygenic interactions which may play a role in the pathophysiology of Dravet syndrome. Neuroimmune dysregulation during critical periods of early brain development may be an additional contributing factor. There is increased recognition of neurodevelopmental comorbidities and disease progression over the lifetime, with neurological decline in adulthood suggestive of a possible degenerative process. Emerging and investigational therapies, including gene-modulatory therapies, may provide improvement in seizures and other metrics. Along with an evolving understanding of Dravet syndrome, including its multifactorial disease mechanisms, clinical manifestations beyond seizures, and progression of disease, the advent of novel treatments offers the potential for improved care of patients across the lifespan.
This review summarizes recent evidence on when to start oral anticoagulant therapy following stroke, including both common and rare clinical conundrums. While previous recommendations based on Diener’s rule suggested waiting up to 12 days based on stroke severity and neuroradiological findings, newer data support earlier initiation or resumption of anticoagulation, particularly for mild and moderate ischemic strokes, generally within 4 days. In patients with a history of intracerebral hemorrhage, anticoagulation resumption involves weighing thromboembolic risk against recurrent hemorrhage risk, requiring individualized decisions regarding whether and when anticoagulation should be resumed. Clinical recommendations for post-stroke anticoagulation emphasize early, individualized initiation of direct oral anticoagulants for mild-to-moderate ischemic strokes based on neuroimaging. After intracerebral hemorrhage, anticoagulation is generally restarted within 4 to 8 weeks for atrial fibrillation, with earlier resumption potentially warranted in selected high-thromboembolic-risk patients, particularly those with mechanical heart valves.
Minority stroke survivors experience difficulties in access to rehabilitation due to a combination of systemic factors; lack of understanding of their cultural beliefs by health professionals; their colonial thinking and experiences; and they are underrepresented in social participation research. To address the disparity, this paper discusses how research on social participation of community dwelling minority stroke survivors could embrace decolonization. Decolonization of research in social participation can be achieved when minority stroke survivors are engaged in genuine trust and co-production of knowledge with social science researchers. Improvements in uptake and continuation of social participation are sustained when such reciprocal relationships take place. There is a need for cultural competence and humility amongst healthcare professionals working in stroke rehabilitation with minority stroke survivors.
The neurologic manifestations of selected tick-transmitted infections in North America and Eurasia were reviewed. Both Powassan virus in North America, and Tick-Borne Encephalitis (TBE) virus in Eurasia can cause encephalitis, often with significant neurologic morbidity. Lyme disease, Ehrlichia chaffeensis (the cause of human monocytic ehrlichiosis [HME]), and Borrelia miyamotoi infections can cause meningitis (the third primarily in immunocompromised individuals). Patients with Lyme disease may also develop cranial neuropathy, and/or radiculoneuropathy. Tick-borne infections are being increasingly recognized in North America and Eurasia. While many tick-borne infections can cause headaches, lethargy or other non-specific symptoms, these are generally not evidence of nervous system infection – i.e., neuroinvasive disease. The latter is less common but may occur in infections due to Powassan and TBE viruses, in HME and in Lyme disease. Patients with symptomatic nervous system infection due to Powassan or TBE virus are at high risk of developing significant neurologic impairment and sequelae.
This review critically evaluates evidence on sleep spindles (SP), slow oscillations (SOs), and their coordination in mild-to-moderate Alzheimer’s disease (AD), focusing on their relationships with cognition, AD biomarkers, and their therapeutic potential. Longitudinal studies associate greater SP and/or SO activity with better cognition and favourable amyloid and tau profiles after clinical onset. Spindle and SO coupling may index network integrity. Preserved NREM sleep oscillations are associated with lower orexin concentrations and weaker adverse relationships between orexin and cognitive and neuropsychiatric outcomes. Closed-loop acoustic stimulation and slow-oscillatory transcranial direct-current stimulation can modify SO activity, spindle activity, and coupling, although cognitive and biomarker benefits remain uncertain. Spindle-SO activity, including their temporal coupling, are associated with cognition and AD biomarkers across the disease continuum. Closed-loop acoustic and electrical stimulation can modify these oscillations, but biomarker-characterized trials in MCI and AD are needed to determine whether treatment produces durable cognitive and biomarker benefits.
