We directly assessed mesial temporal activity in two Alzheimer’s disease (AD) patients without a history or EEG evidence of seizures, using intracranial foramen ovale electrodes. We detected clinically silent hippocampal seizures and epileptiform spikes during sleep, a period when both were most likely to interfere with memory consolidation. These index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.
BackgroundClinicians have qualitatively described rhythmic delta activity as a prominent EEG abnormality in individuals with Angelman syndrome, but this phenotype has yet to be rigorously quantified in the clinical population or validated in a preclinical model. Here, we sought to quantitatively measure delta rhythmicity and evaluate its fidelity as a biomarker.MethodsWe quantified delta oscillations in mouse and human using parallel spectral analysis methods and measured regional, state-specific, and developmental changes in delta rhythms in a patient population.ResultsDelta power was broadly increased and more dynamic in both the Angelman syndrome mouse model, relative to wild-type littermates, and in children with Angelman syndrome, relative to age-matched neurotypical controls. Enhanced delta oscillations in children with Angelman syndrome were present during wakefulness and sleep, were generalized across the neocortex, and were more pronounced at earlier ages.ConclusionsDelta rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in both preclinical and clinical settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-017-9195-8) contains supplementary material, which is available to authorized users.
Background
Ictal-interictal continuum (IIC) continuous EEG (cEEG) patterns including periodic discharges and rhythmic delta activity are associated with poor outcome and in the appropriate clinical context, IIC patterns may represent “electroclinical” status epilepticus (SE). To clarify the significance of IIC patterns and their relationship to “electrographic” SE, we investigated FDG-PET imaging as a complementary metabolic biomarker of SE among patients with IIC patterns.
Methods
A single-center prospective clinical database was ascertained for patients undergoing FDG-PET during cEEG. Following MRI-PET co-registration, the maximum standardized uptake value in cortical and subcortical regions was compared to contralateral homologous and cerebellar regions. Consensus cEEG review and clinical rating of etiology and treatment response were performed retrospectively with blinding. Electrographic SE was classified as discrete seizures without interictal recovery or >3-Hz rhythmic IIC patterns. Electroclinical SE was classified as IIC patterns with electrographic and clinical response to anticonvulsants; clonic activity; or persistent post-ictal encephalopathy.
Results
Eighteen hospitalized subjects underwent FDG-PET during contemporaneous IIC patterns attributed to structural lesions (44 %), neuroinflammatory/neuroinfectious disease (39 %), or epilepsy (11 %). FDG-PET hypermetabolism was common (61 %) and predicted electrographic or electroclinical SE (sensitivity 79 % [95 % CI 53–93 %] and specificity 100 % [95 % CI 51–100 %]; p = 0.01). Excluding electrographic SE, hypermetabolism also predicted electroclinical SE (sensitivity 80 % [95 % CI 44–94 %] and specificity 100 % [95 % CI 51–100 %]; p = 0.01).
Conclusions
In hospitalized patients with IIC EEG patterns, FDG-PET hypermetabolism is common and is a candidate metabolic biomarker of electrographic SE or electroclinical SE.
While rare, neurovascular disorders that occur in pregnant or postpartum women are associated with high morbidity and mortality, thus necessitating prompt identification and treatment. The most common symptoms include headache, focal neurological features, and seizures. Factors such as pregnancy-related hypercoagulability and hemodynamic changes put women at risk for neurovascular disorders in the third trimester and early postpartum period. The biggest risk factors for stroke in pregnancy are hypertension and the preeclampsia/eclampsia spectrum. This review outlines the diagnosis and treatment of pregnant and postpartum women with ischemic and hemorrhagic stroke, cerebral venous sinus thrombosis, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. Trial registration: Not applicable.
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