Summary
We convened an international group of experts to standardize definitions of New‐Onset Refractory Status Epilepticus (NORSE), Febrile Infection‐Related Epilepsy Syndrome (FIRES), and related ...conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in‐person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion‐Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super‐refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.
There is significant overlap between knowledge and its clinical application in stroke and thrombosis & vascular medicine. Formal integration of training is, however, not standard. After the ...hyperacute phase of management, personalized medical decisions are often needed regarding antithrombotics and anticoagulants that leverage clinical practice parameters from both disciplines with a unique emphasis on minimizing neurologic treatment complications. We completed an ad hoc survey of adult thrombosis fellowships at several North American centers. We discovered that direct integration of training programs is not prevalent, suggesting a role for more deliberate integration of training programs. We provide a framework and resources for consideration that directly improve, by design, integrated clinical experiences during training, harnessing the strengths in both stroke and thrombosis programs.
New-onset refractory status epilepticus (NORSE) is a clinical presentation where an individual develops refractory status epilepticus without active epilepsy, or related neurological conditions. A ...subset of these individuals has a preceding fever and would be diagnosed with febrile infection-related epilepsy syndrome (FIRES). The underlying etiology of this condition varies and includes autoimmune and viral encephalitides. These conditions require multiple specialized health care teams working collaboratively and specific resources for investigation of the underlying etiology and management to provide optimal patient care. In this paper, we provide: (1) recommendations upon early recognition of NORSE and FIRES, (2) guidance on the resources needed to optimally provide care, and (3) guidance on considerations to initiate transfer of patients to a more specialized medical center. Additional recommendations for resource-austere centers without the ability to transfer such patients are also discussed. These recommendations are only for adult patients with NORSE as pediatric patients may require additional special considerations.
The coronavirus disease 2019 (COVID-19) pandemic has in some regions overwhelmed the capacity and staffing needs of healthcare systems, necessitating the provision of resources and staff from ...different disciplines to aid COVID treatment teams. Stroke centers have multidisciplinary clinical and procedural expertise to support COVID treatment teams. Staff safety and patient safety are essential, as are open lines of communication between stroke center leaders and hospital leadership in a pandemic where policies and procedures can change or evolve rapidly. Support needs to be allocated in a way that allows for the continued operation of a fully capable stroke center, with the ability to adjust if stroke center volume or staff attrition requires.
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
The idiopathic generalized epilepsies encompass a class of epileptic seizure types that ...exhibit a polygenic and heritable etiology. Advances in molecular biology and genetics have implicated defects in certain types of voltage-gated calcium channels and their ancillary subunits as important players in this form of epilepsy. Both T-type and P/Q-type channels appear to mediate important contributions to seizure genesis, modulation of network activity, and genetic seizure susceptibility. Here, we provide a comprehensive overview of the roles of these channels and associated subunits in normal and pathological brain activity within the context of idiopathic generalized epilepsy.
It is well established that misfolded forms of cellular prion protein (PrP PrPC) are crucial in the genesis and progression of transmissible spongiform encephalitis, whereas the function of native ...PrPC remains incompletely understood. To determine the physiological role of PrPC, we examine the neurophysiological properties of hippocampal neurons isolated from PrP-null mice. We show that PrP-null mouse neurons exhibit enhanced and drastically prolonged N-methyl-D-aspartate (NMDA)-evoked currents as a result of a functional upregulation of NMDA receptors (NMDARs) containing NR2D subunits. These effects are phenocopied by RNA interference and are rescued upon the overexpression of exogenous PrPC. The enhanced NMDAR activity results in an increase in neuronal excitability as well as enhanced glutamate excitotoxicity both in vitro and in vivo. Thus, native PrPC mediates an important neuroprotective role by virtue of its ability to inhibit NR2D subunits.
Post-stroke dysphagia is common and associated with significant morbidity and mortality, rendering bedside screening of significant clinical importance. Using voice as a biomarker coupled with deep ...learning has the potential to improve patient access to screening and mitigate the subjectivity associated with detecting voice change, a component of several validated screening protocols.
In this single-center study, we developed a proof-of-concept model for automated dysphagia screening and evaluated the performance of this model on training and testing cohorts. Patients were admitted to a comprehensive stroke center, where primary English speakers could follow commands without significant aphasia and participated on a rolling basis. The primary outcome was classification either as a pass or fail equivalent using a dysphagia screening test as a label. Voice data was recorded from patients who spoke a standardized set of vowels, words, and sentences from the National Institute of Health Stroke Scale. Seventy patients were recruited and 68 were included in the analysis, with 40 in training and 28 in testing cohorts, respectively. Speech from patients was segmented into 1,579 audio clips, from which 6,655 Mel-spectrogram images were computed and used as inputs for deep-learning models (DenseNet and ConvNext, separately and together). Clip-level and participant-level swallowing status predictions were obtained through a voting method.
The models demonstrated clip-level dysphagia screening sensitivity of 71% and specificity of 77% (F1 = 0.73, AUC = 0.80 95% CI: 0.78-0.82). At the participant level, the sensitivity and specificity were 89 and 79%, respectively (F1 = 0.81, AUC = 0.91 95% CI: 0.77-1.05).
This study is the first to demonstrate the feasibility of applying deep learning to classify vocalizations to detect post-stroke dysphagia. Our findings suggest potential for enhancing dysphagia screening in clinical settings. https://github.com/UofTNeurology/masa-open-source.
Summary
Purpose: High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up to ...seizure onset is unknown. Also, recording HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine whether HFOs could be recorded using commercially available depth macroelectrodes. We also examined the spatial distribution and temporal progression of HFOs during the transition to seizure activity.
Methods: Intracranial electroencephalography (EEG) recordings of 19 seizures were obtained from seven patients with temporal lobe epilepsy using commercial depth or subdural electrodes. EEG recordings were analyzed for frequency content in five spectral bands spanning DC‐500 Hz. We examined the spatial distribution of the different spectral bands 5 s before and 5 s after seizure onset. Temporal changes in the spectral bands were studied in the 30‐s period leading up to seizure onset.
Results: Three main observations were made. First, HFOs (100–500 Hz) can be recorded using commercial depth and subdural grid electrodes. Second, HFOs, but not <100 Hz oscillations, were localized to channels of ictal onset (100–200, 400–500 Hz, p < 0.05; 300–400 Hz, p < 0.001). Third, temporal analysis showed increased HFO power for approximately 8 s prior to electrographic onset (p < 0.05).
Conclusions: These results suggest that HFOs can be recorded by depth macroelectrodes. Also, HFOs are localized to the region of primary ictal onset and can exhibit increased power during the transition to seizure. Thus, HFOs likely represent important precursors to seizure initiation.
Background and Purpose The safety and efficacy of tenecteplase in patients with ischemic stroke due to medium vessel occlusion (MeVO) are not well studied. We aimed to compare tenecteplase with ...alteplase in stroke due to MeVO.Methods Patients with baseline M2-middle cerebral artery (MCA), M3/M4-MCA, P2/P3/P4-posterior cerebral artery (PCA), A2/A3/A4-anterior cerebral artery (ACA) occlusions from the Alteplase Compared to Tenecteplase (AcT) trial were included. Primary outcome was the proportion of 90-day modified Rankin Scale (mRS) 0–1. Secondary outcomes were 90-day mRS 0–2, ordinal mRS, mortality, quality of life measures (EuroQol 5-Dimension 5-Level, EuroQol visual analog scale), and symptomatic intracerebral hemorrhage (sICH). Initial and final successful reperfusion were reported in patients undergoing endovascular thrombectomy (EVT).Results Among 1,558 patients with available baseline computed tomography angiography; 455 (29.2%) had MeVO of which 27.5% (125/455) were proximal M2; 16.3% (74/455) were distal M2; 35.2% (160/455) were M3/M4; 7.5% (34/455) were A2/A3/A4; and 13.6% (62/455) were P2/P3/P4 occlusions. EVT was performed in 87/455 (19.1%) patients. mRS 0–1 at 90 days was achieved in 37.9% in the tenecteplase versus 34.7% in the alteplase group (adjusted risk ratio aRR 1.07; 95% confidence interval CI 0.91–1.25). Rates of 90-day mRS 0–2, sICH, and mortality were similar in both groups. No statistical difference was noted in initial successful reperfusion rates (13.0% vs. 7.5%) among the 87 patients who underwent endovascular thrombectomy. However, final successful reperfusion was higher in the tenecteplase group (71.7% vs. 60.0%, aRR 1.29, 95% CI 1.04–1.61).Conclusion Intravenous tenecteplase had comparable safety, functional outcomes and quality of life compared to intravenous alteplase among patients with MeVO. Among those treated with EVT, tenecteplase was associated with higher successful reperfusion rates than alteplase.
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