Incidence of First-Episode Status Epilepticus and Risk Factors in Ontario, Canada.

BACKGROUND: Status epilepticus (SE) is a neurological emergency characterized by prolonged seizures. However, the incidence of first-episode SE is unclear, as estimates vary greatly among studies. Additionally, SE risk factors have been insufficiently explored. Therefore, the objectives of this study were to estimate the incidence of first-episode SE in Ontario, Canada, and estimate the associations between potential sociodemographic and health-related risk factors and first-episode SE. METHODS: We conducted a population-based retrospective cohort study using linked health administrative datasets. We included individuals who completed Canada's 2006 Census long-form questionnaire, lived in Ontario, were between 18 and 105, and had no history of SE. A Cox proportional hazards regression model was used to estimate the hazard ratios for SE within three years associated with each potential risk factor. RESULTS: The final sample included 1,301,700 participants, 140 of whom were hospitalized or had an emergency department visit for first-episode SE during follow-up (3.5 per 100,000 person-years). Older age was the only significant sociodemographic SE risk factor (HR = 1.35, 95% CI = 1.33, 1.37), while health-related risk factors included alcohol or drug abuse (HR = 1.05, 95% CI = 1.02, 1.08), brain tumour or cancer (HR = 1.14, 95% CI = 1.12, 1.15), chronic kidney disease (HR = 1.32, 95% CI = 1.29, 1.36), dementia (HR = 1.42, 95% CI = 1.36, 1.48), diabetes (HR = 1.11, 95% CI = 1.09, 1.12), epilepsy or seizures (HR = 1.05, 95% CI = 1.01, 1.09) and stroke (HR = 1.08, 95% CI = 1.05, 1.11). CONCLUSION: The estimated incidence of SE in a sample of Ontario residents was 3.5 per 100,000 person-years. Older age and several comorbid conditions were associated with higher first-episode SE risk.

Predicting neurologic recovery after severe acute brain injury using resting-state networks.

OBJECTIVE: There is a lack of reliable tools used to predict functional recovery in unresponsive patients following a severe brain injury. The objective of the study is to evaluate the prognostic utility of resting-state functional magnetic resonance imaging for predicting good neurologic recovery in unresponsive patients with severe brain injury in the intensive-care unit. METHODS: Each patient underwent a 5.5-min resting-state scan and ten resting-state networks were extracted via independent component analysis. The Glasgow Outcome Scale was used to classify patients into good and poor outcome groups. The Nearest Centroid classifier used each patient's ten resting-state network values to predict best neurologic outcome within 6 months post-injury. RESULTS: Of the 25 patients enrolled (mean age = 43.68, range = [19-69]; GCS ≤ 9; 6 females), 10 had good and 15 had poor outcome. The classifier correctly and confidently predicted 8/10 patients with good and 12/15 patients with poor outcome (mean = 0.793, CI = [0.700, 0.886], Z = 2.843, p = 0.002). The prediction performance was largely determined by three visual (medial: Z = 3.11, p = 0.002; occipital pole: Z = 2.44, p = 0.015; lateral: Z = 2.85, p = 0.004) and the left frontoparietal network (Z = 2.179, p = 0.029). DISCUSSION: Our approach correctly identified good functional outcome with higher sensitivity (80%) than traditional prognostic measures. By revealing preserved networks in the absence of discernible behavioral signs, functional connectivity may aid in the prognostic process and affect the outcome of discussions surrounding withdrawal of life-sustaining measures.

Functional Neuroimaging as an Assessment Tool in Critically Ill Patients.

OBJECTIVE: Little is known about residual cognitive function in the earliest stages of serious brain injury. Functional neuroimaging has yielded valuable diagnostic and prognostic information in chronic disorders of consciousness, such as the vegetative state (also termed unresponsive wakefulness syndrome). The objective of the current study was to determine if functional neuroimaging could be efficacious in the assessment of cognitive function in acute disorders of consciousness, such as coma, where decisions about the withdrawal of life-sustaining therapies are often made. METHODS: A hierarchical functional magnetic resonance imaging (fMRI) approach assessed sound perception, speech perception, language comprehension, and covert command following in 17 critically ill patients admitted to the intensive care unit (ICU). RESULTS: Preserved auditory function was observed in 15 patients (88%), whereas 5 (29%) also had preserved higher-order language comprehension. Notably, one patient could willfully modulate his brain activity when instructed to do so, suggesting a level of covert conscious awareness that was entirely inconsistent with his clinical diagnosis at the time of the scan. Across patients, a positive relationship was also observed between fMRI responsivity and the level of functional recovery, such that patients with the greatest functional recovery had neural responses most similar to those observed in healthy control participants. INTERPRETATION: These results suggest that fMRI may provide important diagnostic and prognostic information beyond standard clinical assessment in acutely unresponsive patients, which may aid discussions surrounding the continuation or removal of life-sustaining therapies during the early post-injury period. ANN NEUROL 2023;93:131-141.

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy.

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest.

Epilepsia partialis continua in relapsing-remitting multiple sclerosis: A possible distinct relapse phenotype.

Epilepsia partialis continua (EPC) is a rare phenomenon in multiple sclerosis (MS). We describe a patient with relapsing-remitting MS and three episodes of EPC, with refractoriness to anti-seizure drugs but corticosteroid-responsiveness. No lesions likely attributable to her episodes of EPC were seen on 1.5 Tesla MRI, which we hypothesize was due to the small volume of presumed cortical/juxtacortical lesions involving the primary motor cortex. The association with relapsing-remitting disease, corticosteroid responsiveness, and dissemination of episodes of EPC in both space and time in our patient suggest that EPC may represent a distinct relapse phenotype in MS.

The Potential Role of fNIRS in Evaluating Levels of Consciousness.

Over the last few decades, neuroimaging techniques have transformed our understanding of the brain and the effect of neurological conditions on brain function. More recently, light-based modalities such as functional near-infrared spectroscopy have gained popularity as tools to study brain function at the bedside. A recent application is to assess residual awareness in patients with disorders of consciousness, as some patients retain awareness albeit lacking all behavioural response to commands. Functional near-infrared spectroscopy can play a vital role in identifying these patients by assessing command-driven brain activity. The goal of this review is to summarise the studies reported on this topic, to discuss the technical and ethical challenges of working with patients with disorders of consciousness, and to outline promising future directions in this field.

Acute Hemorrhagic Encephalitis Related to COVID-19.

PURPOSE OF REVIEW: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most critical public health challenge in recent history. In this report, we present a case of suspected acute hemorrhagic encephalitis with bilateral intracranial hemorrhages associated with coronavirus disease 2019 (COVID-19) infection. RECENT FINDINGS: A 48-year-old female COVID-19-positive patient developed acute changes in her neurologic status. A head CT with CT angiography demonstrated extensive bilateral parietal and occipital intraparenchymal hemorrhage with intraventricular extension and acute hydrocephalus. The patient was treated with an external ventricular drain, and a CSF sample was tested for SARS-CoV-2 but was found to be negative. SUMMARY: The underlying mechanism for developing acute hemorrhagic encephalitis in viral illnesses may be autoimmune in nature and warrants further investigation. The initial neurologic presentation of COVID-19-related hemorrhagic encephalitis is altered level of consciousness, which may prompt further neurologic examination and imaging to exclude this feature.

Stroke risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases.

OBJECTIVES: To investigate the hypothesis that strokes occurring in patients with coronavirus disease 2019 (COVID-19) have distinctive features, we investigated stroke risk, clinical phenotypes, and outcomes in this population. METHODS: We performed a systematic search resulting in 10 studies reporting stroke frequency among patients with COVID-19, which were pooled with 1 unpublished series from Canada. We applied random-effects meta-analyses to estimate the proportion of stroke among COVID-19. We performed an additional systematic search for cases series of stroke in patients with COVID-19 (n = 125), and we pooled these data with 35 unpublished cases from Canada, the United States, and Iran. We analyzed clinical characteristics and in-hospital mortality stratified into age groups (<50, 50-70, >70 years). We applied cluster analyses to identify specific clinical phenotypes and their relationship with death. RESULTS: The proportions of patients with COVID-19 with stroke (1.8%, 95% confidence interval [CI] 0.9%-3.7%) and in-hospital mortality (34.4%, 95% CI 27.2%-42.4%) were exceedingly high. Mortality was 67% lower in patients <50 years of age relative to those >70 years of age (odds ratio [OR] 0.33, 95% CI 0.12-0.94, p = 0.039). Large vessel occlusion was twice as frequent (46.9%) as previously reported and was high across all age groups, even in the absence of risk factors or comorbid conditions. A clinical phenotype characterized by older age, a higher burden of comorbid conditions, and severe COVID-19 respiratory symptoms was associated with the highest in-hospital mortality (58.6%) and a 3 times higher risk of death than the rest of the cohort (OR 3.52, 95% CI 1.53-8.09, p = 0.003). CONCLUSIONS: Stroke is relatively frequent among patients with COVID-19 and has devastating consequences across all ages. The interplay of older age, comorbid conditions, and severity of COVID-19 respiratory symptoms is associated with an extremely elevated mortality.

Cardiac Intensive Care Unit Management of Patients After Cardiac Arrest: Now the Real Work Begins.

Survival with a good quality of life after cardiac arrest continues to be abysmal. Coordinated resuscitative care does not end with the effective return of spontaneous circulation (ROSC)-in fact, quite the contrary is true. Along with identifying and appropriately treating the precipitating cause, various components of the post-cardiac arrest syndrome also require diligent observation and management, including post-cardiac arrest neurologic injury and myocardial dysfunction, systemic ischemia-reperfusion phenomenon with potential consequent multiorgan failure, and the various sequelae of critical illness. There is growing evidence that an early invasive approach to coronary reperfusion with percutaneous coronary intervention, together with active targeted temperature management and optimization of hemodynamic, ventilator, and metabolic parameters, may improve survival and neurologic outcomes in cardiac arrest survivors. Neuroprognostication is complex, as are survivorship issues and long-term rehabilitation. Our paramedics, emergency physicians, and resuscitation specialists are all to be congratulated for ever-increasing success with ROSC… but now the real work begins.

Electroencephalography after a single unprovoked seizure.

Electroencephalography (EEG) is an essential diagnostic tool in the evaluation of seizure disorders. In particular, EEG is used as an additional investigation for a single unprovoked seizure. Epileptiform abnormalities are related to seizure disorders and have been shown to predict recurrent unprovoked seizures (i.e., a clinical definition of epilepsy). Thus, the identification of epileptiform abnormalities after a single unprovoked seizure can inform treatment options. The current review addresses the relationship between EEG abnormalities and seizure recurrence. This review also addresses factors that are found to improve the yield of recording epileptiform abnormalities including timing of EEG relative to the new-onset seizure, use of repeat studies, use of sleep deprivation and prolonged recordings.

Single-session communication with a locked-in patient by functional near-infrared spectroscopy.

There is a growing interest in the possibility of using functional neuroimaging techniques to aid in detecting covert awareness in patients who are thought to be suffering from a disorder of consciousness. Immerging optical techniques such as time-resolved functional near-infrared spectroscopy (TR-fNIRS) are ideal for such applications due to their low-cost, portability, and enhanced sensitivity to brain activity. The aim of this case study was to investigate for the first time the ability of TR-fNIRS to detect command driven motor imagery (MI) activity in a functionally locked-in patient suffering from Guillain-Barré syndrome. In addition, the utility of using TR-fNIRS as a brain-computer interface (BCI) was also assessed by instructing the patient to perform an MI task as affirmation to three questions: (1) confirming his last name, (2) if he was in pain, and (3) if he felt safe. At the time of this study, the patient had regained limited eye movement, which provided an opportunity to accurately validate a BCI after the fNIRS study was completed. Comparing the two sets of responses showed that fNIRS provided the correct answers to all of the questions. These promising results demonstrate for the first time the potential of using an MI paradigm in combination with fNIRS to communicate with functionally locked-in patients without the need for prior training.

Temporal lobe epilepsy after refractory status epilepticus: an illustrative case and review of the literature.

New onset refractory status epilepticus (NORSE) is a relatively newly defined disease entity, where otherwise healthy individuals develop unrelenting seizures that do not respond to conventional anticonvulsant therapy and may require months of therapy with anesthetic drugs. We have described a case of NORSE who subsequently developed mesial temporal lobe sclerosis (MTS) and recurrent temporal lobe seizures. We discuss the possible pathophysiological mechanisms by which refractory seizures may contribute to the development of temporal lobe epilepsy (TLE).

Deliberate utilization of interaction torques brakes elbow extension in a fast throwing motion.

We tested the hypothesis that in fast arm movements the CNS deliberately utilizes interaction torques to decelerate (brake) joint rotations. Twelve subjects performed fast 2-D overarm throws in which large elbow extension velocities occurred. Joint motions were computed from recordings made with search coils; joint torques were calculated using inverse dynamics. After ball release, a large follow-through shoulder extension acceleration occurred that was initiated by shoulder extensor muscle torque. This shoulder acceleration produced a flexor interaction torque at the elbow that initiated elbow deceleration (braking). An instantaneous mechanical interaction of passive torques then occurred between elbow and shoulder, i.e., elbow extension deceleration produced a large shoulder extensor interaction torque that contributed to the shoulder extension acceleration which, simultaneously, produced a large elbow flexor interaction torque that contributed to elbow extension deceleration, and so on. Late elbow flexor muscle torque also contributed to elbow deceleration. The interaction of passive torques between shoulder and elbow was braked by shoulder flexor muscle torque. In this mechanism, shoulder musculature contributed to braking elbow extension in two ways: shoulder extensors initiated the mechanical interaction of passive torques between shoulder and elbow and shoulder flexors dissipated kinetic energy from elbow braking. It is concluded that, in fast 2-D throws, the CNS deliberately utilizes powerful interaction torques between shoulder and elbow to brake motion at the elbow.

Wrist muscle activation, interaction torque and mechanical properties in unskilled throws of different speeds.

An unexpected property of unskilled overarm throws is that wrist flexion velocity at ball release does not increase in throws of increasing speed. We investigated the nature of the interaction torques and wrist mechanical properties that have been proposed to produce this property. Twelve recreational throwers made seated 2-D throws, which were used as a model for unskilled throwing. Joint motions were computed from recordings made with search coils; joint torques were calculated from inverse dynamics. Wrist flexion velocity at ball release was actually smaller in fast throws than in slow throws. This was associated in fast throws with the decrease in a large wrist flexor muscle torque (i.e., a calculated residual torque) in the last 40 ms before ball release, and its reversal to an extensor torque. Consequently, wrist flexor muscle torque was unable to oppose a small maintained wrist extensor interaction torque that arose from continuing elbow extension acceleration. The decrease in wrist flexor muscle torque was not associated with a decrease in wrist flexor EMG activity, nor with an increase in wrist extensor EMG activity. These findings support the hypothesis that the smaller wrist flexion velocity at ball release in fast 2-D throws results from a wrist extensor interaction torque and from a large wrist extensor viscoelastic torque. We propose that in fast 3-D throws skilled subjects decelerate elbow extension before ball release to help overcome these wrist extensor torques.