Sleep physiology in patients with epilepsy: Influence of seizures on rapid eye movement (REM) latency and REM duration.

OBJECTIVE: A well-established bidirectional relationship exists between sleep and epilepsy. Patients with epilepsy tend to have less efficient sleep and shorter rapid eye movement (REM) sleep. Seizures are far more likely to arise from sleep transitions and non-REM sleep compared to REM sleep. Delay in REM onset or reduction in REM duration may have reciprocal interactions with seizure occurrence. Greater insight into the relationship between REM sleep and seizure occurrence is essential to our understanding of circadian patterns and predictability of seizure activity. We assessed a cohort of adults undergoing evaluation of drug-resistant epilepsy to examine whether REM sleep prior to or following seizures is delayed in latency or reduced in quantity. METHODS: We used a spectrogram-guided approach to review the video-electroencephalograms of patients' epilepsy monitoring unit admissions for sleep scoring to determine sleep variables. RESULTS: In our cohort of patients, we found group- and individual-level delay of REM latency and reduced REM duration when patients experienced a seizure before the primary sleep period (PSP) of interest or during the PSP of interest. A significant increase in REM latency and decrease in REM quantity were observed on nights where a seizure occurred within 4 h of sleep onset. No change in REM variables was found when investigating seizures that occurred the day after the PSP of interest. Our study is the first to provide insight about a perisleep period, which we defined as 4-h periods before and after the PSP. SIGNIFICANCE: Our results demonstrate a significant relationship between seizures occurring prior to the PSP, during the PSP, and in the 4-h perisleep period and a delay in REM latency. These findings have implications for developing a biomarker of seizure detection as well as longer term seizure risk monitoring.

Interictal discharges in the human brain are travelling waves arising from an epileptogenic source.

While seizure activity may be electrographically widespread, increasing evidence has suggested that ictal discharges may in fact represent travelling waves propagated from a focal seizure source. Interictal epileptiform discharges (IEDs) are an electrographic manifestation of excessive hypersynchronization of cortical activity that occur between seizures and are considered a marker of potentially epileptogenic tissue. The precise relationship between brain regions demonstrating IEDs and those involved in seizure onset, however, remains poorly understood. Here, we hypothesize that IEDs likewise reflect the receipt of travelling waves propagated from the same regions which give rise to seizures. Forty patients from our institution who underwent invasive monitoring for epilepsy, proceeded to surgery and had at least one year of follow-up were included in our study. Interictal epileptiform discharges were detected using custom software, validated by a clinical epileptologist. We show that IEDs reach electrodes in sequences with a consistent temporal ordering, and this ordering matches the timing of receipt of ictal discharges, suggesting that both types of discharges spread as travelling waves. We use a novel approach for localization of ictal discharges, in which time differences of discharge receipt at nearby electrodes are used to compute source location; similar algorithms have been used in acoustics and geophysics. We find that interictal discharges co-localize with ictal discharges. Moreover, interictal discharges tend to localize to the resection territory in patients with good surgical outcome and outside of the resection territory in patients with poor outcome. The seizure source may originate at, and also travel to, spatially distinct IED foci. Our data provide evidence that interictal discharges may represent travelling waves of pathological activity that are similar to their ictal counterparts, and that both ictal and interictal discharges emerge from common epileptogenic brain regions. Our findings have important clinical implications, as they suggest that seizure source localizations may be derived from interictal discharges, which are much more frequent than seizures.

Blood Pressure Goals and Clinical Outcomes after Successful Endovascular Therapy: A Multicenter Study.

OBJECTIVE: Elevated systolic blood pressure (SBP) after successful revascularization (SR) via endovascular therapy (EVT) is a known predictor of poor outcome. However, the optimal SBP goal following EVT is still unknown. Our objective was to compare functional and safety outcomes between different SBP goals after EVT with SR. METHODS: This international multicenter study included 8 comprehensive stroke centers and patients with anterior circulation large vessel occlusion who were treated with EVT and achieved SR. SR was defined as modified thrombolysis in cerebral ischemia 2b to 3. Patients were divided into 3 groups based on SBP goal in the first 24 hours after EVT. Inverse probability of treatment weighting (IPTW) propensity analysis was used to assess the effect of different SBP goals on clinical outcomes. RESULTS: A total of 1,019 patients were included. On IPTW analysis, the SBP goal of <140mmHg was associated with a higher likelihood of good functional outcome and lower odds of hemicraniectomy compared to SBP goal of <180mmHg. Similarly, SBP goal of <160mmHg was associated with lower odds of mortality compared to SBP goal of <180mmHg. In subgroup analysis including only patients with pre-EVT SBP of ≥140mmHg, an SBP of <140mmHg was associated with a higher likelihood of good functional outcome, lower odds of symptomatic intracranial hemorrhage, and lower odds of requirement for hemicraniectomy compared to SBP goal of <180mmHg. INTERPRETATION: SBP goals of <140 and < 160mmHg following SR with EVT appear to be associated with better clinical outcomes than SBP of <180mmHg. ANN NEUROL 2020;87:830-839.

Blood Pressure and Outcome After Mechanical Thrombectomy With Successful Revascularization.

Background and Purpose- Successful reperfusion can be achieved in more than two-thirds of patients treated with mechanical thrombectomy. Therefore, it is important to understand the effect of blood pressure (BP) on clinical outcomes after successful reperfusion. In this study, we investigated the relationship between BP on admission and during the first 24 hours after successful reperfusion with clinical outcomes. Methods- This was a multicenter study from 10 comprehensive stroke centers. To ensure homogeneity of the studied cohort, we included only patients with anterior circulation who achieved successful recanalization at the end of procedure. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage (sICH), mortality, and hemicraniectomy. Results- A total of 1245 patients were included in the study. Mean age was 69±14 years, and 51% of patients were female. Forty-nine percent of patients had good functional outcome at 90-days, and 4.7% suffered sICH. Admission systolic BP (SBP), mean SBP, maximum SBP, SBP SD, and SBP range were associated with higher risk of sICH. In addition, patients in the higher mean SBP groups had higher rates of sICH. Similar results were found for hemicraniectomy. With respect to functional outcome, mean SBP, maximum SBP, and SBP range were inversely associated with the good outcome (modified Rankin Scale score, 0-2). However, the difference in SBP parameters between the poor and good outcome groups was modest. Conclusions- Higher BP within the first 24 hours after successful mechanical thrombectomy was associated with a higher likelihood of sICH, mortality, and requiring hemicraniectomy.

Cervical Artery Dissection in Patients of African Ancestry.

BACKGROUND AND PURPOSE: The majority of published data in cervical artery dissection (CeAD), a common cause of stroke in young adults, derive from populations of European ancestry (EA), including a recent genome-wide study identifying an association with the rs9349379 polymorphism of the PHACTR1 gene. Little is known about CeAD in individuals of African ancestry (AA) despite robust epidemiological data showing increased risk of stroke at younger ages. We hypothesize that AA patients with CeAD have different epidemiology and clinical profiles compared to those of EA, and a different genetic architecture related to rs9349379 of the PHACTR1 gene. METHODS: We searched a single-center database of CeAD to identify AA and EA patients. We compared differential prevalence of CeAD versus all young stroke between AA and EA patients. We characterized clinical profiles via electronic medical record review. Data include descriptive statistics reported as medians or percentages. We also obtained publicly available allele frequencies of rs9349379 in AA and EA populations. RESULTS: AA patients comprise 7% of CeAD cases and 27% of young stroke cases while EA patients comprise 90% of CeAD cases and 70% of young stroke cases. Prevalence of hypertension, diabetes mellitus, and hyperlipidemia were 74, 30, and 50%, respectively, in AA patients compared to 37, 6, and 25% in EA patients. Allele frequencies for the CeAD risk allele, rs9349379(A), are higher in AA populations compared to EA populations. CONCLUSION: AA patients represent a smaller proportion of CeAD cases compared to young stroke cases at our center. AA patients suffering CeAD have higher prevalence of both vascular risk factors and frequency of the CeAD risk allele compared to EA patients. These findings suggest a complex interplay between traditional vascular risk factors and genetic predisposition underlying CeAD pathogenesis. Further prospective research is needed to clarify these associations and disparities.

F2-isoprostanes as a biomarker of oxidative stress in the mouse bladder.

PURPOSE: We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder. MATERIALS AND METHODS: At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared. RESULTS: F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change. CONCLUSIONS: Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study.

Source Localization of Normal Variants Seen on EEG.

PURPOSE: The EEG is an essential neurological diagnostic tool. EEG abnormalities can guide diagnosis and management of epilepsy. There are also distinctive EEG waveforms that are seen in healthy individuals. It is critical not to misinterpret these as abnormal. To emphasize the importance of these waveforms, we analyzed different normal variants via the source localization technology. METHODS: This is a retrospective analysis of EEGs performed at the Duke University Hospital between June 2014 and Dec 2019. We selected samples of vertex waves, Mu, lambda, POSTS, wickets, and sleep spindles for analysis. EEG were imported to Curry 8 (Compumedics) to calculate the dipole and current density. The averaged head model from the Montreal Neurological Institute database was used for reconstruction. RESULTS: Thirty-four patient EEG samples were selected including five vertex, six Mu, four wicket, seven lambda, five POSTS, and seven spindles. Results from source localization showed that vertex waves are localized in the frontocentral area, whereas spindles in the deep midline central region. Mu were identified in the ipsilateral somatosensory cortex. Lambda and POSTS, on the other hand, had maximum results over the bilateral occipital region and wickets in the ipsilateral temporal lobe. CONCLUSIONS: Our results confirm and expand previous hypotheses. This allows us to speculate on the origin of these normal EEG variants. Although this study is limited by small sample size, lack of high-density EEG, and patient-specific MRI, our analysis provides an easily replicable three-dimensional visualization of these waveforms.

Genetic or Autoimmune: POLG-Related Epilepsy Initially Treated as an Autoimmune Encephalitis, a Case Report.

Hospital neurologists participate at the forefront of managing fulminant acute and subacute onset epilepsy, frequently attributed to autoimmune encephalitis (AE). As the recognition of antibody-mediated AE grows, there is a growing number of patients who are treated as antibody-negative AE. While antibody-negative autoimmune processes should be considered in the setting of acute and subacute onset of fulminant epilepsy, other causes must be considered before subjecting patients to long-term immunomodulatory treatments and other potential therapeutic toxicities. We present the case of a previously healthy young man who presented with new-onset refractory seizures treated with escalating doses of anti-epileptic drugs as well as immunosuppression for presumed autoimmune epilepsy. He developed valproic acid induced hepatotoxicity requiring liver transplantation and was later found to have a POLG mutation. We discuss the presentation of POLG mutations as well as the diagnosis of seronegative autoimmune encephalitis. We highlight the need for a broad differential when evaluating new onset refractory seizures in an otherwise healthy person.

Source Imaging of Triphasic Waves and Other Encephalopathies.

PURPOSE: Triphasic waves (TWs) are defined as high-amplitude positive waveforms with preceding and after-going negative waves, typically seen in medically ill patients. TWs manifest in similar clinical presentations as other EEG encephalopathies; however, electrographically, they appear different. To better understand the difference, the authors used two different source localization software programs to find a reproducible and unique signature for TW. METHODS: EEGs performed at Johns Hopkins Hospital and Duke University Hospital were retrospectively analyzed. EEG samples of TW, Delta, Theta-Delta, and Frontal Intermittent Rhythmic Delta Activity were selected. The authors did source localization via Commercial Curry 8 and open-source Brainstorm software. A minimum of 10 stereotypical waveforms per subject were selected. The authors used the Boundary Element Method for the head model, which was derived from the Montreal Neurological Institute averaged imaging data set. Dipole and current density analyses were performed. RESULTS: Twenty-eight patients were selected (10 TW, 4 Frontal Intermittent Rhythmic Delta Activity, 6 Theta-Delta, and 8 Delta). The findings suggest the activation of anterior frontal and midline structures for TW. Frontal Intermittent Rhythmic Delta Activity had a similar localization but without a moving dipole. In comparison, the Delta and Delta-Theta appeared to have a more diffuse origin. CONCLUSIONS: Source analysis of TW via two different software suggests the anterior midline location of TW with anterior to posterior propagation. These findings correlate with the previous hypotheses of TW origin. Retrospective analysis, low number of recording electrodes, and difficult analysis of slow waves limit the interpretation of these results. Nonetheless, this article opens the prospect of future studies in this field.

Blood pressure reduction and outcome after endovascular therapy with successful reperfusion: a multicenter study.

BACKGROUND: Elevated systolic blood pressure (SBP) after mechanical thrombectomy (MT) correlates with worse outcome. However, the association between SBP reduction (SBPr) and outcome after successful reperfusion with MT is not well established. OBJECTIVE: To investigate the association between SBPr in the first 24 hours after successful reperfusion and the functional and safety outcomes of MT. METHODS: A multicenter retrospective study, which included 10 comprehensive stroke centers, was carried out. Patients with acute ischemic stroke and anterior circulation large vessel occlusions who achieved successful reperfusion via MT were included. SBPr was calculated using the formula 100×([admission SBP-mean SBP]/admission SBP). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 90 days. Safety endpoints included symptomatic intracerebral hemorrhage, mortality, and requirement for hemicraniectomy during admission. A generalized mixed linear model was used to study the association between SBPr and outcomes. RESULTS: A total of 1361 patients were included in the final analysis. SBPr as a continuous variable was inversely associated with poor outcome (OR=0.97; 95% CI 0.95 to 0.98; p<0.001) but not with the safety outcomes. Subanalysis based on reperfusion status showed that SBPr was associated with lower odds of poor outcome only in patients with complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI 3)) but not in patients with incomplete reperfusion (mTICI 2b). When SBPr was divided into categories (<1%, 1%-10%, 11%-20%, >20%), the rate of poor outcome was highest in the first group. CONCLUSION: SBPr in the first 24 hours after successful reperfusion was inversely associated with poor outcome. No association between SBPr and safety outcome was found.