Frequency band coupling with high-frequency activities during seizures shifts from θ band in tonic phase to δ band in clonic phase

Objective: To clarify variations in the relationship between high-frequency activities (HFAs) and low frequency bands from the tonic to the clonic phase in focal to bilateral tonic-clonic seizures (FBTCS), using phase-amplitude coupling. Methods: This retrospective study enrolled six patients with drug-resistant focal epilepsy who underwent intracranial electrode placement for presurgical invasive electroencephalography at Osaka University Hospital (July 2018–July 2019). We used intracranial electrodes to record seizures in focal epilepsy (11 FBTCS). The magnitude of synchronization index (SIm) and receiver operating characteristic (ROC) analysis were used to analyze the coupling between HFA amplitude (80–250 Hz) and lower frequencies phase. Results: The θ (4–8 Hz)-HFA SIm peaked in the tonic phase, whereas the δ (2–4 Hz)-HFA SIm peaked in the clonic phase. ROC analysis indicated that the δ-HFA SIm discriminated well the clonic from the tonic phase. Conclusions: The main low–frequency band modulating the HFA shifted from the θ band in the tonic phase to the δ band in the clonic phase. Significance: In FBTCS, low-frequency band coupling with HFA amplitude varies temporally. Especially, the δ band is specific to the clonic phase. These results suggest dynamically neurophysiological changes in the thalamus or basal ganglia throughout FBTCS.

Automated Analysis of Risk Factors for Postictal Generalized EEG Suppression

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES.Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We studied videoelectroencephalogram (vEEG) recordings of generalized convulsive seizures (GCS) in a cohort of patients in whom respiratory and vEEG recording were carried out during the evaluation in the epilepsy monitoring unit. A validated automated EEG suppression detection tool was used to determine presence and duration of PGES.Results: We studied 148 GCS in 87 patients. PGES occurred in 106/148 (71.6%) seizures in 70/87 (80.5%) of patients. PGES mean duration was 38.7 ± 23.7 (37; 1–169) seconds. Presence of tonic phase during GCS, including decerebration, decortication and hemi-decerebration, were 8.29 (CI 2.6–26.39, p = 0.0003), 7.17 (CI 1.29–39.76, p = 0.02), and 4.77 (CI 1.25–18.20, p = 0.02) times more likely to have PGES, respectively. In addition, presence of decerebration (p = 0.004) and decortication (p = 0.02), older age (p = 0.009), and hypoxemia duration (p = 0.03) were associated with longer PGES durations.Conclusions: In this study, we confirmed observations made with visual analysis, that presence of tonic phase during GCS, longer hypoxemia, and older age are reliably associated with PGES. We found that of the different types of tonic phase posturing, decerebration has the strongest association with PGES, followed by decortication, followed by hemi-decerebration. This suggests that these factors are likely indicative of seizure severity and may or may not be associated with SUDEP. An automated signal processing tool enables objective metrics, and may resolve apparent ambiguities in the role of PGES in SUDEP and seizure severity studies.

Association of peri-ictal brainstem posturing with seizure severity and breathing compromise in patients with generalized convulsive seizures

ObjectiveTo analyze the association between peri-ictal brainstem posturing semiologies with post-ictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS).MethodsProspective, multicenter analysis of GCS. Ictal brainstem semiology was classified as (1) decerebration: bilateral symmetric tonic arm extension, (2) decortication: bilateral symmetric tonic arm flexion only, (3) hemi-decerebration: unilateral tonic arm extension with contralateral flexion and (4) absence of ictal tonic phase. Post-ictal posturing was also assessed. Respiration was monitored using thoraco-abdominal belts, video and pulse oximetry.ResultsTwo hundred ninety-five seizures (180 patients) were analyzed. Ictal decerebration was observed in 122/295 (41.4%), decortication in 47/295 (15.9%) and hemi-decerebration in 28/295 (9.5%) seizures. Tonic phase was absent in 98/295 (33.2%) seizures. Postictal posturing occurred in 18/295 (6.1%) seizures. PGES risk increased with ictal decerebration (OR 14.79, 95% CI [6.18–35.39], p < 0.001), decortication (OR 11.26, 95% CI [2.96–42.93], p < 0.001), or hemi-decerebration (OR 48.56, 95% CI [6.07–388.78], p < 0.001) Ictal decerebration was associated with longer PGES (p = 0.011). Post-ictal posturing was associated with post-convulsive central apnea (PCCA) (p = 0.004), longer hypoxemia (p < 0.001) and SpO2 recovery (p = 0.035).ConclusionsIctal brainstem semiology is associated with increased PGES risk. Ictal decerebration is associated with longer PGES. Post-ictal posturing is associated with a threefold increased risk of PCCA, longer hypoxemia and SpO2 recovery. Peri-ictal brainstem posturing may be surrogate biomarkers for GCS severity identifiable without in-hospital monitoring.Classification of evidenceThis study provides Class III evidence that peri-ictal brainstem posturing is associated with the GCS with more prolonged PGES and more severe breathing dysfunction.

NR2B-siRNA Mediated by Hydroxyapatite Nanoparticles Relieves for Malin-Induced Pain of Mice

To observe the effect of NR2B-siRNA mediated by hydroxyapatite nanoparticles (HA) on formalin-induced inflammatory pain of mice and the expression of NR2B in spinal cord. To preliminarily investigate the feasibility of HA as siRNA carrier to transfer NR2B-siRNA in vivo. The sequence-specific NR2B-siRNA of mice was designed and synthesized initially. Using HA as a siRNA carrier, green fluorescent protein(GFP)-siRNA as the control, 4 ug of NR2B-siRNA was administered into subarachnoid space of mice via conscious injection. On 7th day after intrathecal injection, formalin test was observed for 1 hour in each group, followed by dissection of lumbar segments of spinal cords immediately for use in immunohistochemical staining of NR2B. The results show that NR2B-siRNA not only significantly abolish the nociceptive response of mice in the tonic phase induced by formalin, but also decrease the amount of cells expressing NR2B protein in spinal cord, while GFP-siRNA mediated by HA don’t produce the same effects, which demonstrates that HA is capable of effectively transfering NR2B-siRNA via intrathecal injection, furthermore, HA/NR2B-siRNA complex can significantly reduce formalin-induced pain of mice, and specificly inhibit NR2B expression in spinal cord of mice.

Active tension adaptation at a shortened arterial muscle length: inhibition by cytochalasin-D

Unlike the static length-tension curve of striated muscle, airway and urinary bladder smooth muscles display a dynamic length-tension curve. Much less is known about the plasticity of the length-tension curve of vascular smooth muscle. The present study demonstrates that there were significant increases of ∼15% in the phasic phase and ∼10% in the tonic phase of a third KCl-induced contraction of a rabbit femoral artery ring relative to the first contraction after a 20% decrease in length from an optimal muscle length ( L0) to 0.8-fold L0. Typically, three repeated contractions were necessary for full length adaptation to occur. The tonic phase of a third KCl-induced contraction was increased by ∼50% after the release of tissues from 1.25-fold to 0.75-fold Lo. The mechanism for this phenomenon did not appear to lie in thick filament regulation because there was no increase in myosin light chain (MLC) phosphorylation to support the increase in tension nor was length adaptation abolished when Ca2+ entry was limited by nifedipine and when Rho kinase (ROCK) was blocked by H-1152. However, length adaptation of both the phasic and tonic phases was abolished when actin polymerization was inhibited through blockade of the plus end of actin by cytochalasin-D. Interestingly, inhibition of actin polymerization when G-actin monomers were sequestered by latrunculin-B increased the phasic phase and had no effect on the tonic phase of contraction during length adaptation. These data suggest that for a given level of cytosolic free Ca2+, active tension in the femoral artery can be sensitized not only by regulation of MLC phosphatase via ROCK and protein kinase C, as has been reported by others, but also by a nonmyosin regulatory mechanism involving actin polymerization. Dysregulation of this form of active tension modulation may provide insight into alterations of large artery stiffness in hypertension.