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This study characterizes role assignments in maximizing a group's winning probability under the influence of the complementarity of group members' efforts in a group contest, in contrast to prize and multiple resource allocations. We use a constant elasticity of substitution effort aggregator function to parameterize the complementarity. While the prize and resource allocation rules depend on the complementarity, the assignment rule does not when multiple roles are assignable to a single group member: All roles are assigned only to the most productive group member. However, when only a single role per group member is assignable, the assignment rule depends on the complementarity: Roles from greater to less importance are assigned to group members in descending order of their productivity under strong complementarity; only the most important role is assigned to the most productive group member and the others have no effect under weak complementarity. [ABSTRACT FROM AUTHOR]

Objective: Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. Methods: This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. Results: A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8–8.9] vs. 4.9 [95% CI = 4.3–5.5] points; p <.001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2–9.3] vs. 6.4 [95% CI = 4.5–8.3] points; p =.008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3–9.2] vs. 5.4 [95% CI = 3.5–7.3] points; p =.004). Multivariate analysis revealed areas under the curve of.843,.825, and.881 for Parameters 1, 2, and 3, respectively. Significance: SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Ictal direct current shifts (icDCs) and ictal high‐frequency oscillations (icHFOs) have been reported as surrogate markers for better surgical outcomes in epilepsy surgery. icDCs have been classified into two types: rapid and slow development. icDCs have been investigated with a time constant of 10 s (TC10s); however, many institutes use electroencephalography with a time constant of 2 s (TC2s). This study aimed to evaluate whether icDCs can be observed adequately with TC2s; moreover, it examined the relationship between the resected core area of icDCs or icHFOs and surgical outcomes, occurrence rate of each type of icDCs, and relationship between each type of icDCs and pathology. Methods: Twenty‐five patients with intractable focal epilepsy were analyzed retrospectively. icDCs and icHFOs were defined according to common metrics. The amplitude of icDCs was defined at >200 μV and even <200 μV. The two electrodes producing the most prominent icDCs and icHFOs were defined as core electrodes. The correlation between the resected core electrode area and degree of seizure control after surgery was analyzed. icDCs were classified into two types based on a peak latency value cutoff of 8.9 s, and the occurrence rates of both patterns were investigated. Results: icDCs (142/147 seizures [96.6%]) and icHFOs (135/147 seizures [91.8%]) occurred in all patients (100%). Compared with the amplitude of icDCs with TC10s reported in previous studies, the amplitude of icDCs with TC2s was attenuated in the current study. A significant positive correlation was observed between the resected core electrode area and degree of seizure control in both icDCs and icHFOs. A rapid development pattern was observed in 202 of 264 electrodes (76.5%). Significance: Similar to icDCs with TC10s, those with TC2s were observed adequately. Furthermore, favorable outcomes are expected using TC2s, which is currently available worldwide. [ABSTRACT FROM AUTHOR]

Objective: Postseizure functional decline is a concern in poststroke epilepsy (PSE). However, data on electroencephalogram (EEG) markers associated with functional decline are scarce. Thus, we investigated whether periodic discharges (PDs) and their specific characteristics are associated with functional decline in patients with PSE. Methods: In this observational study, patients admitted with seizures of PSE and who had scalp EEGs were included. The association between the presence or absence of PDs and postseizure short‐term functional decline lasting 7 days after admission was investigated. In patients with PD, EEG markers were explored for risk stratification of short‐term functional decline, according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. The association between EEG markers and imaging findings and long‐term functional decline at discharge and 6 months after discharge, defined as an increase in the modified Rankin Scale score compared with the baseline, was evaluated. Results: In this study, 307 patients with PSE (median age = 75 years, range = 35–97 years, 64% males; hemorrhagic stroke, 47%) were enrolled. Compared with 247 patients without PDs, 60 patients with PDs were more likely to have short‐term functional decline (12 [20%] vs. 8 [3.2%], p <.001), with an adjusted odds ratio (OR) of 4.26 (95% confidence interval [CI] = 1.44–12.6, p =.009). Patients with superimposed fast‐activity PDs (PDs+F) had significantly more localized (rather than widespread) lesions (87% vs. 58%, p =.003), prolonged hyperperfusion (100% vs. 62%, p =.023), and a significantly higher risk of short‐term functional decline than those with PDs without fast activity (adjusted OR = 22.0, 95% CI = 1.87–259.4, p =.014). Six months after discharge, PDs+F were significantly associated with long‐term functional decline (adjusted OR = 4.21, 95% CI = 1.27–13.88, p =.018). Significance: In PSE, PDs+F are associated with sustained neuronal excitation and hyperperfusion, which may be a predictor of postseizure short‐ and long‐term functional decline. [ABSTRACT FROM AUTHOR]

Background: The clinical diagnostic criteria for benign adult familial myoclonus epilepsy (BAFME) originally included (1) cortical tremor and infrequent generalized seizures, (2) autosomal dominant inheritance, (3) lack of cognitive decline and other neurological symptoms, (4) electrophysiological findings of cortical reflex myoclonus, and (5) lack of clear clinical progression (BAFME criteria‐1). It was revised such that (1) included partial seizures, and (3) and (5) may develop among middle‐aged patients (Revised criteria‐2). The Japanese Ministry of Health, Labor and Welfare proposed their criteria, which included the EEG and MRI findings (MHLW criteria‐3). Recently, high‐frequency oscillations, superimposed on the giant somatosensory evoked potential P25 component (P25‐HFOs), have been found useful as a biomarker for BAFME diagnosis. Aim: We examined the genetic diagnosis of BAFME type 1 and its consistency with the three diagnostic criteria and P25‐HFOs. Methods: Twenty‐four Japanese patients, who underwent BAFME genetic testing, were rated using three independent diagnostic criteria and P25‐HFOs. Results: Twenty‐one patients were genetically diagnosed with BAFME type 1. Nineteen patients fulfilled BAFME‐1 (sensitivity 90%), and 21 fulfilled Revised‐2 and MHLW criteria‐3 (sensitivity 100%). We could evaluate P25‐HFOs in 19 of the 21 gene‐positive patients, and 17 of the 19 patients showed P25‐HFOs. Three patients with negative genetic testing did not meet any of the criteria and had no P25‐HFOs. Conclusions: The three available clinical diagnostic criteria for BAFME were highly concordant with the positive result for genetic testing. [ABSTRACT FROM AUTHOR]

Objective: To assess whether post‐stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case–control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE. Methods: We performed a post‐hoc analysis of the PROgnosis of POST‐Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced >7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient‐echo T2*‐weighted images. A logistic regression model with ridge penalties was tuned using 10‐fold cross‐validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models. Results: The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p < 0.0001). Compared with the existing models, the new models with cSS (SeLECT‐S and CAVE‐S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT‐S and 0.88 [p = 0.001] for CAVE‐S at the testing data). Interpretation: Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357–370 [ABSTRACT FROM AUTHOR]

Objective: Motivated by the challenges raised by diagnosing poststroke epilepsy (PSE), especially in nonmotor onset seizure (non‐MOS), we aimed to investigate the features of non‐MOS, including seizure sequences, patient characteristics, and electrophysiological and imaging findings in PSE. Methods: This observational cohort study enrolled patients with PSE whose seizure onset was witnessed. According to the International League Against Epilepsy (ILAE) 2017 seizure classification, we classified seizure‐onset symptoms into the non‐MOS and MOS groups. We compared the different clinical characteristics between the two groups. Results: Between 2011 and 2018, we enrolled 225 patients with PSE (median age, 75 years), consisting of 97 (43%) with non‐MOS and 128 (57%) with MOS. Overall, 65 (67%) of the patients without MOS had no subsequent convulsions. Multivariable logistic regression analysis showed significant associations of non‐MOS with absence of poststroke hemiparesis (adjusted odds ratio [OR], 1.88; 95% confidence interval [CI], 1.03–3.42), frontal stroke lobe lesions (OR, 2.11; 95% CI, 1.14–3.91), and putaminal stroke lesions (OR, 2.51; 95% CI, 1.22–5.18) as negative indicators. Postictal single‐photon emission computed tomography (SPECT) detected prolonged hyperperfusion in the temporal lobe more frequently in the non‐MOS than in the MOS group (48% vs 31%; p =.02). The detection rate was higher than spikes/sharp waves in scalp electroencephalography, both in the non‐MOS group (72% vs 33%; p <.001) and the MOS group (68% vs 29%; p <.001). Significance: This study provides the clinical features of non‐MOS in patients with PSE. Compared with the patients with MOS, patients with non‐MOS showed less likely subsequent convulsive seizures, highlighting the clinical challenges. Postictal perfusion imaging and negative indicators of the non‐MOS type may help diagnose and stratify PSE. [ABSTRACT FROM AUTHOR]

Objective: To determine whether brain connectivity differs between focal cortical dysplasia (FCD) types I and II. Methods: We compared cortico‐cortical evoked potentials (CCEPs) as measures of effective brain connectivity in 25 FCD patients with drug‐resistant focal epilepsy who underwent intracranial evaluation with stereo‐electroencephalography (SEEG). We analyzed the amplitude and latency of CCEP responses following ictal‐onset single‐pulse electrical stimulation (iSPES). Results: In comparison to FCD type II, patients with type I demonstrated significantly larger responses in the electrodes near the ictal‐onset zone (<50 mm). These findings persisted when controlling for the location of the epileptogenic zone, as noted in patients with temporal lobe epilepsies, as well as controlling for seizure type, as noted in patients with focal to bilateral tonic‐clonic seizures (FBTCS). In type II, the root mean square (RMS) of CCEP responses dropped substantially from the early segment (10–60 ms) to the middle and late segments (60–600 ms). The middle and late CCEP latency segments showed the largest differences between FCD types I and II. Significance: Focal cortical dysplasia type I may have a greater degree of cortical hyperexcitability as compared with FCD type II. In addition, FCD type II displays a more restrictive area of hyperexcitability in both temporal and spatial domains. In patients with FBTCS and type I FCD, the increased amplitudes of RMS in the middle and late CCEP periods appear consistent with the cortico‐thalamo‐cortical network involvement of FBTCS. The notable differences in degree and extent of hyperexcitability may contribute to the different postsurgical seizure outcomes noted between these two pathological substrates. [ABSTRACT FROM AUTHOR]

Background: Benign adult familial myoclonus epilepsy (BAFME) is one of the diseases that cause cortical myoclonus (CM) with giant somatosensory evoked potentials (SEPs). There are no useful diagnostic biomarkers differentiating BAFME from other CM diseases. Objective: To establish reliable biomarkers including high‐frequency oscillations (HFOs) with giant SEPs for the diagnosis of BAFME. Methods: This retrospective case study included 49 consecutive CM patients (16 BAFME and 33 other CM patients) who exhibited giant P25 or N35 SEPs. SEPs were processed by a band‐pass filter of 400–1000 Hz to analyze HFOs. Clinical and SEP findings were compared between (1) BAFME and other CM groups and (2) patients with presence and absence of P25‐HFOs (HFOs superimposed on giant P25). The diagnostic power of each factor for BAFME was calculated. Results: All 16 BAFME patients showed SEP P25‐HFOs with significantly higher occurrence (P < 0.0001) compared with that of other CM groups. The presence of P25‐HFOs significantly correlated with a BAFME diagnosis (P < 0.0001) and high SEP P25 and N35 amplitudes (P = 0.01 and P < 0.0001, respectively). BAFME was reliably diagnosed using P25‐HFOs with high sensitivity (100%), specificity (87.9%), positive predictive value (80%), and negative predictive value (100%), demonstrating its superiority as a diagnostic factor compared to other factors. Conclusions: P25‐HFOs with giant SEPs is a potential biomarker for BAFME diagnosis. P25‐HFOs may reflect cortical hyperexcitability partly due to paroxysmal depolarizing shifts in epileptic neuronal activities and higher degrees of rhythmic tremulousness than those in ordinary CM. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

The pulmonary delivery of locked nucleic acid containing antisense oligonucleotides (LNA-ASOs) is expected to be a novel therapeutic approach for lung diseases. However, there are two concerns to be considered: immune responses, as the lung has a distinct immune mechanism to protect it from inhaled pathogens; and leakage into blood, since the lung is permeable to small molecules. As phagocytic alveolar macrophages reside in the alveolar space, it is hypothesized that inhaled LNA-ASOs effectively accumulate and exert a knockdown (KD) effect on these cells at low doses. Thus, targeting alveolar macrophages by inhaled LNA-ASOs may reduce these risks. To test this hypothesis, LNA-ASOs targeting Scarb1 or Hprt1 were intratracheally administered to mice. We confirmed the remarkable accumulation of intratracheally administered LNA-ASOs in murine alveolar macrophages and found that they exerted a significant and sequence-dependent KD effect. The dose required for KD in alveolar macrophages was lower than that required to induce KD in the whole lung. Furthermore, when a KD effect was observed in alveolar macrophages, no KD effect was observed in the liver or kidney; however, several inflammatory cytokines were increased in the lung. These results suggest the potential application of LNA-ASOs as an inhaled drug specific to alveolar macrophages. However, further studies on the immuno-stimulatory effects of LNA-ASOs will be necessary for the development of novel inhaled therapeutic agents. [ABSTRACT FROM AUTHOR]