AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

The Priority Structure of Bank Regulatory Capital: The Case of Subordinated Debt

The aftermath of a crisis often brings reflections on the adequacy of regulatory capital against financial shocks. Accordingly, succeeding regulatory interventions focus on strengthening the resilience of the banking system by improving the quality and quantity of capital, and subordinated debt (sub-debt) remains key to these reforms. Whether, however, the regulatory motive underpins the decision of banks to issue sub-debt is unclear. Moreover, the perceptions of shareholders on the regulatory function of sub-debt are less understood. This thesis attempts to answer these questions by first reviewing other roles of sub-debt then testing if regulation drives its issuance and finally revealing shareholder incentives that weaken its regulatory function. Contrasting capital requirement motives with other explanations, and accounting for equity issuance, we find that banks issue sub-debt primarily to improve their regulatory capital buffer. While a few non-regulatory factors, related to easier entry conditions to debt market, influence the issuance decision, their economic impact is smaller than the impact of the buffer. By exploring how variations in tail risk and size influence the sub-debt and equity issuance decisions by banks with low buffers, we show that issuance choices do not reflect risk-shifting incentives. Next, we review shareholders’ perceptions of the regulatory value of sub-debt vis-a-vis the risk-shifting and wealth-expropriation incentives associated with senior debt by comparing the reaction of stocks to these security announcements. We find that senior debt incentives are more valuable than the regulatory benefit of sub-debt. Contrary to regulatory expectations, announcement of sub-debt (capital-improving) offers are valueless even when undertaken by risky or less-capitalized banks; rather, senior debt offered by these vulnerable banks generate significant shareholder value. Pursuant to these risk-shifting motives, senior debt issuers get riskier post-issuance. These findings suggest that the broader debt priority structure harbours perverse incentives that dilute the regulatory effectiveness of sub-debt

Update on Cysticercosis Epileptogenesis: the Role of the Hippocampus.

Neurocysticercosis (NCC) is the most common helminthic infection of the nervous system and a frequent cause of reactive seizures and epilepsy worldwide. In many cases, multiple episodes of focal seizures related to an identifiable parenchymal brain cyst (and likely attributable to local damage) continue for years after the cyst resolves. However, cases where seizure semiology, interictal EEG abnormalities, and parasites location do not correlate raise concerns about the causal relationship between NCC and either reactive seizures or epilepsy, as well as the epileptogenic potential of parasites. Neurosurgical series of patients with intractable epilepsy and cross-sectional population-based studies have shown a robust association between NCC and hippocampal sclerosis (HS), which might contribute to the above-referred inconsistencies. Current information does not allow to define whether in patients with NCC, HS could result from recurrent seizure activity from a local or distant focus or from chronic recurrent inflammation. In either case, HS may become the pathological substrate of subsequent mesial temporal lobe epilepsy (MTLE). Longitudinal clinical- and population-based cohort studies are needed to evaluate the causal relationship between NCC and HS and to characterize this association with the occurrence of MTLE. If a cause-and-effect relationship between NCC and HS is demonstrated, NCC patients could be assessed to examine neuronal mechanisms of hippocampal epileptogenesis in comparison with animal models, to identify biomarkers of hippocampal epileptogenesis, and to develop novel interventions to prevent epilepsy in NCC and perhaps in other forms of acquired epilepsy

Update on Cysticercosis Epileptogenesis: the Role of the Hippocampus.

Neurocysticercosis (NCC) is the most common helminthic infection of the nervous system and a frequent cause of reactive seizures and epilepsy worldwide. In many cases, multiple episodes of focal seizures related to an identifiable parenchymal brain cyst (and likely attributable to local damage) continue for years after the cyst resolves. However, cases where seizure semiology, interictal EEG abnormalities, and parasites location do not correlate raise concerns about the causal relationship between NCC and either reactive seizures or epilepsy, as well as the epileptogenic potential of parasites. Neurosurgical series of patients with intractable epilepsy and cross-sectional population-based studies have shown a robust association between NCC and hippocampal sclerosis (HS), which might contribute to the above-referred inconsistencies. Current information does not allow to define whether in patients with NCC, HS could result from recurrent seizure activity from a local or distant focus or from chronic recurrent inflammation. In either case, HS may become the pathological substrate of subsequent mesial temporal lobe epilepsy (MTLE). Longitudinal clinical- and population-based cohort studies are needed to evaluate the causal relationship between NCC and HS and to characterize this association with the occurrence of MTLE. If a cause-and-effect relationship between NCC and HS is demonstrated, NCC patients could be assessed to examine neuronal mechanisms of hippocampal epileptogenesis in comparison with animal models, to identify biomarkers of hippocampal epileptogenesis, and to develop novel interventions to prevent epilepsy in NCC and perhaps in other forms of acquired epilepsy

Antiseizure Drugs and Movement Disorders

The relationship between antiseizure drugs and movement disorders is complex and not adequately reviewed so far. Antiseizure drugs as a treatment for tremor and other entities such as myoclonus and restless leg syndrome is the most common scenario, although the scientific evidence supporting their use is variable. However, antiseizure drugs also represent a potential cause of iatrogenic movement disorders, with parkinsonism and tremor the most common disorders. Many other antiseizure drug-induced movement disorders are possible and not always correctly identified. This review was conducted by searching for all the possible combinations between 15 movement disorders (excluding ataxia) and 24 antiseizure drugs. The main objective was to describe the movement disorders treated and worsened or induced by antiseizure drugs. We also summarized the proposed mechanisms and risk factors involved in the complex interaction between antiseizure drugs and movement disorders. Antiseizure drugs mainly used to treat movement disorders are clonazepam, gabapentin, lacosamide, levetiracetam, oxcarbazepine, perampanel, phenobarbital, pregabalin, primidone, topiramate, and zonisamide. Antiseizure drugs that worsen or induce movement disorders are cenobamate, ethosuximide, felbamate, lamotrigine, phenytoin, tiagabine, and vigabatrin. Antiseizure drugs with a variable effect on movement disorders are carbamazepine and valproate while no effect on movement disorders has been reported for brivaracetam, eslicarbazepine, lacosamide, and stiripentol. Although little information is available on the adverse effects or benefits on movement disorders of newer antiseizure drugs (such as brivaracetam, cenobamate, eslicarbazepine, lacosamide, and rufinamide), the evidence collected in this review should guide the choice of antiseizure drugs in patients with concomitant epilepsy and movement disorders. Finally, these notions can lead to a better understanding of the mechanisms involved in the pathophysiology and treatments of movement disorders

Correction to: Antiseizure Drugs and Movement Disorders (vol 36, pg 859, 2022)

The relationship between antiseizure drugs and movement disorders is complex and not adequately reviewed so far. Antiseizure drugs as a treatment for tremor and other entities such as myoclonus and restless leg syndrome is the most common scenario, although the scientific evidence supporting their use is variable. However, antiseizure drugs also represent a potential cause of iatrogenic movement disorders, with parkinsonism and tremor the most common disorders. Many other antiseizure drug-induced movement disorders are possible and not always correctly identified. This review was conducted by searching for all the possible combinations between 15 movement disorders (excluding ataxia) and 24 antiseizure drugs. The main objective was to describe the movement disorders treated and worsened or induced by antiseizure drugs. We also summarized the proposed mechanisms and risk factors involved in the complex interaction between antiseizure drugs and movement disorders. Antiseizure drugs mainly used to treat movement disorders are clonazepam, gabapentin, lacosamide, levetiracetam, oxcarbazepine, perampanel, phenobarbital, pregabalin, primidone, topiramate, and zonisamide. Antiseizure drugs that worsen or induce movement disorders are cenobamate, ethosuximide, felbamate, lamotrigine, phenytoin, tiagabine, and vigabatrin. Antiseizure drugs with a variable effect on movement disorders are carbamazepine and valproate while no effect on movement disorders has been reported for brivaracetam, eslicarbazepine, lacosamide, and stiripentol. Although little information is available on the adverse effects or benefits on movement disorders of newer antiseizure drugs (such as brivaracetam, cenobamate, eslicarbazepine, lacosamide, and rufinamide), the evidence collected in this review should guide the choice of antiseizure drugs in patients with concomitant epilepsy and movement disorders. Finally, these notions can lead to a better understanding of the mechanisms involved in the pathophysiology and treatments of movement disorders

Regional variation in brain tissue texture in patients with tonic-clonic seizures.

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) seizures and 53 healthy controls; images were bias-corrected, entropy maps calculated, normalized to a common space, smoothed, and compared between groups (TC patients and controls using ANCOVA; covariates, age and sex; SPM12, family-wise error correction for multiple comparisons, p<0.01). Decreased entropy, indicative of increased tissue homogeneity, appeared in major autonomic (ventromedial prefrontal cortex, hippocampus, dorsal and ventral medulla, deep cerebellar nuclei), motor (sensory and motor cortex), or both motor and autonomic regulatory sites (basal-ganglia, ventral-basal cerebellum), and external surfaces of the pons. The anterior and posterior thalamus and midbrain also showed entropy declines. Only a few isolated regions showed increased entropy. Among the spared autonomic regions was the anterior cingulate and anterior insula; the posterior insula and cingulate were, however, affected. The entropy alterations overlapped areas of tissue changes found earlier with volumetric measures, but were more extensive, and indicate widespread injury to tissue within critical autonomic and breathing regulatory areas, as well as prominent damage to more-rostral sites that exert influences on both breathing and cardiovascular regulation. The entropy measures provide easily-collected supplementary information using only T1-weighted images, showing aspects of tissue integrity other than volume change that are important for assessing function

Regional cortical thickness changes accompanying generalized tonic-clonic seizures.

ObjectiveGeneralized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms.MethodsHigh-resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic-clonic seizures (Mean age ± SD: 37.1 ± 12.6 years, 22 male) at Case Western Reserve University, University College London, and the University of California at Los Angeles. Control data included 530 healthy individuals (37.1 ± 12.6 years; 220 male) from UCLA and two open access databases (OASIS and IXI). Cortical thickness group differences were assessed at all non-cerebellar brain surface locations (P < 0.05 corrected).ResultsIncreased cortical thickness appeared in post-central gyri, insula, and subgenual, anterior, posterior, and isthmus cingulate cortices. Post-central gyri increases were greater in females, while males showed more extensive cingulate increases. Frontal and temporal cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital cortices showed thinning. The extents of thickness changes were sex- and hemisphere-dependent, with only males exhibiting right-sided and posterior cingulate thickening, while females showed only left lateral orbitofrontal thinning. Regional cortical thickness showed modest correlations with seizure frequency, but not epilepsy duration.SignificanceCortical thickening and thinning occur in patients with generalized tonic-clonic seizures, in cardiovascular and somatosensory areas, with extent of changes sex- and hemisphere-dependent. The data show injury in key autonomic and respiratory cortical areas, which may contribute to dysfunctional cardiorespiratory patterns during seizures, as well as to longer-term SUDEP risk