Contribution of altered corticospinal microstructure to gait impairment in children with cerebral palsy

ObjectiveCorticospinal tract (CST) injury may lead to motor disorders in children with Cerebral Palsy (CP). However, the precise underlying mechanisms are still ambiguous. We aimed to characterize the CST structure and function in children with CP and determine their contributions to balance and gait impairments.MethodTwenty-six children with spastic CP participated. Transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) were utilized to characterize CST structure and function. Common clinical measures were used to assess gait speed, endurance and balance, and mobility.ResultsCST structure and function were significantly altered in children with CP. Different abnormal patterns of CST structure were identified as either abnormal appearance of brain hemispheres (Group-1) or semi-normal CST appearance (Group-2). We found significant correlations between the DTI parameters of the more affected CST and gait features only in Group-1.ConclusionCST structure and function are abnormal in children with CP and these abnormalities may contribute to balance and gait impairment in some children with CP.SignificanceOur findings may lead to the development of further investigations on the mechanisms underlying gait impairment in children with CP and on decision-making for more effective rehabilitation.     

Engagement of cortico-cortical and cortico-subcortical networks in a patient with epileptic spasms: An integrated neurophysiological study

ObjectiveWe aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques.MethodsSeventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks.ResultsIctal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain.ConclusionsIn this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient.SignificanceCortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.     

Auditory neurophysiological development in early childhood: A growth curve modeling approach

ObjectiveDuring early childhood, the development of communication skills, such as language and speech perception, relies in part on auditory system maturation. Because auditory behavioral tests engage cognition, mapping auditory maturation in the absence of cognitive influence remains a challenge. Furthermore, longitudinal investigations that capture auditory maturation within and between individuals in this age group are scarce. The goal of this study is to longitudinally measure auditory system maturation in early childhood using an objective approach.MethodsWe collected frequency-following responses (FFR) to speech in 175 children, ages 3–8 years, annually for up to five years. The FFR is an objective measure of sound encoding that predominantly reflects auditory midbrain activity. Eliciting FFRs to speech provides rich details of various aspects of sound processing, namely, neural timing, spectral coding, and response stability. We used growth curve modeling to answer three questions: 1) does sound encoding change across childhood? 2) are there individual differences in sound encoding? and 3) are there individual differences in the development of sound encoding?ResultsSubcortical auditory maturation develops linearly from 3-8 years. With age, FFRs became faster, more robust, and more consistent. Individual differences were evident in each aspect of sound processing, while individual differences in rates of change were observed for spectral coding alone.ConclusionsBy using an objective measure and a longitudinal approach, these results suggest subcortical auditory development continues throughout childhood, and that different facets of auditory processing follow distinct developmental trajectories.SignificanceThe present findings improve our understanding of auditory system development in typically-developing children, opening the door for future investigations of disordered sound processing in clinical populations.     

Bradykinesia in Alzheimer’s disease and its neurophysiological substrates

ObjectiveAlzheimer’s disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer’s disease.MethodsTwenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation.ResultsPatients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer’s disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery.ConclusionThis study provides new information on the pathophysiology of altered voluntary movements in Alzheimer’s disease.SignificanceThe study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer’s disease.     

Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study

ObjectivePatients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment.MethodsPatients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients.ResultsWe enrolled 25 MuSK-MG patients (20 females), aged 16–79 years at the study time, with disease duration ranging 0.6–48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005).ConclusionsCholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease.SignificanceR-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is.     

Altered sensorimotor integration in multiple sclerosis: A combined neurophysiological and functional MRI study

ObjectiveTo explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS).MethodsTo evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol.ResultsPatients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen.ConclusionsAbnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration.SignificanceThe combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.     

MRI-related anxiety can induce slow BOLD oscillations coupled with cardiac oscillations

ObjectiveAlthough about 1–2% of MRI examinations must be aborted due to anxiety, there is little research on how MRI-related anxiety affects BOLD signals in resting states.MethodsWe re-analyzed cardiac beat-to beat interval (RRI) and BOLD signals of 23 healthy fMRI participants in four resting states by calculation of phase-coupling in the 0.07–0.13 Hz band and determination of positive time delays (pTDs; RRI leading neural BOLD oscillations) and negative time delays (nTDs; RRI lagging behind vascular BOLD oscillations). State anxiety of each subject was assigned to either a low anxiety (LA) or a high anxiety (HA, with most participants exhibiting moderate anxiety symptoms) category based on the inside scanner assessed anxiety score.ResultsAlthough anxiety strongly differed between HA and LA categories, no significant difference was found for nTDs. In contrast, pTDs indicating neural BOLD oscillations exhibited a significant cumulation in the high anxiety category.ConclusionsFindings may suggest that vascular BOLD oscillations related to slow cerebral blood circulation are of about similar intensity during low/no and elevated anxiety. In contrast, neural BOLD oscillations, which might be associated with a central rhythm generating mechanism (pacemaker-like activity), appear to be significantly intensified during elevated anxiety.SignificanceThe study provides evidence that fMRI-related anxiety can activate a central rhythm generating mechanism very likely located in the brain stem, associated with slow neural BOLD oscillation.     

Identification of a novel BICRA variant leading to the newly described Coffin–Siris syndrome 12

BackgroundPathogenic heterozygous variants in BICRA have recently been identified in patients with SWI/SNF-related intellectual disability (SSRIDD) – Coffin-Siris syndrome 12. So far, only one article reported SSRIDD associated with pathogenic variants in BICRA.Case presentationThe patient’s phenotype include low birth weight, microcephaly, neurodevelopment delay, visual, gastrointestinal, urinary tract impairment, and craniofacial dysmorphism. Whole exome sequencing revealed a novel pathogenic heterozygous variant in exon 6 of BICRA gene c.535C > T (p.(Gln179*)). Sanger sequencing confirmed de novo origin.ConclusionThe clinical findings confirm and supplement the previous study which showed that pathogenic variant in BICRA is commonly characterized by neurodevelopmental, gastrointestinal, and ophthalmologic symptoms, growth retardation, as well as craniofacial dysmorphism.     

The relationship between gross motor function impairment in cerebral palsy and sleeping issues of children and caregivers

AimTo investigate, among children and adolescents with cerebral palsy (CP), the relationship between impairment of the gross motor function and: (i) child sleep disorders; (ii) the need for nocturnal support; and (iii) the quality of sleep of their caregivers.MethodsFor children, we considered their scores on the gross motor function measure (GMFM-88) and on the sleep disturbance scale for children (SDSC), besides analyzing qualitative features about their sleep. For caregivers, we considered their scores in the Pittsburgh sleep quality index (PSQI).ResultsOur sample was comprised of 87 participants with mean age of 11.4 years old (±3.4). We observed correlations between GMFM-88 and disorders of initiating and maintaining sleep (DIMS) (r = −0.22; p = 0.039), sleep–wake transition disorders (SWTD) (r = 0.26; p = 0.017) and disorders of arousal (DA) (r = 0.23; p = 0.033). Children receiving nocturnal support presented lower scores in the GMFM-88 (p = 0.001) and higher scores in the SDSC (p = 0.029). For the caregivers, we found no correlation between GMFM-88 and PSQI. Nonetheless, their PSQI scores correlated with the SDSC scores (r = 0.24; p = 0.027).ConclusionImpairment of the gross motor function correlated with DIMS and the need for nocturnal support but might not have an impact on the caregivers’ sleep, which in turn correlated with child sleep disorders.     

Neuropathy in sporadic inclusion body myositis: A multi-modality neurophysiological study

ObjectiveSporadic inclusion body myositis (sIBM) has been associated with neuropathy. This study employs nerve excitability studies to re-examine this association and attempt to understand underlying pathophysiological mechanisms.MethodsTwenty patients with sIBM underwent median nerve motor and sensory excitability studies, clinical assessments, conventional nerve conduction testing (NCS) and quantitative thermal threshold studies. These results were compared to established normal controls, or results from a normal cohort of older control individuals.ResultsSeven sIBM patients (35%) demonstrated abnormalities in conventional NCS, with ten patients (50%) demonstrating abnormalities in thermal thresholds. Median nerve motor and sensory excitability differed significantly in sIBM patients when compared to normal controls. None of these neurophysiological markers correlated significantly with clinical markers of sIBM severity.ConclusionA concurrent neuropathy exists in a significant proportion of sIBM patients, with nerve excitability studies revealing changes possibly consistent with axolemmal depolarization or concurrent neuronal adaptation to myopathy. Neuropathy in sIBM does not correlate with muscle disease severity and may reflect a differing tissue response to a common pathogenic factor.SignificanceThis study affirms the presence of a concurrent neuropathy in a large proportion of sIBM patients that appears independent of the severity of myopathy.     

SICI during changing brain states: Differences in methodology can lead to different conclusions

BackgroundShort-latency intracortical inhibition (SICI) is extensively used to probe GABAergic inhibitory mechanisms in M1. Task-related changes in SICI are presumed to reflect changes in the central excitability of GABAergic pathways. Usually, the level of SICI is evaluated using a single intensity of conditioning stimulus so that inhibition can be compared in different brain states.ObjectiveHere, we show that this approach may sometimes be inadequate since distinct conclusions can be drawn if a different CS intensity is used.MethodsWe measured SICI using a range of CS intensities at rest and during a warned simple reaction time task.ConclusionsOur results show that SICI changes that occurred during the task could be either larger or smaller than at rest depending on the intensity of the CS. These findings indicate that careful interpretation of results are needed when a single intensity of CS is used to measure task-related physiological changes.     

Functional magnetic resonance brain imaging of imagined walking to study locomotor function after stroke

ObjectiveImagined walking has yielded insights into normal locomotor control and could improve understanding of neurologic gait dysfunction. This study evaluated brain activation during imagined walking in chronic stroke.MethodsTen persons with stroke and 10 matched controls completed a walking test battery and a magnetic resonance imaging session including imagined walking and knee extension tasks. Brain activations were compared between tasks and groups. Associations between activations and composite gait score were also calculated, while controlling for lesion load.ResultsStroke and worse gait score were each associated with lesser overall brain activation during knee extension but greater overall activation during imagined walking. During imagined walking, the stroke group significantly activated the primary motor cortex lower limb region and cerebellar locomotor region. Better walking function was associated with less activation of these regions and greater activation of medial superior frontal gyrus area 9.ConclusionsCompared with knee extension, imagined walking was less sensitive to stroke-related deficits in brain activation but better at revealing compensatory changes, some of which could be maladaptive.SignificanceThe identified associations for imagined walking suggest potential neural mechanisms of locomotor adaptation after stroke, which could be useful for future intervention development and prognostication.     

Neurophysiology of motor skill learning in chronic stroke

ObjectiveMotor learning is relevant in chronic stroke for acquiring compensatory strategies to motor control deficits. However, the neurophysiological mechanisms underlying motor skill acquisition with the paretic upper limb have received little systematic investigation. The aim of this study was to assess the modulation of corticomotor excitability and intracortical inhibition within ipsilesional primary motor cortex (M1) during motor skill learning.MethodsTen people at the chronic stage after stroke and twelve healthy controls trained on a sequential visuomotor isometric wrist extension task. Skill was quantified before, immediately after, 24 hours and 7 days post-training. Transcranial magnetic stimulation was used to examine corticomotor excitability and short- and long-interval intracortical inhibition (SICI and LICI) pre- and post-training.ResultsThe patient group exhibited successful skill acquisition and retention, although absolute skill level was lower compared with controls. In contrast to controls, patients’ ipsilesional corticomotor excitability was not modulated during skill acquisition, which may be attributed to excessive ipsilesional LICI relative to controls. SICI decreased after training for both patient and control groups.ConclusionsOur findings indicate distinct inhibitory networks within M1 that may be relevant for motor learning after stroke.SignificanceThese findings have potential clinical relevance for neurorehabilitation adjuvants aimed at augmenting the recovery of motor function.     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex

BackgroundAlthough tumor necrosis factor (TNF) inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS.Materials and methodsTo assess whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the developing neocortex of E13.5, P7 and adult TNF knock out (TNF^−/−) mice and wildtype (WT) littermates. We also measured changes in gene and protein expression and monoamine levels in adult WT and TNF^−/− mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, the selective soluble TNF inhibitor XPro1595, or the nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult WT and TNF^−/− mice and mice treated with saline, XPro1595, or etanercept with specific behavioral tasks.ResultsTNF deficiency decreased the number of proliferating cells and microglia and increased the number of neurons. At the same time, TNF deficiency decreased the expression of WNT signaling-related proteins, specifically Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Frizzled receptor 6 (FZD6). In contrast to XPro1595, long-term inhibition of TNF with etanercept in adult C57BL/6 mice decreased the number of BrdU⁺ cells in the granule cell layer of the dentate gyrus. Etanercept, but not XPro1595, also impaired spatial learning and memory in the Barnes maze memory test.ConclusionTNF deficiency impacts the organization of neurogenic zones and alters the cell composition in brain. Long-term inhibition of TNF with the nonselective TNF inhibitor etanercept, but not the soluble TNF inhibitor XPro1595, decreases neurogenesis in the adult mouse hippocampus and impairs learning and memory after two months of treatment.     

Epileptogenic network of focal epilepsies mapped with cortico-cortical evoked potentials

ObjectiveThe goal of this study was to investigate the spatial extent and functional organization of the epileptogenic network through cortico-cortical evoked potentials (CCEPs) in patients being evaluated with intracranial stereoelectroencephalography.MethodsWe retrospectively included 25 patients. We divided the recorded sites into three regions: epileptogenic zone (EZ); propagation zone (PZ); and noninvolved zone (NIZ). The root mean square of the amplitudes was calculated to reconstruct effective connectivity network. We also analyzed the N1/N2 amplitudes to explore the responsiveness influenced by epileptogenicity. Prognostic analysis was performed by comparing intra-region and inter-region connectivity between seizure-free and non-seizure-free groups.ResultsOur results confirmed that stimulation of the EZ caused the strongest responses on other sites within and outside the EZ. Moreover, we found a hierarchical connectivity pattern showing the highest connectivity strength within EZ, and decreasing connectivity gradient from EZ, PZ to NIZ. Prognostic analysis indicated a stronger intra-EZ connection in the seizure-free group.ConclusionThe EZ showed highest excitability and dominantly influenced other regions. Quantitative CCEPs can be useful in mapping epileptic networks and predicting surgical outcome.SignificanceThe generated computational connectivity model may enhance our understanding of epileptogenic networks and provide useful information for surgical planning and prognosis prediction.     

Inter trial coherence of low-frequency oscillations in the course of stroke recovery

ObjectiveThe aim was to find a sensitive method to highlight the remodeling of the brain’s bioelectric activity in post-stroke repair.MethodsFifteen mild upper limb paretic stroke patients and age-matched healthy controls were included. Repeated trials of finger tapping around the 10th and 100th days after stroke onset were recorded with a 128-channel EEG. Power spectra and Inter Trial Coherence (ITC) calculations were synchronized to tappings. ITC was correlated with motor performance.ResultsITC, in low frequency bands, designates the motor related bioelectric activity in channel space in both healthy subjects and patients. Ten days after stroke onset, delta-theta ITC was severely reduced compared to baseline, while three months later ITC reorganized partially over the ipsilesional central-parietal areas reflecting the improvement of motor networks. Decreased ITC in the central-parietal area remained significant compared to controls. Delta band ITC over the dorsolateral-prefrontal cortex correlates with the performance on Nine Hole Peg Test. At post-recovery, non-paretic hand tappings show significantly decreased delta-theta ITC over the supplementary motor area, which reflects network remodeling.ConclusionsInter Trial Coherence is a useful measure of brain reorganization during stroke recovery.SignificanceDelta- theta ITC is a sensitive indicator of impaired motor execution.     

Automated electrical source imaging with scalp EEG to define the insular irritative zone: Comparison with simultaneous intracranial EEG

Objective To evaluate the accuracy of automated interictal low-density electrical source imaging (LD-ESI) to define the insular irritative zone (IZ) by comparing the simultaneous interictal ESI localization with the SEEG interictal activity.Methods Long-term simultaneous scalp electroencephalography (EEG) and stereo-EEG (SEEG) with at least one depth electrode exploring the operculo-insular region(s) were analyzed. Automated interictal ESI was performed on the scalp EEG using standardized low-resolution brain electromagnetic tomography (sLORETA) and individual head models. A two-step analysis was performed: i) sublobar concordance between cluster-based ESI localization and SEEG-based IZ; ii) time-locked ESI-/SEEG analysis. Diagnostic accuracy values were calculated using SEEG as reference standard. Subgroup analysis was carried out, based on the involvement of insular contacts in the seizure onset and patterns of insular interictal activity.Results Thirty patients were included in the study. ESI showed an overall accuracy of 53% (C.I. 29–76%). Sensitivity and specificity were calculated as 53% (C.I. 29–76%), 55% (C.I. 23–83%) respectively. Higher accuracy was found in patients with frequent and dominant interictal insular spikes.Conclusions LD-ESI defines with good accuracy the insular implication in the IZ, which is not possible with classical interictal scalp EEG interpretation.SignificanceAutomated LD-ESI may be a valuable additional tool to characterize the epileptogenic zone in epilepsies with suspected insular involvement.     

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population.Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE.ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors.ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.     

Phase-amplitude coupling of ripple activities during seizure evolution with theta phase

ObjectiveHigh-frequency activities (HFAs) and phase-amplitude coupling (PAC) are key neurophysiological biomarkers for studying human epilepsy. We aimed to clarify and visualize how HFAs are modulated by the phase of low-frequency bands during seizures.MethodsWe used intracranial electrodes to record seizures of focal epilepsy (12 focal-to-bilateral tonic-clonic seizures and three focal-aware seizures in seven patients). The synchronization index, representing PAC, was used to analyze the coupling between the amplitude of ripples (80–250 Hz) and the phase of lower frequencies. We created a video in which the intracranial electrode contacts were scaled linearly to the power changes of ripple.ResultsThe main low frequency band modulating ictal-ripple activities was the θ band (4–8 Hz), and after completion of ictal-ripple burst, δ (1–4 Hz)-ripple PAC occurred. The ripple power increased simultaneously with rhythmic fluctuations from the seizure onset zone, and spread to other regions.ConclusionsRipple activities during seizure evolution were modulated by the θ phase. The PAC phenomenon was visualized as rhythmic fluctuations.SignificanceRipple power associated with seizure evolution increased and spread with fluctuations. The θ oscillations related to the fluctuations might represent the common neurophysiological processing involved in seizure generation.