Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).

Abbreviations

CIs

confidence intervals

ctDNA

circulating tumor DNA

ddPCR

droplet digital PCR

EGFR

epidermal growth factor receptor

MFs

mutant fractions

NGS

next‐generation sequencing

NSCLC

non‐small cell lung cancer

ORR

overall response rate

OS

overall survival

PD

progressive disease

PFS

progression‐free survival

PR

partial response

SD

stable disease

TKI

tyrosine kinase inhibitor

     

Prospective observational study: Fast ripple localization delineates the epileptogenic zone

ObjectiveTo investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom.MethodsInterictal fast ripples (FRs: 250–500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI.ResultsInterictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43).ConclusionsProspective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones.SignificanceTopological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.     

Delays in the reading and spelling of children with cerebral palsy: Associations with phonological and visual processes

BackgroundThis investigation addresses the question of whether there exists a significant discrepancy in the cognitive abilities of children with cerebral palsy (CP) who, despite the presence of age appropriate communication and language, have reading and spelling delays.AimsWe wanted to discover whether there was a relationship between the phonological and visual perceptual abilities of children with CP and their progress in reading and spelling.Methods and proceduresFifteen children with CP (aged between 6:9 years and 11:6 years) were assessed on reading and spelling; communication and language; non-verbal reasoning; phonological processing; and visual perception.Outcomes and resultsTen of the children had very weak reading and spelling skills. Five children had (mostly) age appropriate scores of reading and spelling. No differences were found between these two groups in non-verbal reasoning or communication and language. However, phonological abilities, visual sequential memory and perception of visuospatial relationships were found to be related to reading and spelling.Conclusions and implicationsThe findings suggest that children with CP are at risk for reading and spelling delays when they have poor phonological processing, visual sequential memory and perception of visuospatial relationships. The implications of the findings for classroom practice are discussed.     

Routine Laboratory Testing Every 4 Versus Every 6 Weeks for Patients on Maintenance Hemodialysis: A Quality Improvement Project

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超声多探头检查在新生儿颅脑疾病诊断中的应用

目的研究超声低频探头和低频探头联合高频探头检查在新生儿颅脑疾病诊断中的准确率和敏感性。 方法选取河源市妇幼保健院自2017年1月至2018年12月收治的有颅脑疾病高危因素(早产、低体质量、多胎妊娠、出生过程有缺氧窒息及产时感染)的新生儿90例作为研究对象。采用随机数字表法将所有新生儿平均分为2组，研究组（45例）给予低频探头联合高频探头进行探查，对照组（45例）仅给予低频探头进行探查。结合CT检查结果和临床治疗，比较2种检测方法的准确率和敏感性。 结果研究组检测新生儿缺氧缺血性脑病、脑室内出血和室管膜下出血诊断准确率分别为87.5%、100%、100%，高于相应对照组（15.38%、12.5%、0%），差异有统计学意义（P<0.05）；研究组和对照组检测脑实质内出血和脑积水的诊断准确率分别为87.5%、100%以及42.85%、66.67%，差异无统计学意义（P>0.05）。研究组检测新生儿颅脑疾病的效率为82.22%，高于对照组（22.22%），差异具有统计学意义（P<0.05）。 结论使用超声低频探头联合高频探头的方法提高了缺氧缺血性脑病、脑室内出血、室管膜下出血等新生儿颅脑疾病诊断的准确率，在诊断新生儿脑实质内出血和脑积水的准确率没有差异，且对颅脑疾病诊断的敏感性较高，因此具有较为重要的临床意义。     

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.     

Alteration of testicular regulatory and functional molecules following long‐time exposure to 900 MHz RFW emitted from BTS

The aim of this investigation was to evaluate changes in testosterone and some of the functional and regulatory molecules of testis such as P450scc, steroidogenic acute regulatory protein (StAR), tumour necrosis factor‐α (TNF‐α), interleukin‐1α (IL‐1α), interleukin‐1β (IL‐1β) and nerve growth factor (NGF) following exposure to 900 MHz radio frequency (RF). Thirty adult male Sprague Dawley rats (190 ± 20 g BW) were randomly classified in three equal groups, control (sham, without any exposure), short‐time exposure (2 hr) (STE) and long‐time exposure (4 hr) (LTE). The exposure was performed for 30 consecutive days. The testosterone level in both exposed groups was significantly less than control (p < .05). Level of TNF‐α in both exposed groups was significantly greater than control (p < .05). IL‐1α and NGF levels in LTE were significantly higher than the STE and control groups (p < .05). Level of IL‐1β in LTE was significantly higher than control (p < .05). Expression of both P450scc and StAR mRNA was significantly down‐regulated in both exposed groups compared to control (p < .05). Our results showed that RFW can affect testis and reproductive function through changes in factors, which are important during steroidogenesis, and also through changes in inflammatory factors, which regulate Leydig cell functions.