INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia

Background: Congenital hemiplegia is the most common form of cerebral palsy (CP) accounting for 1 in 1300 live births. These children have limitations in capacity to use the impaired upper limb and bimanual coordination deficits which impact on daily activities and participation in home, school and community life. There are currently two diverse intensive therapy approaches. Traditional therapy has adopted a bimanual approach (BIM training) and recently, constraint induced movement therapy (CIMT) has emerged as a promising unimanual approach. Uncertainty remains about the efficacy of these interventions and characteristics of best responders. This study aims to compare the efficacy of CIMT to BIM training to improve outcomes across the ICF for school children with congenital hemiplegia

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Exercise-induced seizures and lateral asymmetry in patients with temporal lobe epilepsy

Objective: The objective of this case report is to better characterize the clinical features and potential pathophysiological mechanisms of exercise-induced seizures. Methods: We report a case series of ten patients from a tertiary epilepsy center, where a clear history was obtained of physical exercise as a reproducible trigger for seizures. Results: The precipitating type of exercise was quite specific for each patient, and various forms of exercise are described including running, swimming, playing netball, dancing, cycling, weight lifting, and martial arts. The level of physical exertion also correlated with the likelihood of seizure occurrence. All ten patients had temporal lobe abnormalities, with nine of the ten patients having isolated temporal lobe epilepsies, as supported by seizure semiology, EEG recordings, and both structural and functional imaging. Nine of the ten patients had seizures that were lateralized to the left (dominant) hemisphere. Five patients underwent surgical resection, with no successful long-term postoperative outcomes. Conclusions: Exercise may be an underrecognized form of reflex epilepsy, which tended to be refractory to both medical and surgical interventions in our patients. Almost all patients in our cohort had seizures localizing to the left temporal lobe. We discuss potential mechanisms by which exercise may precipitate seizures, and its relevance regarding our understanding of temporal lobe epilepsy and lateralization of seizures. Recognition of, as well as advice regarding avoidance of, known triggers forms an important part of management of these patients

Cortical excitability and neurology: insights into the pathophysiology

Transcranial magnetic stimulation (TMS) is a technique developed to non-invasively investigate the integrity of human motor corticospinal tracts. Over the last three decades, the use of stimulation paradigms including single-pulse TMS, paired-pulse TMS, repetitive TMS, and integration with EEG and functional imaging have been developed to facilitate measurement of cortical excitability. Through the use of these protocols, TMS has evolved into an excellent tool for measuring cortical excitability. TMS has high sensitivity in detecting subtle changes in cortical excitability, and therefore it is also a good measure of disturbances associated with brain disorders. In this review, we appraise the current literature on cortical excitability studies using TMS in neurological disorders. We begin with a brief overview of current TMS measures and then show how these have added to our understanding of the underlying mechanisms of brain disorders

Defective interhemispheric inhibition in drug-treated focal epilepsies

Focal epilepsies (FEs) arise from a lateralized network, while in generalized epilepsies (GEs) there is a bilateral involvement from the outset. Intuitively, the corpus callosum is the anatomical substrate for interhemispheric spread

Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state

Abstract Background Mesenchymal stem cells (MSCs) play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs). Methods The effect of soluble factors secreted from MCF7, Hela, and HepG2 cancer cell lines on BM-MSCs was assessed using a Transwell indirect coculture system. After 5 days of coculture, BM-MSCs were characterized by flow cytometry for surface marker expression, by qPCR for gene expression profile, and by confocal immunofluorescence for marker expression. We then measured the sensitivity of cocultured BM-MSCs to chemotherapeutic agents, their cell cycle profile, and their response to DNA damage. The sphere formation, invasive properties, and in-vivo performance of BM-MSCs after coculture with cancer cells were also measured. Results Indirect coculture of cancer cells and BM-MSCs, without direct cell contact, generated slow cycling, chemoresistant spheroid stem cells that highly expressed markers of pluripotency, cancer cells, and cancer stem cells (CSCs). They also displayed properties of a side population and enhanced sphere formation in culture. Accordingly, these cells were termed cancer-induced stem cells (CiSCs). CiSCs showed a more mesenchymal phenotype that was further augmented upon TGF-β stimulation and demonstrated a high expression of the β-catenin pathway and ALDH1A1. Conclusions These findings demonstrate that MSCs, recruited to the tumor microenvironment in large numbers, may display cellular plasticity, acquire a more stem-like state, and acquire some properties of CSCs upon exposure to cancer cell-secreted factors. These acquired characteristics may contribute to tumor progression, survival, and metastasis. Our findings provide new insights into the interactions between MSCs and cancer cells, with the potential to identify novel molecular targets for cancer therapy

Additional file 1: Figure S1. of Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state

showing in-vitro differentiation of CiSCs, Figure S2. showing xenotransplantation of CiSCs under the kidney capsule of nude mice, Figure S3. showing effect of coculturing BM-MSCs with HDF, and Table S1. presenting sequences of primers used. (PDF 1426 kb

Probing for cortical excitability

This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus via intracranial electroencephalography (iEEG). Stimuli consisted of 100 single bi-phasic pulses, delivered every 10 minutes. Neural excitability is estimated by extracting a feature from the iEEG responses to the stimuli, which we dub the mean phase variance (PV). We show that the mean PV increases with the rate of inter-ictal discharges in one patient. In another patient, we show that the mean PV changes with sleep and an epileptic seizure. The results demonstrate a proof-of-principal for the method to be applied in a seizure anticipation framework

Electrical probing of cortical excitability in patients with epilepsy

Standard methods for seizure prediction involve passive monitoring of intracranial electroencephalography (iEEG) in order to track the 'state' of the brain. This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus. Electrical probing enables feature extraction in a more robust and controlled manner compared to passively tracking features of iEEG signals. The probing stimuli consist of 100 bi-phasic pulses, delivered every 10. min. Features representing neural excitability are estimated from the iEEG responses to the stimuli. These features include the amplitude of the electrically evoked potential, the mean phase variance (univariate), and the phase-locking value (bivariate). In one patient, it is shown how the features vary over time in relation to the sleep-wake cycle and an epileptic seizure. For a second patient, it is demonstrated how the features vary with the rate of interictal discharges. In addition, the spatial pattern of increases and decreases in phase synchrony is explored when comparing periods of low and high interictal discharge rates, or sleep and awake states. The results demonstrate a proof-of-principle for the method to be applied in a seizure anticipation framework