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Granovsky Y.,Clinical Neurophysiology Laboratory | Anand P.,Imperial College London | Nakae A.,Osaka University | Nascimento O.,Federal University of Fluminense | And 3 more authors.
Pain | Year: 2016

There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. Contact heat evoked potentials were recorded from 226 subjects (114 females), distributed per age decade between 20 and 79 years. Temperature stimuli were delivered by a thermode (32°C-51°C at a rate of 70°C/s). In phase I of the study, we investigated side-to-side differences and reported the maximum normal side-to-side difference in Aδ CHEP peak latency and amplitude for leg, forearm, and face. In phase II, we obtained normative data for 3 CHEP parameters (N 2 P 2 amplitude, N 2 latency, and P 2 latency), stratified for gender and age decades from face, upper and lower limbs, and overlying cervical and lumbar spine. In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain. © 2016 International Association for the Study of Pain.


Campbell S.,Clinical Neurophysiology Laboratory
Neurodiagnostic Journal | Year: 2013

Differentiating between benign occipital transients and epileptic discharges from the occipital lobes is imperative. Focal occipital spikes and sharp waves are not always associated with benign disorders. The occurrence of occipital spikes and spike and wave complexes depends on the child's age, the maturation of the occipital cortex, and the cortex's connection with other structures (Beaumanoir et al. 1993). Clinical manifestations also evolve as the patient ages. Seizure semiology is due to the maturation of the visual system and its connections. An infant from birth to twelve months of age could experience autonomic symptoms such as pallor and vomiting with possible minor motor movements. Visual symptoms and/or headaches are usually not noticed until between fi ve and seven years of age. These visual phenomena can continue into adulthood. © ASET, Missouri.


Srinivasakumar P.,University of Texas Southwestern Medical Center | Trivedi S.,University of Texas Southwestern Medical Center | Wallendorf M.,Washington University in St. Louis | Rao R.,University of Texas Southwestern Medical Center | And 3 more authors.
Pediatrics | Year: 2015

BACKGROUND: The impact of treating electrographic seizures in hypoxic ischemic encephalopathy (HIE) is unknown. METHODS: Neonates $36 weeks with moderate or severe HIE were randomly assigned to either treatment of electrographic seizures alone (ESG) or treatment of clinical seizures (CSG). Conventional EEG video was monitored in both groups for up to 96 hours. Cumulative electrographic seizure burden (SB) was calculated in seconds and converted to log units for analysis. MRI scans were scored for severity of brain injury. Infants underwent neurodevelopmental evaluation at 18 to 24 months. Statistical analyses were performed by using SAS 9.3 version (SAS Institute, Inc, Cary, NC). RESULTS: Thirty-five of 69 neonates (51%) who were randomly assigned and included in the study developed seizures (15 in ESG and 20 in CSG). Excluding infants with status epilepticus, median SB (interquartile range) in seconds in ESG (n = 10) was lower than in CSG (n = 16) (449 [113-2070] vs 2226 [760-7654]; P =.02). ESG had fewer seizures with shorter time to treatment (P =.04). Twenty-four of 30 (80%) surviving infants with seizures underwent neurodevelopmental evaluation at 18 to 24 months. Increasing SB in the combined cohort was significantly associated with higher brain injury scores (P <03) and lower performance scores across all 3 domains on BSID III (P =.03). CONCLUSIONS: In neonates with HIE, EEG monitoring and treatment of electrographic seizures results in significant reduction in SB. SB is associated with more severe brain injury and significantly lower performance scores across all domains on BSID III. © 2015 by the American Academy of Pediatrics. All rights reserved.


Granovsky Y.,Rambam Medical Center | Granovsky Y.,Clinical Neurophysiology Laboratory | Liem K.S.,University Utrecht | Weissman-Fogel I.,Haifa University | And 4 more authors.
European Journal of Pain (United Kingdom) | Year: 2016

Background 'Virtual lesion' ('VL') is a transient disruption of cortical activity during task performance. It can be induced by single pulses or short trains of transcranial magnetic stimulation (TMS) directed to functionally relevant brain areas. We applied 'VL' methodology of a short train of TMS given on top of experimental tonic pain, expecting to see changes in pain scores. Methods Thirty young healthy subjects (15 women) were assessed with active ('VL') or 'sham' TMS in different sessions, randomly. In each session, 30 sec-long contact heat (47.5 °C, right forearm) was applied stand-alone ('baseline') and with 5 sec-long 10 Hz-TMS over left primary motor cortex (M1) starting at 17 sec of the heat stimulation. Results Pain scores decreased after 'VL' or 'sham' (p < 0.001). Independently of the type of TMS, pain reduction was stronger in women (p = 0.012). A triple Sex x Stimulation type ('VL' or 'sham') x Condition ('baseline' heat pain vs. heat pain with TMS) interaction (p = 0.027) indicated stronger pain reduction by 'VL' in women (p = 0.008) and not in men (p = 0.78) as compared to 'baseline'. Pain catastrophizing and perceived stress ratings affected the model (p = 0.010 and p < 0.001, respectively), but without sex differences. Conclusions This study indicates that interactions between cortical excitability of the motor cortex and nociceptive processing may be gender-related. © 2015 European Pain Federation.


Ambrosini E.,Istituto Superiore di Sanita | Sicca F.,Clinical Neurophysiology Laboratory | Brignone M.S.,Istituto Superiore di Sanita | D'adamo M.C.,University of Perugia | And 19 more authors.
Human Molecular Genetics | Year: 2014

Short QT3 syndrome (SQT3S) is a cardiac disorder characterized by a high risk of mortality and associated with mutations in Kir2.1 (KCNJ2) channels. The molecular mechanisms leading to channel dysfunction, cardiac rhythm disturbances and neurodevelopmental disorders, potentially associated with SQT3S, remain incompletely understood. Here, we report on monozygotic twins displaying a short QT interval on electrocardiogram recordings and autism-epilepsy phenotype. Genetic screening identified a novel KCNJ2 variant in Kir2.1 that (i) enhanced the channel's surface expression and stability at the plasma membrane, (ii) reduced protein ubiquitylation and degradation, (iii) altered protein compartmentalization in lipid rafts by targeting more channels to cholesterol-poor domains and (iv) reduced interactions with caveolin 2. Importantly, our study reveals novel physiological mechanisms concerning wild-type Kir2.1 channel processing by the cell, such as binding to both caveolin 1 and 2, protein degradation through the ubiquitin-proteasome pathway; in addition, it uncovers a potential multifunctional site that controls Kir2.1 surface expression, protein half-life and partitioning to lipid rafts. The reported mechanisms emerge as crucial also for proper astrocyte function, suggesting the need for a neuropsychiatric evaluation in patients with SQT3S and offering new opportunities for disease management. © The Author 2014. Published by Oxford University Press.

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