Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

An estimated 30% of individuals with autism spectrum disorders (ASD) remain minimally verbal into late childhood, but research on cognition and brain function in ASD focuses almost exclusively on those with good or only moderately impaired language. Here we present a case study investigating auditory processing of GM, a nonverbal child with ASD and cerebral palsy. At the age of 8 years, GM was tested using magnetoencephalography (MEG) whilst passively listening to speech sounds and complex tones. Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech, particularly in the 65–165 ms (M50/M100) time window post-stimulus onset. GM was retested aged 10 years using electroencephalography (EEG) whilst passively listening to pure tone stimuli. Consistent with her MEG response to complex tones, GM showed an unusually early and strong response to pure tones in her EEG responses. The consistency of the MEG and EEG data in this single case study demonstrate both the potential and the feasibility of these methods in the study of minimally verbal children with ASD. Further research is required to determine whether GM's atypical auditory responses are characteristic of other minimally verbal children with ASD or of other individuals with cerebral palsy.

Quantification of white matter abnormalities in neurodegenerative disease

Degeneration of white matter fibre tracts occurs in several neurodegenerative disorders and results in various histological abnormalities including loss of axons, vacuolation, gliosis, axonal varicosities and spheroids, corpora amylacea, extracellular protein deposits, and glial inclusions (GI). This chapter describes quantitative studies that have been carried out on white matter pathology in a variety of neurodegenerative disease. First, in Alzheimer’s disease (AD), axonal loss quantified in histological sections stained with toluidine blue, occurs in several white matter fibre tracts including the optic nerve, olfactory tract, and corpus callosum. Second, in Creutzfeldt-Jakob disease (CJD), sections of cerebral cortex stained with haematoxylin and eosin (H/E) or immunolabelled with antibodies against the disease form of prion protein (PrPsc), reveal extensive vacuolation, gliosis of white matter, and deposition of PrPsc deposits. Third, GI immunolabelled with antibodies against various pathological proteins including tau, -synuclein, TDP-43, and FUS, have been recorded in white matter of a number of disorders including frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and neuronal intermediate filament inclusion disease (NIFID). Axonal varicosities have also been observed in NIFID. There are two important questions regarding white matter pathology that need further investigation: (1) what is the relative importance of white and gray matter pathologies in different disorders and (2) do white matter abnormalities precede or are they the consequence of gray matter pathology?

Acute Exposure to Terrestrial Trunked Radio (TETRA) has effects on the electroencephalogram and electrocardiogram, consistent with vagal nerve stimulation

BACKGROUND: Terrestrial Trunked Radio (TETRA) is a telecommunications system widely used by police and emergency services around the world. The Stewart Report on mobile telephony and health raised questions about possible health effects associated with TETRA signals. This study investigates possible effects of TETRA signals on the electroencephalogram and electrocardiogram in human volunteers. METHODS: Blinded randomized provocation study with a standardized TETRA signal or sham exposure. In the first of two experiments, police officers had a TETRA set placed first against the left temple and then the upper-left quadrant of the chest and the electroencephalogram was recorded during rest and active cognitive processing. In the second experiment, volunteers were subject to chest exposure of TETRA whilst their electroencephalogram and heart rate variability derived from the electrocardiogram were recorded. RESULTS: In the first experiment, we found that exposure to TETRA had consistent neurophysiological effects on the electroencephalogram, but only during chest exposure, in a pattern suggestive of vagal nerve stimulation. In the second experiment, we observed changes in heart rate variability during exposure to TETRA but the electroencephalogram effects were not replicated. CONCLUSIONS: Observed effects of exposure to TETRA signals on the electroencephalogram (first experiment) and electrocardiogram are consistent with vagal nerve stimulation in the chest by TETRA. However given the small effect on heart rate variability and the lack of consistency on the electroencephalogram, it seems unlikely that this will have a significant impact on health. Long-term monitoring of the health of the police force in relation to TETRA use is on-going.

Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems. © 2010 Elsevier Inc.

Novel Virtual Environment for Alternative Treatment of Children with Cerebral Palsy

Cerebral palsy is a severe condition usually caused by decreased brain oxygenation during pregnancy, at birth or soon after birth. Conventional treatments for cerebral palsy are often tiresome and expensive, leading patients to quit treatment. In this paper, we describe a virtual environment for patients to engage in a playful therapeutic game for neuropsychomotor rehabilitation, based on the experience of the occupational therapy program of the Nucleus for Integrated Medical Assistance (NAMI) at the University of Fortaleza, Brazil. Integration between patient and virtual environment occurs through the hand motion sensor “Leap Motion,” plus the electroencephalographic sensor “MindWave,” responsible for measuring attention levels during task execution. To evaluate the virtual environment, eight clinical experts on cerebral palsy were subjected to a questionnaire regarding the potential of the experimental virtual environment to promote cognitive and motor rehabilitation, as well as the potential of the treatment to enhance risks and/or negatively influence the patient’s development. Based on the very positive appraisal of the experts, we propose that the experimental virtual environment is a promising alternative tool for the rehabilitation of children with cerebral palsy.

Efetividade das correntes TENS (Transcutaneous Electrical Nerve Stimulation) na promoção do processo de cicatrização de feridas crónicas: revisão sistemática

Introdução: As feridas crónicas têm um impacto bastante significativo em várias componentes, tais como a física, psicológica e financeira. Estudos efetuados no âmbito da estimulação elétrica (EE) na cicatrização de feridas crónicas mostraram que as correntes bidirecionais, como o TENS (transcutaneous electrical nerve stimulation), parecem ser promissoras. Objetivo: Descrever analiticamente os efeitos das correntes TENS na promoção da cicatrização de feridas crónicas. Métodos: O estudo que efetuámos trata-se de uma revisão sistemática. As bases de dados utilizadas foram: MEDLINE/PubMed, Cochrane Central Register of Controlled Trials, B-on, PEDro. Foram incluídos estudos realizados em humanos com idades superiores ou iguais a 18 anos, podendo ser randomizados ou não. Estes estudos deviam de ter como outcome a taxa de cicatrização. A qualidade dos artigos foi avaliada pela escala PEDro. Resultados: Dos 2505 artigos encontrados, incluímos 14 estudos (7 randomizados e 7 não-randomizados). Destes estudos, 5 focam-se nas feridas diabéticas, 3 incidem nas úlceras de pressão, 1 inclui úlceras venosas e 5 englobam mais do que um tipo de feridas crónicas. A média de idades em todos os estudos varia de 31,1 e 73,1 anos, sendo que o número da amostra varia de 20 a 214 indivíduos. Todos os artigos apresentaram resultados positivos na taxa de cicatrização aquando da aplicação das correntes TENS em qualquer tipo de feridas crónicas. O estudo apresenta algumas limitações na qualidade metodológica e no processo de seleção dos ensaios. Conclusão: A terapia TENS parece ser uma modalidade terapêutica efetiva na promoção do processo de cicatrização de feridas crónicas.

Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study.

BACKGROUND: Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. METHODS: The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison-corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. RESULTS: The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher-transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). CONCLUSIONS: This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB.

Nerve localization techniques for peripheral nerve block and possible future directions

Ultrasound guidance is now a standard nerve localization technique for peripheral nerve block (PNB). Ultrasonography allows simultaneous visualization of the target nerve, needle, local anesthetic injectate and surrounding anatomical structures. Accurate deposition of local anesthetic next to the nerve is essential to the success of the nerve block procedure. Unfortunately, due to limitations in the visibility of both needle tip and nerve surface, the precise relationship between needle tip and target nerve is unknown at the moment of injection. Importantly, nerve injury may result both from an inappropriately placed needle tip and inappropriately placed local anesthetic. The relationship between the block needle tip and target nerve is of paramount importance to the safe conduct of peripheral nerve block. This review summarizes the evolution of nerve localization in regional anesthesia, characterizes a problem faced by clinicians in performing ultrasound guided nerve block and explores the potential technological solutions to this problem.