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    Journal of Clinical Neuroscience 12/2014; 21(12). DOI:10.1016/j.jocn.2014.04.029
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    ABSTRACT: Successive attempts at rebranding may be behind at least some of the proliferation of terms we have at our disposal when describing patients with what are now most often referred to as "psychogenic," "conversion," or "somatoform" symptoms. The most popular term in the movement disorder literature, "psychogenic," provides the aetiology of the disorder within the name, indicating that the symptoms are "born of the mind." Here we argue that it is logical to stop using a term that defines the disorder with regard to a poorly defined aetiology that is not supported by current evidence, and, instead, to use a broad term-functional-not as a "polite eponym" but as a term that is freer from such assumptions and does not reinforce dualistic thinking. The main argument for change is not political or even practical, but scientific. © 2013 Movement Disorder Society.
    Movement Disorders 06/2014; 29(7). DOI:10.1002/mds.25562
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    ABSTRACT: Dystonia has historically been considered a disorder of the basal ganglia, however recent clinical and experimental observations promote the hypothesis that the dystonic neuroanatomical network is wider. In particular there is evidence that the cerebellum is a key structure within this network.(1) Eye blink conditioning is a well characterised experimental paradigm that is highly conserved across species and is dependent upon the cerebellum. Previously it has been shown that levels of eye blink conditioning are reduced in cervical and focal hand dystonia, which suggests impaired cerebellar function in these subsets of dystonia.(2) METHOD: In this study we examined eye blink conditioning in 11 patients with genetically confirmed DYT-1 dystonia and five patients with DYT-6 dystonia. 15 healthy age matched controls were also studied. Eye blink conditioning consisted of the pairing of a conditioning stimulus (CS) (salient 2kHz, 400 ms auditory tone via binaural headphones) with a strong unconditioned electrical stimulus (US) (200 µs pulse width, 5×sensory threshold, supraorbital nerve) 400 ms after the conditioning stimulus in order to elicit a blink reflex. After repeated pairings, conditioned responses (consisting of an eye blink starting before the US) are usually seen in healthy subjects. Conditioning consisted of six learning blocks of 11 trials: trials 1-9 were always CS-US pairs, trial 10 was US only and trial 11 was CS only. The main outcome variable was the number of conditioning responses in the final block. In both patient groups eye blink conditioning was observed, but at the group level there was a trend for patients with DYT-1 dystonia to condition less well (Mann-Whitney test, p=.097) compared to patients with DYT-6 dystonia, who conditioned at a comparable amount to aged matched controls. There is now compelling evidence from studies in animal models of dystonia that the cerebellum has a critical role in the pathophysiology of some forms of dystonia. However evidence for cerebellar involvement in humans with the primary form of the disease is less well established. Eye blink conditioning is a unique electrophysiological paradigm in its ability to test associative learning within the cerebellar circuitry. Although the current data do not reveal statistically significant differences between patients with DYT1 and the small group of patients with DYT6 dystonia currently studied, there is an interesting trend towards less conditioning in DYT1 compared with DYT6 mutation carriers, and recruitment of further DYT6 positive patients is ongoing. If confirmed, this trend fits with previous functional imaging and behavioural studies suggesting differences in cerebellar activation patterns during movement in DYT1 and DYT6 dystonia. There may well be important differences in pathophysiology between patients currently grouped within primary dystonia.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. DOI:10.1136/jnnp-2013-306573.159
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    ABSTRACT: We investigated whether clinical improvement observed after deep brain stimulation (DBS) of the globus pallidus internus (GPi) in cervical dystonia (CD) is paralleled by the normalisation of temporal discrimination thresholds (TDTs), a marker of abnormal sensory processing in CD. TDT was tested in 11 patients with CD after they received DBS and was compared with TDT scores from 24 patients with CD and a group of 61 controls. A clear clinical response to GPi-DBS was demonstrated (total Toronto Western Spasmodic Torticollis Rating Scale scores fell from 50 to 18; P < 0.001). In contrast, TDT remained abnormal in the CD-DBS group (P < 0.001) and was not significantly different from the abnormal TDT range observed in CD. Underlying sensory abnormalities in temporal discrimination observed in dystonia do not seem to be corrected by successful GPi-DBS. This adds further data to the ongoing debate regarding which pathophysiological abnormalities observed in dystonia are likely to be causal in the genesis of the disease rather than epiphenomena observed secondary to abnormal motor activity. © 2013 Movement Disorder Society.
    Movement Disorders 11/2013; 28(13). DOI:10.1002/mds.25581
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    ABSTRACT: Vertigo is sometimes experienced in and around MRI scanners. Mechanisms involving stimulation of the vestibular system by movement in magnetic fields or magnetic field spatial gradients have been proposed. However, it was recently shown that vestibular-dependent ocular nystagmus is evoked when stationary in homogenous static magnetic fields. The proposed mechanism involves Lorentz forces acting on endolymph to deflect semicircular canal (SCC) cupulae. To investigate whether vertigo arises from a similar mechanism we recorded qualitative and quantitative aspects of vertigo and 2D eye movements from supine healthy adults (n = 25) deprived of vision while pushed into the 7T static field of an MRI scanner. Exposures were variable and included up to 135s stationary at 7T. Nystagmus was mainly horizontal, persisted during long-exposures with partial decline, and reversed upon withdrawal. The dominant vertiginous perception with the head facing up was rotation in the horizontal plane (85% incidence) with a consistent direction across participants. With the head turned 90 degrees in yaw the perception did not transform into equivalent vertical plane rotation, indicating a context-dependency of the perception. During long exposures, illusory rotation lasted on average 50 s, including 42 s whilst stationary at 7T. Upon withdrawal, perception re-emerged and reversed, lasting on average 30 s. Onset fields for nystagmus and perception were significantly correlated (p<.05). Although perception did not persist as long as nystagmus, this is a known feature of continuous SSC stimulation. These observations, and others in the paper, are compatible with magnetic-field evoked-vertigo and nystagmus sharing a common mechanism. With this interpretation, response decay and reversal upon withdrawal from the field, are due to adaptation to continuous vestibular input. Although the study does not entirely exclude the possibility of mechanisms involving transient vestibular stimulation during movement in and out of the bore, we argue these are less likely.
    PLoS ONE 10/2013; 8(10):e78748. DOI:10.1371/journal.pone.0078748
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    ABSTRACT: The objective of this article, written by executives of the European Association of Young Neurologists and Trainees (EAYNT), is to illustrate the status quo of neurology training in Europe and give an outlook on ongoing efforts and prospects for junior neurologists. The European Union is an economic and political union that currently encompasses 27 member states with more than 500 million inhabitants (or 7.3% of the world population) (interested readers are referred to http://en.wikipedia.org/wiki/European_Union). Countries of the European Union act as a single market with free movement of citizens, goods, services, and finances. As a consequence, a diploma and postgraduate training obtained in one EU country will be automatically recognized by all other EU member states. At the Lisbon European Council in March 2000, the Heads of State or Government signed a treaty that expresses their ambition of making Europe "the most competitive and dynamic knowledge-based economy in the world, capable of sustainable economic growth with more and better jobs and greater social cohesion" (www.en.wikipedia.org/wiki/Lisbon_Strategy). More than 1.6 million physicians in all the different medical specialties are represented by the European Union of Medical Specialists (UEMS). The UEMS was founded in 1958 and the objectives include the study, promotion, and harmonization of the highest level of training of medical specialists, medical practice, and health care within the European Union. The European Board of Neurology (UEMS-EBN; www.uems-neuroboard.org) is in charge of the implementation of the UEMS policy regarding neurology.
    Neurology 10/2013; 81(18):1626-9. DOI:10.1212/WNL.0b013e3182a9f3ed
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    ABSTRACT: Neurons are highly polarised cells. They make contact with their targets through long axons, along which a steady flux of proteins, lipids, nucleic acids and organelles is constantly maintained. This process is crucial to the development and maintenance of the nervous system, as proven by the many neurodegenerative disorders associated with defective axonal transport. Specific pools of endocytic organelles, which travel along the axon towards the cell body, have assumed a growing importance by virtue of their transported signals. These organelles, named signalling endosomes, vehicle growth factors, such as neurotrophins, and their signalling receptors all the way from the axon terminals to the neuronal cell body. Due to the central importance of neurotrophins in neuronal development and survival, significant efforts have gone over the years into the study of long-range neutrophin trafficking and signalling. Recent evidence has pointed to a role of signalling endosomes in the axonal retrograde transport of other morphogenetic and survival factors, increasing their importance even further. In light of these findings, signalling endosomes have shown potential for integration of different growth factors signals and the ability to decode them by differential sorting in the neuronal cell body. In this review we aim to discuss the state of the field regarding the nature and dynamics of signalling endosomes, their signalling capabilities, their energy requirements for axonal transport and last but not least, their importance in health and disease.
    Seminars in Cell and Developmental Biology 10/2013; 27. DOI:10.1016/j.semcdb.2013.10.004
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    ABSTRACT: The transcranial application of weak currents to the human brain has enjoyed a decade of widespread use, providing a simple and powerful tool for non-invasively altering human brain function. However, our understanding of current delivery and its impact upon neural circuitry leaves much to be desired. We argue that the credibility of conclusions drawn with transcranial direct current stimulation (tDCS) is contingent upon realistic explanations of how tDCS works, and that our present understanding of tDCS limits the technique's use to localize function in the human brain. We outline two central issues where progress is required: the localization of currents, and predicting their functional consequence. We encourage experimenters to eschew simplistic explanations of mechanisms of transcranial current stimulation. We suggest the use of individualized current modeling, together with computational neurostimulation to inform mechanistic frameworks in which to interpret the physiological impact of tDCS. We hope that through mechanistically richer descriptions of current flow and action, insight into the biological processes by which transcranial currents influence behavior can be gained, leading to more effective stimulation protocols and empowering conclusions drawn with tDCS.
    Frontiers in Human Neuroscience 10/2013; 7:613. DOI:10.3389/fnhum.2013.00613
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    ABSTRACT: The diagnosis of psychogenic paroxysmal movement disorders (PPMD) can be challenging, in particular their distinction from the primary paroxysmal dyskinesias (PxD) remains difficult. Here we present a large series of 26 PPMD cases, describe their characteristics, contrast them with primary PxD and focus on their distinguishing diagnostic features. Mean age at onset was 38.6 years, i.e. much later than primary PxD. Women were predominantly affected (73%). Most subjects (88.4%) had long attacks, and unlike primary PxD there was a very high within-subject variability for attack phenomenology, duration and frequency. Dystonia was the most common single movement disorder presentation, but 69.2% of the patients had mixed or complex PxD. In 50% of PPMD cases attack triggers could be identified but these were unusual for primary PxD. 42.3% of patients employed unusual strategies to alleviate or stop the attacks. Response to typical medication used for primary PxD was poor. Precipitation of the disorder due to physical or emotional life events and stressors were documented in 57.6% and 65.3% of the cases respectively. Additional interictal psychogenic signs were documented in 34.6% and further medically unexplained somatic symptoms were present in 50% of the cases. 19.2% of patients had a comorbid organic movement disorder and 26.9% had pre-existing psychiatric comorbidities. Although the phenotypic presentation of PPMD can be highly diverse, certain clinical characteristics help in distinguishing this condition from the primary forms of PxD. Recognition is important as multidisciplinary treatment approaches led to significant improvement in most cases.
    Parkinsonism & Related Disorders 09/2013; DOI:10.1016/j.parkreldis.2013.09.012
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    ABSTRACT: Motion-induced blindness (MIB) is a bistable visual phenomenon in which stationary disks surrounded by a moving pattern intermittently disappear from the viewer's awareness. We explored the cortical network that subserves the MIB phenomenon by targeting its constituent parts with disruptive transcranial magnetic stimulation (TMS), in the form of continuous theta burst stimulation (cTBS). Previous neuroimaging and TMS studies have implicated the right posterior parietal cortex (rPPC) in perceptual transitions such as binocular rivalry, while the visual area V5/MT has been suggested to play a key role in MIB. In this study, we found that cTBS applied to the rPPC lengthened the duration of disappearance in MIB, while cTBS applied to V5/MT shortened the duration of disappearance and decreased the frequency of disappearance in MIB. These results demonstrate a causal role for both the rPPC and V5/MT in MIB, and suggest that the rPPC is involved in shifting resources between competing functional areas, while V5/MT processing initiates and maintains MIB.
    Neuropsychologia 09/2013; 51(13). DOI:10.1016/j.neuropsychologia.2013.09.026
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