134 research outputs found
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KIF1C Variants Are Associated with Hypomyelination, Ataxia, Tremor, and Dystonia in Fraternal Twins
Background: KIF1C (Kinesin Family Member 1C) variants have been associated with hereditary spastic paraplegia and spastic ataxia.
Case report: We report fraternal twins presenting with cerebellar ataxia and dystonic tremor. Their brain MRI showed a hypomyelinating leukoencephalopathy. Whole exome sequencing identified a homozygous KIF1C variant in both patients.
Discussion: KIF1C variants can manifest as a complex movement disorder with cerebellar ataxia and dystonic tremor. KIF1C variants may also cause a hypomyelinating leukoencephalopathy
Septal projections to the nucleus incertus in the rat: Bidirectional pathways for modulation of hippocampal function
Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)−67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum.Grant sponsors: Fundación Alicia Koplowitz Fellowship (to A.M.S.P.), CAPES-Brasil Bex - 4494/09-1 (to F.N.S.) and 4496/09-4 (to C.W.P.) and Fapitec edital #01/08 (to F.N.S.), FIS-isciiiPI10/01399 (to J.S.), National Health and Medical Research Council of Australia - 520299 (to S.M.), 509246, 1005985, and 1005988 (to A.L.G.), the Florey Foundation (to S.M., A.L.G.), Besen Family Foundation (to A.L.G.) and a NEUREN project, FP7-PEOPLE-IRSES PIRSES-GA-2012-318997 (to A.L.G., F.E.O.-B.)
Proposal for best practice in the use of video-EEG when psychogenic non-epileptic seizures are a possible diagnosis
The gold-standard for the diagnosis of psychogenic non-epileptic seizures (PNES) is capturing an attack with typical semiology and lack of epileptic ictal discharges on video-EEG. Despite the importance of this diagnostic test, lack of standardisation has resulted in a wide variety of protocols and reporting practices. The goal of this review is to provide an overview of research findings on the diagnostic video-EEG procedure, in both the adult and paediatric literature. We discuss how uncertainties about the ethical use of suggestion can be resolved, and consider what constitutes best clinical practice. We stress the importance of ictal observation and assessment and consider how diagnostically useful information is best obtained. We also discuss the optimal format of video-EEG reports; and of highlighting features with high sensitivity and specificity to reduce the risk of miscommunication. We suggest that over-interpretation of the interictal EEG, and the failure to recognise differences between typical epileptic and nonepileptic seizure manifestations are the greatest pitfalls in neurophysiological assessment of patients with PNES. Meanwhile, under-recognition of semiological pointers towards frontal lobe seizures and of the absence of epileptiform ictal EEG patterns during some epileptic seizure types (especially some seizures not associated with loss of awareness), may lead to erroneous PNES diagnoses. We propose that a standardised approach to the video-EEG examination and the subsequent written report will facilitate a clear communication of its import, improving diagnostic certainty and thereby promoting appropriate patient management
Consensus Paper: Radiological Biomarkers of Cerebellar Diseases
Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine
The genetics of ataxia: through the labyrinth of the Minotaur, looking for Ariadne’s thread
Les chimiokines, de nouveaux acteurs dans le système dopaminergique
Les travaux pionniers réalisés par notre équipe ont permis de démontrer l’expression
neuronale et gliale de plusieurs chimiokines et de leurs récepteurs dans les voies
dopaminergiques (DA) centrales. Ces travaux posent la question du rôle des chimiokines
dans la physiologie du neurone DA et de leur implication dans un processus pathologique
susceptible d’affecter les voies DA de type dégénératif, comme dans la maladie de
Parkinson pour la voie DA nigro-striée. Nous focaliserons notre attention sur deux
chimiokines particulières, le SDF-1 (CXCL12) et le MCP-1 (CCL2) et leurs récepteurs
respectifs CXCR4 et CCR2, qui sont exprimés par pratiquement tous les neurones DA des
noyaux mésencéphaliques. Nous avons démontré, par plusieurs approches in vivo
et in vitro, que le SDF-1 et le MCP-1 peuvent moduler la
neurotransmission DA dans la voie nigro-striée, modifiant l’état électrique du neurone et
la libération de ce neurotransmetteur via leurs récepteurs spécifiques.
Parmi les mécanismes impliqués dans ces effets, nous avons révélé la mise en jeu de canaux
calciques de type N Ã haut seuil pour le SDF-1 et de canaux potassiques pour le MCP-1.
Nous discutons ensuite l’implication possible du SDF-1 et de son dérivé clivé, le SDF-1
(5-67) dans la survie des neurones DA
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