Tau protein quantification in skin biopsies differentiates tauopathies from alpha-synucleinopathies.

Abnormal accumulation of microtubule-associated protein tau (τ) is a characteristic feature of atypical parkinsonisms with tauopathies, such as progressive supranuclear palsy and corticobasal degeneration. However, pathological τ has also been observed in α-synucleinopathies like Parkinson's disease and multiple system atrophy. Based on the involvement of the peripheral nervous system in several neurodegenerative diseases, we characterized and compared τ expression in skin biopsies of patients clinically diagnosed with Parkinson's disease, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration and in healthy control subjects. In all groups, τ protein was detected along both somatosensory and autonomic nerve fibres in the epidermis and dermis by immunofluorescence. We found by western blot the presence of mainly two different bands at 55 and 70 kDa, co-migrating with 0N4R/1N3R and 2N4R isoforms, respectively. At the RNA level, the main transcript variants were 2N and 4R, and both were more expressed in progressive supranuclear palsy/corticobasal degeneration by real-time PCR. Enzyme-linked immunosorbent assay demonstrated significantly higher levels of total τ protein in skin lysates of progressive supranuclear palsy/corticobasal degeneration compared to the other groups. Multivariate regression analysis and receiver operating characteristics curve analysis of τ amount at both sites showed a clinical association with tauopathies diagnosis and high diagnostic value for progressive supranuclear palsy/corticobasal degeneration versus Parkinson's disease (sensitivity 90%, specificity 69%) and progressive supranuclear palsy/corticobasal degeneration versus multiple system atrophy (sensitivity 90%, specificity 86%). τ protein increase correlated with cognitive impairment in progressive supranuclear palsy/corticobasal degeneration. This study is a comprehensive characterization of τ in the human cutaneous peripheral nervous system in physiological and pathological conditions. The differential expression of τ, both at transcript and protein levels, suggests that skin biopsy, an easily accessible and minimally invasive exam, can help in discriminating among different neurodegenerative diseases.

Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core.

In neuronal cells, tau is a microtubule-associated protein placed in axons and alpha synuclein is enriched at presynaptic terminals. They display a propensity to form pathologic aggregates, which are considered the underlying cause of Alzheimer's and Parkinson's diseases. Their functional impairment induces loss of axonal transport, synaptic and mitochondrial disarray, leading to a "dying back" pattern of degeneration, which starts at the periphery of cells. In addition, pathologic spreading of alpha-synuclein from the peripheral nervous system to the brain through anatomical connectivity has been demonstrated for Parkinson's disease. Thus, examination of the extent and types of tau and alpha-synuclein in peripheral tissues and their relation to brain neurodegenerative diseases is of relevance since it may provide insights into patterns of protein aggregation and neurodegeneration. Moreover, peripheral nervous tissues are easily accessible in-vivo and can play a relevant role in the early diagnosis of these conditions. Up-to-date investigations of tau species in peripheral tissues are scant and have mainly been restricted to rodents, whereas, more evidence is available on alpha synuclein in peripheral tissues. Here we aim to review the literature on the functional role of tau and alpha synuclein in physiological conditions and disease at the axonal level, their distribution in peripheral tissues, and discuss possible commonalities/diversities as well as their interaction in proteinopathies.

Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function.

The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state.

Levodopa-induced dyskinesia in Parkinson disease: Sleep matters.

OBJECTIVE: The spectrum of clinical symptom changes during the course of Parkinson disease (PD). Levodopa therapy, while offering remarkable control of classical motor symptoms, causes abnormal involuntary movements as the disease progresses. This levodopa-induced dyskinesia (LID) has been associated with abnormal cortical plasticity. Because slow wave activity (SWA) of nonrapid eye movement (NREM) sleep underlies adjustment of cortical excitability, we sought to elucidate the relationship between this physiological process and LID. METHODS: Thirty-six patients at different stages of PD underwent whole-night video polysomnography-high-density electroencephalography (vPSG-hdEEG), preceded by 1 week of actigraphy. To represent the broad spectrum of the disease, patients were divided into 3 groups by disease stage-(1) de novo (n = 9), (2) advanced (n = 13), and (3) dyskinetic (DYS; n = 14)-were compared to an age-matched control group (n = 12). The SWA-NREM content of the vPSG-hdEEG was then temporally divided into 10 equal parts, from T1 to T10, and power and source analyses were performed. T2-T3-T4 were considered early sleep and were compared to T7-T8-T9, representing late sleep. RESULTS: We found that all groups, except the DYS group, manifested a clear-cut SWA decrease between early and late sleep. INTERPRETATION: Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LID. Ann Neurol 2018;84:905-917.

From physiological neck myoclonus to sleep related head jerk.

Neck myoclonus (NM) is a frequent recently described sleep-related motor phenomenon occurring mainly during REM sleep with uncertain effect on sleep continuity. To better describe this phenomenon we studied 11 consecutive drug-free patients undergoing a video-polysomnographic (V-PSG) study who present at least 5 NM events in one single night of recording. All events were measured and checked for their association with rapid eye and leg movements, EEG arousals, awakenings and Bereitschaftspotential. One hundred and eighty-two motor events from 11 subjects were analyzed. Motor events were approximately 0.5 s in duration and occurred during REM sleep in 79.7% of the cases. Only 14.8% of the events were associated with rapid eye movements, 52.2% with leg movements, while approximately 80% of them were accompanied by an arousal or awakening. No EEG abnormalities and Bereitschaftspotential were observed. For its duration and its segregation in sleep, NM could be more appropriately named "sleep-related head jerks" (SRHJ). SRHJ should be recognized and its effect on sleep stability should be re-considered.

Deep Brain Stimulation for Tremor: Is There a Common Structure?

BACKGROUND: Subthalamic nucleus (STN) stimulation has been recognized to control resting tremor in Parkinson disease. Similarly, thalamic stimulation (ventral intermediate nucleus; VIM) has shown tremor control in Parkinson disease, essential, and intention tremors. Recently, stimulation of the posterior subthalamic area (PSA) has been associated with excellent tremor control. Thus, the optimal site of stimulation may be located in the surrounding white matter. AIMS: The objective of this work was to investigate the area of stimulation by determining the contact location correlated with the best tremor control in STN/VIM patients. METHODS: The mean stimulation site and related volume of tissue activated (VTA) of 25 tremor patients (STN or VIM) were projected on the Morel atlas and compared to stimulation sites from other tremor studies. RESULTS: All patients showed a VTA that covered ≥50% of the area superior and medial to the STN or inferior to the VIM. Our stimulation areas suggest involvement of the more lateral and superior part of the dentato-rubro-thalamic tract (DRTT), whereas targets described in other studies seem to involve the DRTT in its more medial and inferior part when it crosses the PSA. CONCLUSIONS: According to anatomical and diffusion tensor imaging data, the DRTT might be the common structure stimulated at different portions within the PSA/caudal zona incerta.

Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson's disease.

Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson's disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS. We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation. The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

Cortical reorganisation of cerebral networks after childhood stroke: impact on outcome.

BACKGROUND: Recovery after arterial ischaemic stroke is known to largely depend on the plastic properties of the brain. The present study examines changes in the network topography of the developing brain after stroke. Effects of brain damage are best assessed by examining entire networks rather than single sites of structural lesions. Relating these changes to post-stroke neuropsychological variables and motor abilities will improve understanding of functional plasticity after stroke. Inclusion of healthy controls will provide additional insight into children's normal brain development. Resting state functional magnetic resonance imaging is a valid approach to topographically investigate the reorganisation of functional networks after a brain lesion. Transcranial magnetic stimulation provides complementary output information. This study will investigate functional reorganisation after paediatric arterial ischaemic stroke by means of resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a cross-sectional plus longitudinal study design. The general aim of this study is to better understand neuroplasticity of the developing brain after stroke in order to develop more efficacious therapy and to improve the post-stroke functional outcome. METHODS: The cross-sectional part of the study will investigate the functional cerebral networks of 35 children with chronic arterial ischaemic stroke (time of the lesion >2 years). In the longitudinal part, 15 children with acute arterial ischaemic stroke (shortly after the acute phase of the stroke) will be included and investigations will be performed 3 times within the subsequent 9 months. We will also recruit 50 healthy controls, matched for age and sex. The neuroimaging and neurophysiological data will be correlated with neuropsychological and neurological variables. DISCUSSION: This study is the first to combine resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a paediatric population diagnosed with arterial ischaemic stroke. Thus, this study has the potential to uniquely contribute to the understanding of neuronal plasticity in the brains of healthy children and those with acute or chronic brain injury. It is expected that the results will lead to the development of optimal interventions after arterial ischaemic stroke.

Directional deep brain stimulation: an intraoperative double-blind pilot study.

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinson's disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in omnidirectional mode, compared with 4.2 mm(3) when only one electrode was used. Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the subthalamic nucleus as well as in the nucleus ventralis intermedius of the thalamus significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.

Efficacy of transcranial magnetic stimulation treatment in reducing neuropsychiatric symptomatology after traumatic brain injury.

Background: Neuropsychiatric disorders are highly disabling in traumatic brain injury (TBI) patients, and psychopharmacological treatments often fail to adequately mitigate their detrimental effects. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment in neurology and psychiatry, showing potential in treating psychiatric disorders. Objective: This study investigates the efficacy of a novel, dual-site sequential rTMS protocol designed to treat neuropsychiatric symptoms in a TBI patient who was refractory to conventional treatments. Methods: A 34-year-old woman with severe head trauma and complex psychopathology underwent 20 daily sessions of focal-coil rTMS, combining inhibitory stimulation (1 Hz) on the right dorsolateral prefrontal cortex (DLPFC) and excitatory (10 Hz) on the left DLPFC, guided by a neuronavigation system. Psychiatric and neurocognitive assessments were conducted at baseline and at 2, 4, and 8 weeks following the beginning of rTMS treatment. Results: After 2 weeks of treatment, the patient showed decreased impulsivity and obsessive-compulsive symptoms, along with improvements in attention and processing speed. After 4 weeks, impulsivity further declined, though no other significant changes were noted. At 8 weeks, a persistent positive effect was observed, including enhanced positive emotions. Discussion: These findings suggest that guided, alternating neurostimulation of the DLPFC may modulate activity within cortico-striato-thalamo-cortical circuits, providing a promising alternative for managing neuropsychiatric symptoms in TBI patients who are resistant to traditional treatments.

Automated online safety margin (GLIOVIS) for glioma surgery model.

Purpose: Glioblastoma is the most common type of primary brain malignancy and has a poor prognosis. The standard treatment strategy is based on maximal safe surgical resection followed by radiotherapy and chemotherapy. Surgical resection can be optimized by using 5-delta-aminolevulinic acid (5-ALA)-induced fluorescence, which is the current mainstay. Although 5-ALA-induced fluorescence has gained general acceptance, it is also limited by inter-observer variability and non-standardized fluorescence parameters. We present a new software for processing images analysis to better recognize the tumor infiltration margins using an intraoperative immediate safety map of 5-ALA-induced fluorescence. We tested this in a brain model using a commercial surgical exoscope. Methods: A dedicated software GLIOVIS (ACQuF-II, Advanced Colorimetry-based Quantification of Fluorescence) was designed for processing analysis of images taken on the Intraoperative Orbital Camera Olympus Orbeye (IOC) to determine the relative quantification of Protoporphyrin IX (5-ALA metabolite) fluorescence. The software allows to superpose the new fluorescence intensity map and the safety margins over the original images. The software was tested on gel-based brain models. Results: Two surrogate models were developed: PpIX agarose gel-integrated in gelatin-based brain model at different scales (1:25 and 1:1). The images taken with the IOC were then processed using GLIOVIS. The intensity map and safety margins could be obtained for all available models. Conclusions: GLIOVIS for 5-ALA-guided surgery image processing was validated on various gelatin-based brain models. Different levels of fluorescence could be qualitatively digitalized using this technique. These results need to be further confirmed and corroborated in vivo and validated clinically in order to define a new standard of care for glioblastoma resection.

Feasibility of Adjunct Therapy with a Robotic Hand Orthosis after Botulinum Toxin Injections in Persons with Spasticity: A Pilot Study.

Upper-limb spasticity, frequent after central nervous system lesions, is typically treated with botulinum neurotoxin type A (BoNT-A) injections to reduce muscle tone and increase range of motion. However, performing adjunct physical therapy post-BoNT-A can be challenging due to residual weakness or spasticity. This study evaluates the feasibility of hand therapy using a robotic hand orthosis (RELab tenoexo) with a mobile phone application as an adjunct to BoNT-A injections. Five chronic spastic patients participated in a two-session pilot study. Functional (Box and Block Test (BBT), Action Research Arm Test (ARAT)), and muscle tone (Modified Ashworth Scale (MAS)) assessments were conducted to assess functional abilities and impairment, along with usability evaluations. In the first session, subjects received BoNT-A injections, and then they performed a simulated unsupervised therapy session with the RELab tenoexo in a second session a month later. Results showed that BoNT-A reduced muscle tone (from 12.2 to 7.4 MAS points). The addition of RELab tenoexo therapy was safe, led to functional improvements in four subjects (two-cube increase in BBT as well as 2.8 points in grasp and 1.3 points in grip on ARAT). Usability results indicate that, with minor improvements, adjunct RELab tenoexo therapy could enhance therapy doses and, potentially, long-term outcomes.

Biometry extraction and probabilistic anatomical atlas of the anterior Visual Pathway using dedicated high-resolution 3-D MRI.

Anterior Visual Pathway (aVP) damage may be linked to diverse inflammatory, degenerative and/or vascular conditions. Currently however, a standardized methodological framework for extracting MRI biomarkers of the aVP is not available. We used high-resolution, 3-D MRI data to generate a probabilistic anatomical atlas of the normal aVP and its intraorbital (iOrb), intracanalicular (iCan), intracranial (iCran), optic chiasm (OC), and tract (OT) subdivisions. We acquired 0.6 mm3 steady-state free-precession images from 24 healthy participants using a 3 T scanner. aVP masks were obtained by manual segmentation of each aVP subdivision. Mask straightening and normalization with cross-sectional area (CSA) preservation were obtained using scripts developed in-house. A probabilistic atlas ("aVP-24") was generated by averaging left and right sides of all subjects. Leave-one-out cross-validation with respect to interindividual variability was performed employing the Dice Similarity Index (DSI). Spatially normalized representations of the aVP subdivisions were generated. Overlapping CSA values before and after normalization demonstrate preservation of the aVP cross-section. Volume, length, CSA, and ellipticity index (ε) biometrics were extracted. The aVP-24 morphology followed previous descriptions from the gross anatomy. Atlas spatial validation DSI scores of 0.85 in 50% and 0.77 in 95% of participants indicated good generalizability across the subjects. The proposed MRI standardization framework allows for previously unavailable, geometrically unbiased biometric data of the entire aVP and provides the base for future spatial-resolved, group-level investigations.

Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies.

Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson's disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0.825), while CBD vs HC / PD (AUC 0.797), and PSP vs MSA (AU 0.778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.

Slow wave activity across sleep-night could predict levodopa-induced dyskinesia.

A disruption in the slow wave activity (SWA) mediated synaptic downscaling process features Parkinson's disease (PD) patients presenting levodopa-induced dyskinesia (LID). To corroborate the role of SWA in LID development, 15 PD patients with LID, who underwent a polysomnography before LID's appearance, were included. Slow wave sleep epochs were extracted, combined and segmented into early and late sleep. SWA power was calculated. A linear regression model established that the SWA overnight decrease could predict the time to the emergence of LID. Our finding supports the link between SWA-mediated synaptic downscaling and the development of LID. If confirmed, it could pave the way to the study of possible sleep targeted therapies able to protect PD patients from LID development.

Amyloid detection and typing yield of skin biopsy in systemic amyloidosis and polyneuropathy.

OBJECTIVE: Disease-modifying therapies are available for amyloidosis but are ineffective if end-organ damage is severe. As small fiber neuropathy is an early and common feature of amyloidosis, we assessed detection and typing yield of skin biopsy for amyloid in patients with confirmed systemic amyloidosis and neuropathic symptoms. METHODS: In this case-control study, patients with transthyretin and light chain amyloidosis (ATTRv, ATTRwt, and AL) were consecutively recruited. They were sex and age-matched to three control groups (1) non-neuropathic controls (NNC), (2) monoclonal gammopathy of undetermined significance (MGUS), and (3) other neuropathic disease controls (ONC). Patients underwent a double 3 mm skin biopsy in proximal and distal leg. Amyloid index and burden, protein typing by immuno-electron microscopy, intraepidermal nerve fiber density, electroneuromyography, and clinical characteristics were analyzed. RESULTS: We studied 15 subjects with confirmed systemic amyloidosis, 20 NNC, 18 MGUS, and 20 ONC. Amyloid was detected in 100% of patients with amyloidosis (87% in ankle and 73% in thigh). It was not detected in any of the control groups. A small fiber neuropathy was encountered in 100% of amyloidosis patients, in 80% of MGUS, and in 78% of ONC. Amyloid burden was higher in ATTRv, followed by AL and ATTRwt. The ultrastructural examination allowed the identification of the precursor protein by immunotyping in most of the cases. INTERPRETATION: Skin biopsy is a minimally invasive test with optimal sensitivity for amyloid. It allows amyloid typing by electron microscope to identify the precursor protein. The diagnostic work up of systemic amyloidosis should include a skin biopsy.

Transcranial Magnetic Stimulation Improves Executive Functioning through Modulation of Social Cognitive Networks in Patients with Mild Cognitive Impairment: Preliminary Results.

(1) Background: Patients with mild cognitive impairment (MCI) often present impairment in executive functions (EFs). This study aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on EFs in patients with MCI. (2) Methods: A prospective trial was conducted on 11 patients with MCI. Participants underwent 25 min of 20 Hz rTMS for ten days on the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC). Before (T0) and after rTMS treatment (T1), global cognitive profile and EFs were investigated using the Montreal cognitive assessment (MoCA), trial making test (TMT) A and B, and frontal assessment battery (FAB). Depression symptoms were assessed using the geriatric depression scale (GDS). Statistical analysis included Wilcoxon signed-rank test. (3) Results: After treatment, patients showed a significant improvement in the MoCA EFs subtask (T0 vs. T1, p = 0.015) and TMT-B (T0 vs. T1, p = 0.028). Five MCI patients with EF impairment showed full recovery of these deficits. No significant changes in the GDS were observed. (4) Conclusions: rTMS stimulation over the TPJ and MPFC induced significant short-term improvements in EFs in MCI patients. These findings suggest that the TPJ and MPFC may be involved in the attention-executive skills to redirect attention toward behaviorally relevant stimuli.

Deep brain stimulation of the globus pallidus internal improves symptoms of chorea-acanthocytosis.

Chorea-acanthocytosis is a rare autosomal recessive disorder. To date, treatment is only symptomatic and supportive. Results from the few reports of chorea-acanthocytosis patients treated with deep brain stimulation (DBS) have been inconsistent. We present case reports for two patients with chorea-acanthocytosis who received DBS treatment and compare the outcomes with results from the literature. Both patients showed the typical clinical features of chorea-acanthocytosis with motor symptoms resistant to medical treatment. Chorea was significantly improved following low-frequency DBS treatment in both patients. However, dystonia was only mildly improved. Four chorea-acanthocytosis patients treated with DBS treatment have been reported in the literature. One patient had improvement with low-frequency DBS stimulation, while another two had improvement with higher-frequency DBS. One patient, however, did not improve with either low-frequency or high-frequency DBS. Bilateral DBS to the GPi can improve chorea and dystonia in some patients with intractable chorea-acanthocytosis. However, selection criteria for the most promising candidates must be defined, and the long-term benefits evaluated in clinical studies.

Impairment of sleep homeostasis in cervical dystonia patients.

Alterations in brain plasticity seem to play a role in the pathophysiology of cervical dystonia (CD). Since evidences indicate that sleep regulates brain plasticity, we hypothesized that an alteration in sleep homeostatic mechanisms may be involved in the pathogenesis of CD. We explored sleep in control subjects (CTL) and CD patients before (Tpre-BoNT) and after (Tpost-BoNT) botulinum toxin (BoNT) treatment. A physiological slow wave activity (SWA) power decrease throughout the night was observed in CTL but not in CD at Tpre-BoNT. BoNT restored the physiological SWA decrease in CD at Tpost-BoNT. Furthermore, in the first part of the night, CD at Tpost-BNT showed a frontal increase and parietal decrease in SWA power compared to CD at Tpre-BoNT, with a SWA distribution comparable to that observed in CTL. Our data highlighted a pathophysiological relationship between SWA during sleep and CD and provided novel insight into the transient central plastic effect of BoNT.

Imagined paralysis reduces motor cortex excitability.

Mental imagery is a powerful capability that engages similar neurophysiological processes that underlie real sensory and motor experiences. Previous studies show that motor cortical excitability can increase during mental imagery of actions. In this study, we focused on possible inhibitory effects of mental imagery on motor functions. We assessed whether imagined arm paralysis modulates motor cortical excitability in healthy participants, as measured by motor evoked potentials (MEPs) of the hand induced by near-threshold transcranial magnetic stimulation (TMS) over the primary motor cortex hand area. We found lower MEP amplitudes during imagined arm paralysis when compared to imagined leg paralysis or baseline stimulation without paralysis imagery. These results show that purely imagined bodily constraints can selectively inhibit basic motor corticospinal functions. The results are discussed in the context of motoric embodiment/disembodiment.