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Background Transmission of all known pathogenic orthohantaviruses (family Hantaviridae) usually occurs via inhalation of aerosols contaminated with viral particles derived from infected rodents and organ manifestation of infections is characterized by lung and kidney involvement. Orthohantaviruses found in Eurasia cause hemorrhagic fever with renal syndrome (HFRS) and New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS). However, cases of infection with Old World orthohantaviruses with severe pulmonary manifestations have also been observed. Therefore, human airway cells may represent initial targets for orthohantavirus infection and may also play a role in the pathogenesis of infections with Eurasian orthohantaviruses. Methods We analyzed the permissiveness of primary endothelial cells of the human pulmonary microvasculature and of primary human epithelial cells derived from bronchi, bronchioles and alveoli for Old World orthohantavirus Puumala virus (PUUV) in vitro. In addition, we examined the expression of orthohantaviral receptors in these cell types. To minimize donor-specific effects, cells from two different donors were tested for each cell type. Results Productive infection with PUUV was observed for endothelial cells of the microvasculature and for the three tested epithelial cell types derived from different sites of the respiratory tract. Interestingly, infection and particle release were also detected in bronchial and bronchiolar epithelial cells although expression of the orthohantaviral receptor integrin β3 was not detectable in these cell types. In addition, replication kinetics and viral release demonstrate enormous donor-specific variations. Conclusions The human respiratory epithelium is among the first targets of orthohantaviral infection and may contribute to virus replication, dissemination and pathogenesis of HFRS-causing orthohantaviruses. Differences in initial pulmonary infection due to donor-specific factors may play a role in the observed broad variance of severity and symptoms of orthohantavirus disease in patients. The absence of detectable levels of integrin αVβ3 surface expression on bronchial and small airway epithelial cells indicates an alternate mode of orthohantaviral entry in these cells that is independent from integrin β3.

Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. Hantavirus patients showed significantly increased urinary nephrin, IgG and serum suPAR concentrations compared to healthy controls. Nephrin and IgG levels were significantly higher in patients with severe proteinuria than with mild proteinuria, and nephrin correlated strongly with biomarkers of glomerular proteinuria over time. Congruently, electron microcopy analyses showed a focal podocyte foot process effacement. suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a pathophysiological mediator in podocyte dysfunction. In contrast to INS, proteinuria recovered autonomously in hantavirus patients. This study reveals podocyte injury as main cause of proteinuria in hantavirus patients. A better understanding of the regenerative nature of hantavirus-induced glomerulopathy may generate new therapeutic approaches for INS.

The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation. We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108–189 min postoperatively), and rotational fluoroscopies (4–9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28–182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an “iron sight” (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°). In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5–6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5–35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups. D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.

Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived circulating signaling molecule that has been implicated in chronic kidney disease, such as focal segmental glomerulosclerosis (FSGS). Typically, native uPAR (isoform 1) translates to a 3-domain protein capable of binding and activating integrins, yet the function of additional isoforms generated by alternative splicing is unknown. Here, we characterized mouse uPAR isoform 2 (msuPAR2), encoding domain I and nearly one-half of domain II, as a dimer in solution, as revealed by 3D electron microscopy structural analysis. In vivo, msuPAR2 transgenic mice exhibited signs of severe renal disease characteristic of FSGS with proteinuria, loss of kidney function, and glomerulosclerosis. Sequencing of the glomerular RNAs from msuPAR2-Tg mice revealed a differentially expressed gene signature that includes upregulation of the suPAR receptor Itgb3, encoding β3 integrin. Crossing msuPAR2-transgenic mice with 3 different integrin β3 deficiency models rescued msuPAR2-mediated kidney function. Further analyses indicated a central role for β3 integrin and c-Src in msuPAR2 signaling and in human FSGS kidney biopsies. Administration of Src inhibitors reduced proteinuria in msuPAR2-transgenic mice. In conclusion, msuPAR2 may play an important role in certain forms of scarring kidney disease.

Orthohantaviruses Hantaan (HTNV) and Puumala (PUUV) virus cause hemorrhagic fever with renal syndrome (HFRS), that is characterized by acute renal failure with often massive proteinuria and by morphological changes of the tubular and glomerular apparatus. Orthohantaviral N protein is found in renal cells and plays a key role in replication. However, the replication in human renal cells is not well characterized. Therefore, we examined the orthohantaviral infection in different human renal cells. Differences in localization of N protein, release of particles, and modulation of the actin cytoskeleton between both virus species are observed in human renal cells. A substantial portion of HTNV N protein demonstrates a filamentous pattern in addition to the typical punctate pattern. Release of HTNV depends on an intact actin and microtubule cytoskeleton. In contrast, PUUV N protein is generally localized in a punctate pattern and release of PUUV does not require an intact actin cytoskeleton. Infection of podocytes results in cytoskeletal rearrangements that are more pronounced for HTNV. Analyzing Vero E6 cells revealed differences compared to human renal cells. The pattern of N proteins is strictly punctate, release does not depend on an intact actin cytoskeleton and cytoskeletal rearrangements are not present. No virus-specific variations between HTNV and PUUV are observed in Vero E6 cells. Using human renal cells as cell culture model for orthohantavirus infection demonstrates virus-specific differences and orthohantavirus-induced cytoskeletal rearrangements that are not observed in Vero E6 cells. Therefore, the choice of an appropriate cell culture system is a prerequisite to study orthohantavirus pathogenicity.

Trois jours apres chirurgie de la hanche, un patient âge de 76 ans a developpe sous traitement prophylactique antibiotique peri-operatoire un etat aigu de confusion, des cephalees, de la fievre, des nausees, des vomissements et une incontinence urinaire.

Ein 76-jahriger Patient entwickelte drei Tage nach Huftoperation unter perioperativer Antibiotikaprophylaxe einen akuten Verwirrtheitszustand, Kopfschmerzen, Fieber, Ubelkeit, Erbrechen und eine Urininkontinenz.

Freezing of gait (FOG) in Parkinson’s disease (PD) occurs frequently in situations with high environmental complexity. The supplementary motor cortex (SMC) is regarded as a major network node that exerts cortical input for motor control in these situations. We aimed at assessing the impact of single-session (excitatory) intermittent theta burst stimulation (iTBS) of the SMC on established walking during FOG provoking situations such as passing through narrow spaces and turning for directional changes. Twelve PD patients with FOG underwent two visits in the off-medication state with either iTBS or sham stimulation. At each visit, spatiotemporal gait parameters were measured during walking without obstacles and in FOG-provoking situations before and after stimulation. When patients passed through narrow spaces, decreased stride time along with increased stride length and walking speed (i.e., improved gait) was observed after both sham stimulation and iTBS. These effects, particularly on stride time, were attenuated by real iTBS. During turning, iTBS resulted in decreased stride time along with unchanged stride length, a constellation compatible with increased stepping frequency. The observed iTBS effects are regarded as relative gait deterioration. We conclude that iTBS over the SMC increases stepping frequency in PD patients with FOG, particularly in FOG provoking situations.

Supplemental Digital Content is Available in the Text. An original tool to distinguish Parkinson disease-related from non-Parkinson disease-related pain and to classify it into 3 mechanistic pain descriptors., Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.

Highlights • Clusters of decreased grey matter were associated with lateral flexion of the trunk. • Robust clusters were found in the posterior parietal cortex and the thalamus. • A tilt of the SVV correlated with the degree of trunk deviation. • Grey matter values from the thalamic cluster correlated with the SVV estimates., Background Disruption of central networks, particularly of those responsible for integrating multimodal afferents in a spatial reference frame, were proposed in the pathophysiology of lateral trunk flexion in Parkinson’s disease (PD). Knowledge about the underlying neuroanatomical structures is limited. Objective To investigate if decreased focal grey matter (GM) is associated with trunk flexion to the side and if the revealed GM clusters correlate with a disturbed perception of verticality in PD. Methods 37 PD patients with and without lateral trunk flexion were recruited. Standardized photos were taken from each patient and trunk orientation was measured by a blinded rater. Voxel-based morphometry (VBM) was used to detect associated clusters of decreased GM. The subjective visual vertical (SVV) was assessed as a marker for perception of verticality and SVV estimates were correlated with GM clusters. Results VBM revealed clusters of decreased GM in the right posterior parietal cortex and in the right thalamus were associated with lateral trunk flexion. The SVV correlated with the extent of trunk flexion, and the side of the SVV tilt correlated with the side of trunk flexion. GM values from the thalamus correlated with the SVV estimates. Conclusions We report an association between neurodegenerative changes within the posterior parietal cortex and the thalamus and lateral trunk flexion in PD. These brain structures are part of a network proposed to be engaged in postural control and spatial self-perception. Disturbed perception of verticality points to a shifted egocentric spatial reference as an important pathophysiological feature.

Automatic anatomical segmentation of patients’ anatomical structures and modeling of the volume of tissue activated (VTA) can potentially facilitate trajectory planning and post-operative programming in deep brain stimulation (DBS). We demonstrate an approach to evaluate the accuracy of such software for the ventral intermediate nucleus (VIM) using directional leads. In an essential tremor patient with asymmetrical brain anatomy, lead placement was adjusted according to the suggested segmentation made by the software (Brainlab). Postoperatively, we used directionality to assess lead placement using side effect testing (internal capsule and sensory thalamus). Clinical effects were then compared to the patient-specific visualization and VTA simulation in the GUIDE™ XT software (Boston Scientific). The patient’s asymmetrical anatomy was correctly recognized by the software and matched the clinical results. VTA models matched best for dysarthria (6 out of 6 cases) and sensory hand side effects (5/6), but least for facial side effects (1/6). Best concordance was observed for the modeled current anterior and back spread of the VTA, worst for the current side spread. Automatic anatomical segmentation and VTA models can be valuable tools for DBS planning and programming. Directional DBS leads allow detailed postoperative assessment of the concordance of such image-based simulation and visualization with clinical effects.

The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation.We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108-189 min postoperatively), and rotational fluoroscopies (4-9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28-182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an "iron sight" (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°).In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5-6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5-35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups.D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.

Mit der Entwicklung des hochintensiven Magnetresonanztomographie(MRT)-gesteuerten fokussierten Ultraschalls (MRTgFUS) steht der lasionellen stereotaktischen funktionellen Neurochirurgie eine neue Behandlungstechnik zur Verfugung. Hieraus ergeben sich neue, inzisionslose Interventionsansatze in der Therapie von Tremorerkrankungen, deren Sicherheit und Wirksamkeit durch erste Studienergebnisse belegt sind. Dieser Artikel umfasst eine Beschreibung der zugrunde liegenden Ultraschalltechnik, des Ablaufs einer MRTgFUS-Behandlung, einen orientierenden Vergleich zu alternativen offenen und inzisionslosen Interventionstechniken sowie eine Zusammenfassung der aktuellen Evidenz der MRTgFUS-Behandlung im Kontext der lasionellen Tremortherapie. Narrativer Literaturvergleich. In Abhangigkeit von Zielpunkt und Tremoratiologie zeigen bisherige publizierte Ergebnisse der MRTgFUS-Behandlung eine bis zu 80 %ige Reduktion der Tremorintensitat nach 6 bis 12 Monaten Nachkontrolle ohne die Nachteile einer offenen Schadeloperation. Die MRTgFUS-Technologie wird in der funktionellen Neurochirurgie bislang nur an wenigen Studienzentren weltweit angewandt. Neben dem thalamischen ventralen intermediaren Nukleus (V.im.) als Zielpunkt liegen auch erste Studien zur Ablation subthalamischer Faserbahnen vor. Bisherige Studienergebnisse deuten auf eine effektive und sichere Tremortherapie durch die MRTgFUS-Behandlung hin. Die inzisionslose lasionelle Chirurgie mittels MRTgFUS stellt eine wesentliche Erweiterung des Interventionsspektrums fur die funktionelle stereotaktische Neurochirurgie und eine potenziell relevante Alternative zu etablierten interventionellen Therapieoptionen fur Tremor dar.

Background and purpose Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. Methods This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. Results Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. Conclusions Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk.

Background Hemorrhagic fever with renal syndrome (HFRS) caused by pathogenic hantaviruses in Europe and Asia is often characterized by acute kidney injury (AKI) with massive proteinuria. Renal filtration depends on the integrity of epithelial and endothelial monolayers in the tubular and glomerular apparatus. Tubular and glomerular cells represent target cells of hantavirus infection. However, the detailed mechanisms of renal impairment induced by hantaviruses are not well understood. Methods We analyzed the cellular consequences of hantavirus infection by measuring adhesion and migration capacity of human renal cells infected with Puumala (PUUV) or Hantaan (HTNV) virus. The impact of hantaviral nucleocapsid proteins (N proteins) on motility was examined by transfection of podocytes. Results Infection of kidney cells with hantavirus species PUUV and HTNV causes a significant reduction of migration capacity. The impaired motility depends on viral replication and transfection of podocytes with N protein of PUUV or HTNV reveals that the expression of N protein alone is sufficient to deteriorate podocyte function. The cellular effects are more pronounced for the more pathogenic HTNV than for PUUV that causes a milder form of HFRS. Conclusions The direct impairment of migration capacity of renal cells by hantaviral N proteins may contribute substantially to proteinuria observed in the clinical picture of hantavirus infection.

The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data.This article encompasses a description of the technological basis and typical course of MRIgFUS interventions, a comparison to alternative open or incisionless surgical techniques as well as a review of the current evidence base for MRIgFUS ablation in the context of lesional interventions to treat tremor.Narrative literature review and comparison.Depending on the surgical target and tremor etiology published trials of MRIgFUS ablation report a reduction of tremor intensity of up to 80% after 6-12 months follow-up without the disadvantages of open brain surgery.The MRIgFUS functional neurosurgery is conducted only at a limited number of treatment sites. First data on lesions of the thalamic ventral intermediary nucleus (V.im.) as well as subthalamic fiber tracts have been published. These results indicate an effective and safe treatment of tremor disorders by MRIgFUS ablation. Incisionless lesional surgery using MRIgFUS is a significant addition to the interventional armamentarium for functional stereotactic neurosurgery and a potentially valuable alternative to established interventional therapy options for tremor disorders.

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson’s disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article.

Background: The spinal cord is the main pathway for information, connecting the brain and the peripheral nervous system. Any disorder that results in spinal cord dysfunction will have a dramatic impact on the patient's quality of life. This review focusses on myelopathy, specifically, on the acute and subacute clinical presentations and the inflammatory and vascular etiology of this widespread disorder. Summary: Myelopathy following spinal cord injury is a generic term referring to a lesion that affects the spinal cord following traumatic injury, or autoimmune, infectious, neoplastic, vascular and hereditary degenerative diseases. Depending on the patient's medical history, the underlying clinical syndrome and the temporal course of the manifestation, the clinician must account for a wide range of possible differential diagnoses. Key Messages: Spinal cord disorders pose a tremendous challenge for the clinician, as they show great variability in clinical presentation but can have potentially de-vastating sequelae. The acute and sometimes urgent nature of therapeutic management is highly dependent on the underlying disorder, often necessitating a combination of approaches including surgical or conservative therapies (including immunomodulatory therapy) and an interdisciplinary approach to achieve the best outcomes.

Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce.To determine whether nocturnal administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD.Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017. In a single-center study in the sleep laboratory at the University Hospital Zurich, Zurich, Switzerland, 18 patients with PD and EDS (Epworth Sleepiness Scale [ESS] score10) were screened in the sleep laboratory. Five patients were excluded owing to the polysomnographic diagnosis of sleep apnea and 1 patient withdrew consent. Thus, 12 patients were randomized to a treatment sequence (sodium oxybate followed by placebo or placebo followed by sodium oxybate, ratio 1:1) and, after dropout of 1 patient owing to an unrelated adverse event during the washout period, 11 patients completed the study. Two patients developed obstructive sleep apnea during sodium oxybate treatment (1 was the dropout) and were excluded from the per-protocol analysis (n = 10) but included in the intention-to-treat analysis (n = 12).Nocturnal sodium oxybate and placebo taken at bedtime and 2.5 to 4.0 hours later with an individually titrated dose between 3.0 and 9.0 g per night for 6 weeks with a 2- to 4-week washout period interposed.Primary outcome measure was change of objective EDS as electrophysiologically measured by mean sleep latency in the Multiple Sleep Latency Test. Secondary outcome measures included change of subjective EDS (ESS), sleep quality (Parkinson Disease Sleep Scale-2), and objective variables of nighttime sleep (polysomnography).Among 12 patients in the intention-to-treat population (10 men, 2 women; mean [SD] age, 62 [11.1] years; disease duration, 8.4 [4.6] years), sodium oxybate substantially improved EDS as measured objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; P = .002) and subjectively (ESS score, -4.2 points ; 95% CI, -5.3 to -3.0 points; P = .001). Thereby, 8 (67%) patients exhibited an electrophysiologically defined positive treatment response. Moreover, sodium oxybate significantly enhanced subjective sleep quality and objectively measured slow-wave sleep duration (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; P .001). Differences were more pronounced in the per-protocol analysis. Sodium oxybate was generally well tolerated under dose adjustments (no treatment-related dropouts), but it induced de novo obstructive sleep apnea in 2 patients and parasomnia in 1 patient, as detected by polysomnography, all of whom did not benefit from sodium oxybate treatment.This study provides class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD. Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation.clinicaltrials.gov Identifier: NCT02111122.

In seltenen Fällen liegen der erworbenen Schädigung des Nervus peronaeus mit konsekutiver Lähmung der innervierten Muskulatur intraneurale Ganglien zugrunde. Diese können im Gegensatz zu den druckbedingten Kompressionen chirurgisch im Rahmen der Erstdiagnose behandelt werden. Eine sorgfältige Anamnese in Kombination mit einer klinischen und elektrophysiologischen Untersuchung ist hierbei zielführend. Häufig passen einzelne Befunde nicht zu der klassischen Präsentation einer Druckläsion am Fibulakopf. Ergänzend stellt die hochfrequente dynamische Nervensonographie des N. peronaeus eine sensitive und kostengünstige bildgebende Untersuchungsmethode dar, um diese besondere Pathologie aufzudecken. Nachfolgend werden drei Patienten mit Paresen des N. peronaeus beschrieben, bei denen die Nervensonographie zur Diagnose von intraneuralen Ganglien des N. peronaeus führte.

Objective:To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET).Methods:This was a prospective, uncontrolled, single-center interventional study. Patients with ET fulfilling criteria for interventional therapy received unilateral ablation of the cerebellothalamic tract (CTT) by MRIgFUS. Motor symptoms, manual dexterity, cognition, and quality of life were assessed before intervention and at 48 hours and 1, 3, and 6 months after intervention. Rating of standardized video recordings was blinded for evaluation time points. Primary outcome was the change in unilateral hand tremor score of the treated hand.Results:Six patients received MRIgFUS ablation of the CTT contralateral to the treated hand. Repeated-measures comparison determined a statistically significant 83% reduction (before vs 6 months after intervention mean ± SD; absolute reduction; 95% confidence interval) in the unilateral treated hand subscore (14.3 ± 4.9 vs 2.5 ± 2.6; 11.8; 8.4–15.2; p < 0.001), while quality of life improved by 52% (50.5 ± 19.4 vs 24.8 ± 11.4; 25.7; 3.5–47.28; p = 0.046). Measures for manual dexterity, attention and coordination, and overall cognition were unchanged. Transient side effects (n = 3) were ipsilateral hand clumsiness and mild gait instability for up to 3 months.Conclusions:Unilateral MRIgFUS lesioning of the CTT was highly efficacious in reducing contralateral hand tremor in ET without affecting fine motor function and dexterity over 6 months of follow-up. Adverse effects were mild and transient.Classification of evidence:This study provides Class IV evidence that for patients with ET, transcranial MRIgFUS ablation of the cerebellothalamic tract improves tremor.

After bone marrow toxicity, neurological toxicities are the second most common complications of cancer. They can be observed throughout the course of the disease or even after the end of treatment. Establishing the correct diagnosis may be a challenge but is of outmost importance to minimize the risk of long-term neurological deficits and to improve the quality of life of the patients. This review will focus on neurological complications induced by chemotherapeutic agents. As the life expectancy and number of treatment lines used in cancer patients increases, these complications are bound to become more frequent and should be aware to neurologists.

Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinson's disease (PD). Hitherto, most evidence comes from entirely clinical approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG.

In selected cases acquired peroneal palsy is caused by intraneural ganglia. In contrast to the much more frequent "loco typico" lesion which is caused by external pressure, intraneural ganglia can be treated by microscopic nerve surgery as part of primary treatment strategy. A careful clinical history as well as a profound clinical and electrophysiological examination is required to disclose unusual findings. These are common in non-typical peroneal palsy. In this situation high resolution nerve sonography is a fast and sensitive method to detect intraneural ganglia. We report a case series of three patients with peroneal palsy caused by intraneural ganglia and give a review of the literature.In seltenen Fällen liegen der erworbenen Schädigung des Nervus peronaeus mit konsekutiver Lähmung der innervierten Muskulatur intraneurale Ganglien zugrunde. Diese können im Gegensatz zu den druckbedingten Kompressionen chirurgisch im Rahmen der Erstdiagnose behandelt werden. Eine sorgfältige Anamnese in Kombination mit einer klinischen und elektrophysiologischen Untersuchung ist hierbei zielführend. Häufig passen einzelne Befunde nicht zu der klassischen Präsentation einer Druckläsion am Fibulakopf. Ergänzend stellt die hochfrequente dynamische Nervensonographie des N. peronaeus eine sensitive und kostengünstige bildgebende Untersuchungsmethode dar, um diese besondere Pathologie aufzudecken. Nachfolgend werden drei Patienten mit Paresen des N. peronaeus beschrieben, bei denen die Nervensonographie zur Diagnose von intraneuralen Ganglien des N. peronaeus führte.Rarement la lésion du nerf péronier au niveau de la tête fibulaire suivie par une parésie des muscles innervés par ce nerf est causée par un ganglion appuyant sur les structures nerveuses. En ce cas une intervention chirurgicale peut souvant résondre le problème. Une anamnèse soigneusement menée, l'examen neurologique et des investigations neuromusculaires sont essentielles mais souvent atypiques comparés à la lésion péronière «loco typico». L'ultrasonographie à haute résolution est procédée facilement et plus sensible qu'une MRI. Nous allons décrire dans ce papier trois cas de parèsie du nerf péronier pour lesquels la diagnostic final a été posé par ultrasonographie.

Neuere Untersuchungen zur Frage, ob die verbesserten intensivmedizinischen Behandlungsmoglichkeiten zu einer besseren Prognose von komatosen Uberlebende einer kardiopulmonalen Reanimation mit generalisierten Myoklonien gefuhrt haben, liegen unseres Wissens nicht vor. Beziehungen der generalisierten postanoxischen Myoklonien zum konvulsiven Status epilepticus wurden in der Vergangenheit wiederholt angenommen, teils auch kontrovers diskutiert. Wir untersuchten klinisch und elektroenzephalographisch 40 komatose Uberlebende einer kardiopulmonalen Reanimation (18 Frauen, Alter: 26–83 Jahre, mittleres Alter: 58 Jahre; 22 Manner, Alter: 20–79 Jahre, mittleres Alter: 53 Jahre), die in den ersten 24 Stunden generalisierte Myoklonien entwickelt hatten. Die Myoklonien betrafen vor allem das Gesicht, die Oberarm- und Schultermuskulatur und das Diaphragma und konnten ublicherweise durch akustische oder taktile Reize verstarkt oder provoziert werden. Achtunddreisig Patienten hatten ein Burst-Suppression-EEG und 2 Patienten kontinuierliche generalisierte epileptiforme Entladungen. Die intravenose Gabe von Phenytoin, Valproat oder verschiedener Benzodiazepine war meist ineffektiv. Die Myoklonien sistierten mit einer Ausnahme innerhalb von 1–3 Tagen spontan. Funfunddreisig Patienten verstarben innerhalb von 12 Tagen, die ubrigen 5 uberlebten und verblieben im apallischen Syndrom. Generalisierte Myoklonien bei komatosen Uberlebenden einer kardiopulmonalen Reanimation sind ein vorubergehendes, selbstlimitierendes Phanomen. Sie zeigen eine infauste Prognose an, wenn sie mit einem Burst-Suppression-EEG oder generalisierten epileptiformen Entladungen assoziiert sind. Eine umgehend eingeleitete antikonvulsive Behandlung ist meist ineffektiv und hat offenbar keinen Einfluss auf die infauste Prognose dieser Patienten. Bisherige und eigene Erfahrungen zeigen, dass Patienten mit generalisierten postanoxischen Myoklonien—im Gegensatz zum konvulsiven Status epilepticus—eine fast 100%ige Letalitat haben, typischerweise keine EEG-Veranderungen wie beim konvulsiven Status zeigen, weitgehend pharmakotherapie-resistent sind, und die postanaoxischen Myoklonien wahrscheinlich im Hirnstamm generiert werden. Diese Patienten sterben wahrscheinlich an den Folgen der schweren hypoxischen Hirnschadigung und nicht an einer besonders schwer verlaufenden Form des konvulsiven Status epilepticus.

MR imaging-guided high intensity focused ultrasound (MRIgFUS) is a novel, noninvasive technique for the treatment of functional brain disorders through the intact human skull at millimeter precision. The ExAblate 4000 transcranial MRIgFUS system (InSightec, Haifa, Israel) uses a 1024-element phased array transducer, which is attached to the patient’s head via a standard stereotactic frame situated inside a 3T MRI scanner, and is CE certified for interventions in the thalamus, subthalamus and pallidum.

Background There is only limited data on improvements of critical medical care is resulting in a better outcome of comatose survivors of cardiopulmonary resuscitation (CPR) with generalized myoclonus. There is also a paucity of data on the temporal dynamics of electroenephalographic (EEG) abnormalities in these patients. Methods Serial EEG examinations were done in 50 comatose survivors of CPR with generalized myoclonus seen over an 8 years period. Results Generalized myoclonus occurred within 24 hours after CPR. It was associated with burst-suppression EEG (n = 42), continuous generalized epileptiform discharges (n = 5), alpha-coma-EEG (n = 52), and low amplitude (10 μV Conclusion Generalized myoclonus in comatose survivors of CPR still implies a poor outcome despite advances in critical care medicine. Anticonvulsive drugs are usually ineffective. All postanoxic EEG-patterns are transient and followed by a variety of EEG sequences composed of different EEG patterns, each of which is recognized as an unfavourable sign. Different EEG-patterns in anoxic encephalopathy may reflect different forms of neocortical dysfunction, which occur at different stages of a dynamic process finally leading to severe neuronal loss.

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinson's disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D2 receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D2 receptor antagonist fluorine-18 desmethoxyfallypride (18F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180-200 MBq 18F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of 18F-DMFP PET. We found the striatal 18F-DMFP uptake ratio to be significantly (P0.01) reduced in the APS patients (2.44+/-0.42) compared with the healthy control subjects (3.61+/-0.43) and the IPS patients (3.21+/-0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate 18F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider 18F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than 11C-labelled D2 radioligands.