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Absence of a hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense pars compacta of the substantia nigra (referred to as dorsolateral nigral hyperintensity) on iron-sensitive high-field magnetic resonance imaging sequences seems to be a typical finding for patients with Parkinson's disease (PD).This study was undertaken to evaluate the diagnostic value of the dorsolateral nigral hyperintensity in a cohort of patients with neurodegenerative parkinsonism including PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) as well as healthy controls using high-field susceptibility-weighted imaging (SWI) at 3.0 Tesla (T).Absence of dorsolateral nigral hyperintensity was assessed on visual inspection of anonymized 3.0T SWI scans in a case-control study including 148 patients with neurodegenerative parkinsonism (PD: n = 104; MSA: n = 22; PSP: n = 22) and 42 healthy controls.Dorsolateral nigral hyperintensity was absent unilaterally in all patients with MSA or PSP, in 83 of 90 patients with PD, but only in one of the healthy controls resulting in an overall correct classification of 95.2% in discriminating neurodegenerative parkinsonism from controls in the per-protocol analysis. Overall correct classification was 93.2% in the intent-to-diagnose analysis, including also SWI scans with poor quality (12.1% of all scans) for nigral evaluation.Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for neurodegenerative parkinsonian disorders.

In this paper, the η-ρ (efficiency - power density) Pareto front of a 20 kVA Uninterruptible Power Supply (UPS), comprising a Si and SiC hybrid 3-level T-type rectifier and inverter stage, and input / output side filters, is determined. A multi-objective optimization procedure is detailed, which employs an electrical converter model and coupled electro-thermal component models. Each component model determines the corresponding losses, volumes, and temperature rises. A detailed description of the inductor model is given which considers high frequency winding losses as well as core losses, and calculates the temperature rises inside the inductor, e.g. the hot-spot winding temperature. Based on the determined η-ρ Pareto front, the most suitable realization of the proposed UPS system is determined, which is based on the resulting sensitivities of the design parameters (switching frequency, current ripples, magnetic materials, etc.) on the performance of power converter system (efficiency and power density). As a result, a switching frequency of 16 kHz, maximum relative input and output side current ripples of 20%, amorphous core materials for DM inductors, and nanocrystalline core materials for CM inductors are selected in order to achieve a converter efficiency of 96.6% at a power density of 2.3 kVA/dm 3 .

On-chip switched capacitor (SC) converters for multicore microprocessor power delivery have the potential to reduce the overall energy consumption of future multicore microprocessor systems by independently regulating the voltage supply of each core. This paper describes an on-chip SC converter that can be reconfigured between a 2:1 and a 3:2 voltage conversion ratio to support a wide output voltage range from a single input supply. Regarding SC converter analysis and modeling, this paper extends an existing state space model framework to include the flying capacitors' parasitic bottom plate capacitors, which for on-chip SC converters significantly influence both the capacitor currents and the converter efficiency. A reconfigurable SC converter that supports an output voltage range of 700mV to 1150mV from a 1.8V input supply is implemented in a 32nm SOI CMOS technology that features the high-density deep trench capacitor. The converter achieves a maximum efficiency of 85.2% at 2.1W/mm2 power density in the 2:1 configuration and a maximum efficiency of 84.1% at 3.2W/mm2 in the 3:2 configuration.

Multiple system atrophy (MSA) carries a universally poor prognosis, but the natural history of the disease is not well established. A new study prospectively followed a cohort of patients with MSA across multiple centres in the USA. The results provide valuable insight into progression and survival in patients with MSA.

Multiple system atrophy (MSA) is a sporadic and fatal α-synuclein-linked oligodendrogliopathy manifesting with progressive autonomic failure, poorly levodopa-responsive parkinsonism, and cerebellar ataxia, in any combination. Here we review key aspects of MSA integrating important insights from rapidly emerging fields such as genetics, diagnostic work-up including imaging, and translational therapies aimed at disease modification.

A semi-analytical modulation scheme to operate a single-phase, single-stage dual active bridge (DAB) AC-DC converter under full-operating-range zero voltage switching (ZVS) is proposed. The converter topology consists of a DAB DC-DC converter, receiving a rectified AC line voltage via a synchronous rectifier. ZVS modulation strategies previously proposed in literature are either based on current-based (CB) or energy-based (EB) ZVS analyses. The combined phase-shift, duty-cycle, and switching frequency modulation proposed in this paper relies on a novel, current-dependent charge-based (CDCB) ZVS analysis, taking into account the commutation charge of the (parasitic) switch capacitances as well as the time dependency of the commutation currents. Thereby, commutation inductance is shown to be an essential element in achieving full-operating-range ZVS. Experimental results obtained from a 3.7 kW bidirectional electric vehicle battery charger which interfaces a 400 V DC-bus with the 230 Vac, 50 Hz utility grid are given to validate the analysis and practical feasibility of the proposed strategy.

This paper details the weight optimization of forced convection cooling systems, composed of a fan and an extruded-fin heat sink, required for a dc–dc converter of an airborne wind turbine system. The presented investigations detail the optimization of the heat sink's fins with respect to minimum weight and the selection of a suitable fan for minimum overall system weight. A new analytical cooling system model is introduced, and the calculated results are compared to the results determined with a preexisting analytical model and finite-element model simulations. The comparison to experimental results demonstrates the accuracy improvements achieved with the proposed methods. Compared to commercially available products, a weight reduction of 52% is achieved with the proposed optimization procedure for the required heat sink system with $R_{{\rm th},{\rm S}\hbox{-}{\rm a}}=1\ \hbox{K/W}$ .

For a Three-Level Three-phase T-type (3LTTC) rectifier and inverter of a high efficiency Uninterruptible Power Supply (UPS) with an output power of 20 kVA, most suitable semiconductor components are selected. For this purpose, this paper details conduction and switching loss models of T-type rectifiers and inverters, compares the total semiconductor losses achieved for RB-IGBTs and for different types of conventional IGBTs, and evaluates the improvements achieved if the Si rectifier diodes are replaced by SiC Schottky Barrier Diodes (SiC SBDs). The switching loss model is parameterized with measured switching losses. According to the results of this comparison, the rectifier preferably employs RB-IGBTs to realize the bi-directional switch and SiC SBDs for the rectifier diodes; switching frequencies up to 32.5 kHz are feasible for total semiconductor losses of the rectifier of 250W. For the inverter, a realization of the bi-directional switch using an anti-series connection of conventional IGBT/SiC SBD modules is found to be most suitable and facilitates a switching frequency of 19.7 kHz for maximum allowed losses of 250 W.

A common approach for selecting a suitable EMI filter is detailed based on the example of a realized single-phase 500W PFC rectifier. The presented work separates conducted EMI noise into Differential Mode (DM) and Common Mode (CM) components and derives expressions for the DM and CM insertion losses achieved if a given EMI filter is connected to a dedicated power converter. With the use of hardware measurement results it is shown that the impedances of the EMI filter and the PFC rectifier have a considerable impact on the realized insertion losses, which, at particular frequencies, may be even less than approximate worst-case estimations proposed in CISPR 17.

In solid-state-transformer technology, the isolation and power transfer between low voltage and medium voltage side is performed by a high power DC/DC converter. This DC/DC converter provides a defined ratio between input and output voltages, whereby, in order to reduce switching losses, zero-current-switching modulation schemes are often mandatory. The series-resonant-converter operated in half-cycle discontinuous-conduction-mode possesses all the aforementioned features, thus making it highly attractive for solid-state-transformer applications. For this reason, a comprehensive analytical model of the converter's static and dynamic behavior is provided in this paper. In addition, a method to model the switching losses under ZCS conditions, which is based on the behavior of the stored charge in the semiconductors, is presented. This enables an efficiency/power density (η-ρ) Pareto optimization of the aforementioned converter system.

Multiple system atrophy (MSA) is a sporadic and fatal α-synuclein-linked oligodendrogliopathy manifesting with progressive autonomic failure, poorly levodopa-responsive parkinsonism, and cerebellar ataxia, in any combination. Here we review key aspects of MSA integrating important insights from rapidly emerging fields such as genetics, diagnostic work-up including imaging, and translational therapies aimed at disease modification.

Multiple system atrophy (MSA) is an adult-onset atypical parkinsonian disorder (APD) characterized by either rapidly progressive levodopa-unresponsive parkinsonism or a cerebellar syndrome associated with early autonomic failure. According to current consensus criteria two motor subtypes can be distinguished clinically, namely a parkinsonian variant labelled MSA-P and a cerebellar variant labelled MSA-C . Abundant (oligodendro-)glial cytoplasmic inclusions (GCI) represent the histopathological signature lesion that is accompanied by a selective neuronal multisystem degeneration. The principle component of GCIs is α-synuclein, a finding which firmly places MSA among other α-synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Currently, the management of MSA patients is based on symptomatic treatment targeting parkinsonian and autonomic features. Although research into disease-modifying strategies has accelerated, effective neuroprotective treatments are still lacking.

Summary Background Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Interpretation Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials. Funding Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund.

The impact of operating point dependent switching time delays on the output characteristic of a T-type half-bridge is investigated for dc–dc operation. It is found that a series connection of operating point dependent components, i.e., a differential resistance and a voltage source, can accurately reproduce the implications of these switching time delays on the response of the output current of the half-bridge to a step of the duty cycle. This letter details the calculation of these components and verifies the derived expressions by means of experimental results.

Neurogenic orthostatic hypotension is a distinctive and treatable sign of cardiovascular autonomic dysfunction. It is caused by failure of noradrenergic neurotransmission that is associated with a range of primary or secondary autonomic disorders, including pure autonomic failure, Parkinson’s disease with autonomic failure, multiple system atrophy as well as diabetic and nondiabetic autonomic neuropathies. Neurogenic orthostatic hypotension is commonly accompanied by autonomic dysregulation involving other organ systems such as the bowel and the bladder. In the present review, we provide an overview of the clinical presentation, pathophysiology, epidemiology, evaluation and management of neurogenic orthostatic hypotension focusing on neurodegenerative disorders.

The Unified Multiple System Atrophy Rating Scale (UMSARS) was developed to provide a surrogate measure of disease progression in multiple system atrophy. In the present study, the intrarater agreement of the motor examination part of the UMSARS was determined.All patients were first examined face to face, while being video-recorded, by two senior and two junior investigators. The patients' videotaped examinations were reevaluated after 3 months. Intrarater reliability for each item was analyzed by kappa statistics.Overall weighted kappa (κ) values were at least substantial or excellent for all UMSARS motor examination items, except for ocular motor dysfunction, which showed only moderate intrarater agreement. Intrarater reliability was comparable between senior and junior raters, with all κ differences being ≤ 0.22.The motor examination part of the UMSARS was found to have satisfactory intrarater reliability in the present cohort.

The design procedure for a bidirectional DAB dc-dc converter, which provides a high dc voltage of 8kV to the tether of a 100 kW Airborne Wind Turbine (AWT) system, is presented. The maximum allowed weight of the dc-dc converter is 25 kg and, thus, the main challenge is the realization of a light-weight DAB converter. The investigated dc-dc converter is split up into 16 single DAB modules with a rated power of 6.25 kW and a dc port voltage of 2kV. Thus, a weight of less than 25 kg/16 = 1.56 kg needs to be achieved for a single DAB module. The design method used to obtain the minimum weight DAB converter, based on the evaluation of a power-to-weight ratio versus efficiency Pareto Front γ-η-Pareto Front) is presented in this paper. For this purpose the transient voltages and currents of the employed SiC JFETs during switching are discussed in detail, since the respective measurement results allow for a prediction of the switching losses. Moreover, the calculated transformer is realized and experimental results are used to verify the weight, the losses, and the cooling system performance of the transformer. For a single DAB module a weight of m = 1.43 kg, an efficiency of η = 97%, and a power-to-weight ratio of γ = 4.4kW/kg results.

For realizing bidirectional and isolated AC/DC converters, soft-switching techniques/topologies seem to be a favourable choice as they enable a further loss and volume reduction of the system. Contrary to the traditional dual-stage approach, using a power factor corrector (PFC) stage in series with a DC/DC isolation stage, we showed recently that the same functionality can be achieved under full soft-switching operation using a single-stage dual active bridge (DAB) AC/DC converter. This paper investigates the performance of this single-stage approach by comparing it with a state-of-the-art conventional dual-stage concept (both soft-switching converters), where a bidirectional interleaved triangular current mode (TCM) PFC rectifier was chosen in combination with a DAB DC/DC converter. The advantages and drawbacks of each concept are discussed in detail, focusing on the impact of the utilized semiconductor technology and silicon area on the converter efficiency. Furthermore, a comprehensive comparison of power density is allowed by the analytical models that correlate the component losses with their respective volume.

A switching control strategy to enable Zero-Voltage-Switching (ZVS) over the entire input-voltage interval and the full power range of a single-stage Dual Active Bridge (DAB) AC/DC converter is proposed. The converter topology consists of a DAB DC/DC converter, receiving a rectified AC line voltage via a synchronous rectifier. The DAB comprises primary and secondary side full bridges, linked by a high-frequency isolation transformer and inductor. Using conventional control strategies, the soft-switching boundary conditions are exceeded at the higher voltage conversion ratios of the AC input interval. Recently we presented a novel pulse-width-modulation strategy to fully eliminate these boundaries, using a half bridge - full bridge DAB configuration. In this papers the analysis is extended towards a full bridge - full bridge DAB setup, providing more flexibility to minimize the component RMS currents and allowing increased performance (in terms of efficiency and volume). Experimental results are given to validate the theoretical analysis and practical feasibility of the proposed strategy.

For Voltage Regulator Modules (VRM), integrating the power converter with the load in an advanced integration process is a method to deliver power at higher voltage levels, and thereby overcome the high supply current requirements predicted by the 2009 International Technology Roadmap for Semiconductors (ITRS). The most conventional converter type used is the buck or step-down converter. For this converter, the output inductor is recognized as the performance limiting component with respect to efficiency and area requirements. This paper details an inductor optimization procedure for Power Supply in Package (PSiP) and Power Supply on Chip (PwrSoC) applications. Targeting the highest possible efficiency for a specified area-related power density, the optimization procedure determines the best inductor dimensions given the buck converter operating conditions. The optimization procedure is verified using experimental data obtained from a PCB inductor realization. According to the results, the most favorable inductor achieves an efficiency of 94.5% and an area-related power density of 1.97W/mm2 at a switching frequency of 170MHz.

Orthostatic hypotension (OH) is a cardinal feature of autonomic failure in multiple system atrophy (MSA); however, there are few comparative data on OH in the motor subtypes of MSA. In the present retrospective study, postural blood pressure drop after 3 min of standing was determined in 16 patients with the cerebellar variant of MSA (MSA-C) and in 17 patients with the Parkinson variant (MSA-P). Twenty idiopathic Parkinson’s disease (IPD) patients matched for age, sex, disease duration and dopaminergic therapy served as control group. OH frequency and severity were more pronounced in MSA-C followed by MSA-P and IPD. Differences in brainstem pathology are likely to account for the tight association of MSA-C and OH. A simple standing test should be obligatory in the work-up of patients with sporadic late-onset ataxias.

Airborne Wind Turbines (AWT) represent a radically new and fascinating concept for future harnessing of wind power. This concept consists of realizing only the blades of a conventional wind turbine (CWT) in the form of a power kite flying at high speed perpendicular to the wind. On the kite are mounted a turbine, an electrical generator and a power electronics converter. The electric power generated is transmitted via a medium voltage cable to the ground. Because of the high flight speed of the power kite, several times the actual wind speed, only a very small swept area of the turbine is required according to Betz's Law and/or a turbine of low weight for the generation of a given electric power. Moreover, because of the high turbine rotational speed, no gear transmission is necessary and the size of the generator is also reduced. For takeoff and landing of the power kite, the turbines act as propellers and the generators as motors, i.e. electric power is supplied so that the system can be maneuvered like a helicopter. In the present work the configuration of power electronics converters for the implementation of a 100kW AWT is considered. The major aspect here is the trade-off between power-to-weight ratio (W/kg) and efficiency. The dependence of cable weight and cable losses on the voltage level of power transmission is investigated, and a comparison made of low voltage (LV) and medium voltage (MV) versions of generators. Furthermore, the interdependence of the weight and efficiency of a bidirectional Dual Active Bridge dc-dc converter for coupling the rectified output voltage of a LV generator to the MV cable is discussed. Based on this, the concept offering the best possible compromise of weight and efficiency in the power electronics system is selected and a model of the control behavior is derived for both power flow directions. A control structure is then proposed and dimensioned. Furthermore, questions of electromagnetic compatibility and electrical safety are treated. In conclusion, the essential results of the work are summarized and an outlook on future research is given. To enable the reader to make simplified calculations and a comparison of a CWT with an AWT, the aerodynamic fundamentals of both systems are summarized in highly simplified form in an Appendix, and numerical values are given for the 100kW system discussed in this work.

In future applications, e.g. in ultra-flat OLED lamp drivers or flat screen power supplies, ultra-flat power systems are highly demanded. Therefore, the design and implementation of a PCB-integrated flyback transformer for a 1 mm thin PFC rectifier is under investigation. In this paper, an overview on several integration methods is given. It is shown that the PCB-integration of magnetic cores results in the required thickness of 1 mm and in a high energy density. Therefore, the design and the realization of ultra-flat magnetic components with PCB-integrated cores is detailed in this paper. The presented multi-objective design procedure determines the inductor and/or transformer setup optimal with respect to minimal losses and/or minimal footprint; for this purpose, the proposed design procedure considers all required electrical, magnetical, and geometrical parameters of the magnetic component. Furthermore, the design procedure accounts for anisotropic core loss behavior and includes an accurate reluctance model. Experimental results are used to verify the design procedure.

This scientific commentary refers to ‘Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia “CANVAS” syndrome’, by Wu et al. (doi: 10.1093/brain/awu196). A series of papers published in the 1990s by the Bronstein group triggered—albeit unintentionally—intensified research into a clinical syndrome characterized by a combination of selective bilateral vestibulopathy and cerebellar ataxia (Bronstein et al. , 1991; Waterston et al. , 1992; Rinne et al. , 1995). The term ‘cerebellar ataxia, neuropathy, vestibular areflexia syndrome’ (CANVAS) was subsequently coined in 2011 by Szmulewicz and colleagues, following a retrospective analysis of case records of patients with cerebellar ataxia and bilateral vestibulopathy with an impaired visually enhanced vestibulo-ocular reflex (Szmulewicz et al. , 2011). The latter reflects a combined failure of all three compensatory eye movement systems, and can be demonstrated clinically by turning a patient’s head slowly from side to side, with the test considered to be positive if compensatory eye movements are saccadic rather than smooth. Our understanding of CANVAS syndrome has improved over recent years and there have been numerous publications on specific symptoms. The existence of affected sibling pairs suggests …

In this paper, an innovative DC-DC converter is investigated which provides electrical power to the gate driver units of medium voltage level converters. For the discussed DC-DC converter, a galvanic isolation (isolation voltages of up to 35 kV) is required. This electrical isolation is achieved with a coreless transformer in order to obtain a cost-effective solution. Furthermore, the DC-DC converter contains a full-bridge converter being operated with low switching losses, a resonant compensation network to achieve a high overall efficiency and an output side rectifier. In this paper, the design of the coreless transformer, the appropriate compensation networks and the power electronics are discussed in detail. Moreover, measurement results obtained from a 100 W prototype, operated at a switching frequency of 410 kHz, are presented. With the proposed setup, a high overall efficiency of up to 80% and a transformer breakdown voltage of 55 kVrms is achieved. Thus, the proposed converter concept represents a very competitive solution with respect to the typically employed DC-DC converters with dry-type cast coil transformers.

The derivation of an accurate small-signal model for a galvanically isolated, bidirectional DC-DC converter and the implementation of a corresponding controller on a digital signal processor (DSP) as well as key methods and functions required for the digital implementation are detailed in this paper. The investigated DC-DC converter, an automotive Dual Active Bridge (DAB) system enables power transfer between a low voltage port (ranging from 11 V to 16 V) and a high voltage port (240 V to 450 V). The nominal power rating is 2 kW. The developed small-signal model yields highly accurate results for the DAB system, but the proposed modelling procedure could also be applied to arbitrary resonant power converters with unidirectional or bidirectional power transfer.

The main aim of this paper is to improve the performance of high current dual active bridge converters when operated over a wide voltage range. A typical application is for fuel cell vehicles where a bi-directional interface between a 12V battery and a high voltage DC bus is required. The battery side voltage ranges from 11V to 16V while the fuel cell is operated between 220V and 447V and the required power is typically 1kW. Careful analysis shows that the high currents on the battery side cause significant design issues in order to obtain a high efficiency. The standard phase shift modulation method can result in high conduction and switching losses. This paper proposes a combined triangular and trapezoidal modulation method to reduce losses over the wide operating range. Approximately, a 2% improvement in efficiency can be expected. An experimental system is used to verify the improved performance of the dual active bridge using the proposed advanced modulation method.

The working principles and design equations of four different isolated, bi-directional DC to DC converter topologies (a dual active bridge converter, a series resonant converter and two multiple stage topologies) for a 2 kW bi-directional battery charger that can be operated in a wide input and output voltage range are presented in this paper. The results of a detailed mathematical analysis of the converter topologies as well as digital simulation results are used to select the most efficient topology for this specific converter application, where the two-stage series resonant converter is identified to be the most promising, with up to 90% efficiency at rated power.

Background Increasing evidence suggests that olfaction is largely preserved in multiple system atrophy while most patients with Parkinson's disease are hyposmic. Consistent with these observations, recent experimental studies demonstrated olfactory deficits in transgenic Parkinson's disease mouse models, but corresponding data are lacking for MSA models. Methods Olfactory function and underlying neuropathological changes were investigated in a transgenic multiple system atrophy mouse model based on targeted oligodendroglial overexpression of α-synuclein as well as wild-type controls. The study was divided into (1) a pilot study investigating olfactory preference testing and (2) a long-term study characterizing changes in the olfactory bulb of aging transgenic multiple system atrophy mice. Results In our pilot behavioral study, we observed no significant differences in investigation time in the olfactory preference test comparing transgenic with wild-type animals. These findings were accompanied by unaffected tyrosine hydroxylase-positive cell numbers in the olfactory bulb. Similarly, although a significant age-related increase in the amount of α-synuclein within the olfactory bulb was detected in the long-term study, progressive degeneration of the olfactory bulb could not be verified. Conclusions Our experimental data show preserved olfaction in a transgenic multiple system atrophy mouse model despite α-synucleinopathy in the olfactory bulb. These findings are in line with the human disorder supporting the concept of a primary oligodendrogliopathy with variable neuronal involvement.

Similar to Parkinson disease, multiple system atrophy (MSA) presents neuropathologically with nigral neuronal loss; however, the hallmark intracellular α-synuclein (αSyn) accumulation in MSA affects typically oligodendrocytes to form glial cytoplasmic inclusions. The underlying pathogenic mechanisms remain unclear. As MSA is predominantly sporadic, epigenetic mechanisms may play a role. We tested the effects of the pan-histone deacetylase inhibitor (HDACi) sodium phenylbutyrate in aged mice overexpressing αSyn under the control of the proteolipid protein promoter (PLP–αSyn) designed to model MSA and characterized by αSyn accumulation in oligodendrocytes and nigral neurodegeneration. HDACi improved motor behavior and survival of nigral neurons in PLP–αSyn mice. Furthermore, HDACi reduced the density of oligodendroglial αSyn aggregates, which correlated with the survival of nigral neurons in PLP–αSyn mice. For the first time, we suggest a role of HDACi in the pathogenesis of MSA-like neurodegeneration and support the future development of selective HDACi for MSA therapy. Electronic supplementary material The online version of this article (doi:10.1007/s13311-016-0447-1) contains supplementary material, which is available to authorized users.