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Sleep disorders, daytime sleepiness, and autonomic dysfunction are commonly reported among patients with multiple system atrophy and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness, and autonomic function.Twenty patients with multiple system atrophy (n = 7) and PD (n = 13) underwent clinical assessment including questionnaires for autonomic function and sleep. Cardiovascular autonomic function tests and 2-night video-polysomnography were followed by administration of the Multiple Sleep Latency Test. Rapid eye movement sleep without atonia was quantified in the chin, flexor digitorum superficialis, tibial anterior, and sternocleidomastoid muscles.Rapid eye movement sleep behavior disorder was associated with orthostatic hypotension (The relationship of autonomic dysfunction with rapid eye movement sleep without atonia in PD and multiple system atrophy is accounted for by shared brainstem neuropathology and likely identifies patients in a more advanced stage of disease. Excessive daytime sleepiness is found exclusively in PD and may be secondary to levodopa treatment and not related to α-synuclein disease.Eckhardt C, Fanciulli A, Högl B, et al. Analysis of sleep, daytime sleepiness, and autonomic function and multiple system atrophy and Parkinson disease: a prospective study.

Background Urological dysfunction in patients with multiple system atrophy (MSA) is one of the main manifestations of autonomic failure. Urodynamic examination is clinically relevant since underlying pathophysiology of lower urinary tract (LUT) dysfunction can be variable. Objective Evaluation of the pathophysiology of urological symptoms and exploration of differences in urodynamic patterns of LUT dysfunction between MSA‐P and MSA‐C. Methods Retrospective study of patients with possible and probable MSA who were referred for urodynamic studies between 2004 and 2019. Demographic data, medical history, physical examination and urodynamic studies assessing storage and voiding dysfunction were obtained. Results Seventy‐four patients were included in this study (MSA‐P 64.9% n = 48; median age 62.5 (IQR 56.8–70) years). Detrusor overactivity during filling phase was noted in 58.1% (n = 43) of the patients. In the voiding phase, detrusor sphincter dyssynergia and detrusor underactivity were observed in 24.6% (n = 17) and in 62.1% (n = 41) of the patients, respectively. A postmicturition residual volume of over 100 ml was present in 71.4% (n = 50) of the patients. Comparison of MSA subtypes showed weaker detrusor contractility in MSA‐P compared to MSA‐C [pdetQmax 26.2 vs. 34.4 cmH20, P = 0.04]. In 56.2% (n = 41) of patients pathophysiology of LUT dysfunction was deemed to be neurogenic and consistent with the diagnosis of MSA. In 35.6% (n = 26) urodynamic pattern suggested other urological co‐morbidities. Conclusion Urodynamic evaluation is an important tool to analyze the pattern of LUT dysfunction in MSA. Impaired detrusor contractility was seen more in MSA‐P which needs to be investigated in further studies.

Background The long-term impact of deep brain stimulation (DBS) on Parkinson's disease (PD) is difficult to assess and has not yet been rigorously evaluated in comparison to its natural history. Objective Comparison of key disability milestones (recurrent falls, psychosis, dementia, and institutionalization) and death in patients with PD with versus without DBS. Methods We collected retrospective information from clinical notes of patients with PD at our center that were implanted with subthalamic DBS >8 years ago (1999-2010) and a control group of PD patients without DBS similar in age at onset, age at baseline, sex distribution, and number of comorbidities at baseline (extracted from a registry study performed in 2004). Cox regression models were used to calculate hazard ratios, adjusted for potential baseline confounding variables (age, sex, disease duration, disease severity, and number of comorbidities). Results A total of 74 DBS-treated and 61 control patients with PD were included. For a median observational period of 14 years, patients treated with DBS were at lower risk of experiencing recurrent falls (hazard ratio = 0.57; 95% confidence interval, 0.37-0.90; P = 0.015) and psychosis (hazard ratio = 0.26; 95% confidence interval, 0.12-0.59; P = 0.001) compared with control patients. There was no significant difference in risk for dementia, institutionalization, or death. Disease progression as assessed by Hoehn and Yahr scores was not slower in DBS-treated patients. Conclusions Treatment with chronic subthalamic DBS was associated with lower risk for recurrent falls and psychotic symptoms, effects that may be mediated through improved motor symptom control and reduction in dopaminergic therapies, respectively. There was no evidence for DBS effects on underlying disease progression.

Objective Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between‐group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition. Methods This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work‐up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD‐plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS‐D). Results The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P

Purpose The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson’s disease and multiple system atrophy. Methods A prospective study including 19 Parkinson’s disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests. Results Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson’s disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson’s disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson’s disease patients (p Conclusions The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson’s disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson’s disease patients.

Iron is essential for cellular development and maintenance of multiple physiological processes in the central nervous system. The disturbance of its homeostasis leads to abnormal iron deposition in the brain and causes neurotoxicity via generation of free radicals and oxidative stress. Iron toxicity has been established in the pathogenesis of Parkinson's disease; however, its contribution to multiple system atrophy (MSA) remains elusive. MSA is characterized by cytoplasmic inclusions of misfolded α-synuclein (α-SYN) in oligodendrocytes referred to as glial cytoplasmic inclusions (GCIs). Remarkably, the oligodendrocytes possess high amounts of iron, which together with GCI pathology make a contribution toward MSA pathogenesis likely. Consistent with this observation, the GCI density is associated with neurodegeneration in central autonomic networks as well as olivopontocerebellar and striatonigral pathways. Iron converts native α-SYN into a β-sheet conformation and promotes its aggregation either directly or via increasing levels of oxidative stress. Interestingly, α-SYN possesses ferrireductase activity and α-SYN expression underlies iron mediated translational control via RNA stem loop structures. Despite a correlation between progressive putaminal atrophy and iron accumulation as well as clinical decline, it remains unclear whether pathologic iron accumulation in MSA is a secondary event in the cascade of neuronal degeneration rather than a primary cause. This review summarizes the current knowledge of iron in MSA and gives evidence for perturbed iron homeostasis as a potential pathogenic factor in MSA-associated neurodegeneration.

Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced hypotension are common features of cardiovascular autonomic failure. Despite the serious impact on patient's quality of life, evidence-based guidelines for non-pharmacological and pharmacological management are lacking at present. Here, we provide a systematic review of the literature on therapeutic options for neurogenic orthostatic hypotension and related symptoms with evidence-based recommendations according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Patient's education and non-pharmacological measures remain essential, with strong recommendation for use of abdominal binders. Based on quality of evidence and safety issues, midodrine and droxidopa reach a strong recommendation level for pharmacological treatment of neurogenic orthostatic hypotension. In selected cases, a range of alternative agents can be considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation strength is weak and quality of evidence is low (atomoxetine, octreotide) or very low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin). In case of severe postprandial hypotension, acarbose and octreotide are recommended (strong recommendation, moderate level of evidence). Alternatively, voglibose or caffeine, for which a weak recommendation is available, may be useful.

Eine orthostatische Hypotension, die im Rahmen von neurologischen Erkrankungen auftreten kann und mit einem kardiovaskularen Versagen vergesellschaftet ist, fuhrt zu einer erheblichen Beeintrachtigung der Lebensqualitat des Patienten. Ein adaquates Management ist daher von besonderer Relevanz.

Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative diseases with a variable clinical presentation that may even mimic Parkinson's disease. Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are commonly summarized under this umbrella term. Significant developments in research have expanded knowledge and have broadened available symptomatic treatments, particularly for the treatment of neurogenic orthostatic hypotension. Nonetheless, symptomatic support still remains limited in all of these disorders. Currently, there exists no effective treatment to delay disease progression and disease-modifying trials have failed to provide coherent and convincing results. Recent trials of rasagiline (in MSA), rifampicin (in MSA), tideglusib (in PSP) and davunetide (in PSP) reported negative results. Nevertheless, large cohorts of patients were recruited for interventional studies in the last few years which improved our understanding of trial methodology in APDs immensely. In addition, remarkable progress in basic research has been reported recently and will provide a solid foundation for future therapeutic trials. In this review, we will summarize published randomized, placebo-controlled clinical trials (RCTs) in APDs. Additionally, the design of ongoing and unpublished interventions will be presented.

Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced hypotension are common features of cardiovascular autonomic failure. Despite the serious impact on patient’s quality of life, evidence-based guidelines for non-pharmacological and pharmacological management are lacking at present. Here, we provide a systematic review of the literature on therapeutic options for neurogenic orthostatic hypotension and related symptoms with evidence-based recommendations according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Patient’s education and non-pharmacological measures remain essential, with strong recommendation for use of abdominal binders. Based on quality of evidence and safety issues, midodrine and droxidopa reach a strong recommendation level for pharmacological treatment of neurogenic orthostatic hypotension. In selected cases, a range of alternative agents can be considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation strength is weak and quality of evidence is low (atomoxetine, octreotide) or very low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin). In case of severe postprandial hypotension, acarbose and octreotide are recommended (strong recommendation, moderate level of evidence). Alternatively, voglibose or caffeine, for which a weak recommendation is available, may be useful.

Urinary function consists of a “storage” phase, in which tonic activation of urethral sphincter muscle occurs and bladder detrusor muscle is inhibited, and a “voiding” phase, in which detrusor activation and sphincter relaxation favor passing of urine. Both are under voluntary and involuntary neural control. Disorders of neural control of urinary function are also known as “neurogenic bladder” or “neurogenic lower urinary tract dysfunction.” Four main clinical pathological patterns can be distinguished at examination, with different therapeutic implications [27]: 1. Bladder detrusor overactivity: bladder storage capacity is reduced, but no or only low urine post-void volume occurs. 2. Detrusor sphincter dyssynergia: bladder storage capacity is reduced. Lack of coordination between bladder detrusor activation and urethral sphincter relaxation additionally induces post-void residual urine. 3. Hypoactive bladder: bladder capacity is increased. Insufficient detrusor activation leads to high post-void residual urine. 4. Hypoactive sphincter: bladder storage capacity is reduced, with no post-void residual urine.