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Results for “Multiple System Atrophy”

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PubMed1997

Quantitative assessment of bradykinesia in patients with Parkinson's disease.

In order to optimize a method for quantitative assessment of bradykinesia, we evaluated the three-dimensional sources of a movement signal of the wrist and influence of tremor on the reliability of bradykinesia measurements. A total of 33 patients with Parkinson's disease, three patients with Multiple System Atrophy and 29 healthy controls performed a test procedure to measure slowness of movement, consisting of a tap rate (TR) test and a movement time (MT) test. Simultaneously, accelerometers were mounted on the wrist and mean bi- and tri-axial vectors were calculated. Thus the acquired means of acceleration were correlated with the commonly used measures of bradykinesia. i.e. tap rate and movement time. Our results show that bradykinesia is reliably measured by the evaluation of the mean acceleration of movements, and support the use of any of the three bi-axial vectors. Compared to the bi-axial vectors, the tri-axial vector provided no relevant additional information. Additionally, the presence of a moderate to severe resting tremor did not influence the assessment of bradykinesia. Because of the possibility of continuous assessment of bradykinesia this new monitor may prove to be of great value in pharmacodynamic studies and the longitudinal follow-up of patients in drug trials.

Aged↗

PubMedDate not supplied

Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice.

Alpha-synuclein is a major component of Lewy bodies (LBs) in the substantia nigra and cortex in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and in glial inclusions in multiple systems atrophy (MSA). Mutations in alpha-synuclein have been associated with autosomal dominant forms of PD. We investigated the clinical and neuropathological effects of overexpression of human alpha-synuclein, alpha-synuclein A30P, and alpha-synuclein A53T under the control of the hamster prion protein (PrP) promoter; 5-15x endogenous levels of protein expression were achieved with widespread neuronal, including nigral, transgene expression. High expression of alpha-synuclein A30P in the Tg5093 line was associated with a progressive motor disorder with rigidity, dystonia, gait impairment, and tremor. Histological analysis of this line showed aberrant expression of the protein in cell soma and progressive CNS gliosis, but no discrete Lewy body-like alpha-synuclein inclusions could be identified. Biochemical analysis demonstrated alpha-synuclein fragmentation. Despite strong expression of the transgene in the nigra, there was no specific deterioration of the nigrostriatal dopaminergic system as assessed by quantitation of nigral tyrosine hydroxylase (TH) containing neurons, striatal TH immunoreactivity, dopamine levels, or dopamine receptor number and function. Lower expressing lines had no specific behavioral or histopathological phenotype. Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line.

Animals↗

PubMed2003

Levodopa-induced oromandibular dystonia in progressive supranuclear palsy.

Levodopa-induced dyskinesias have been reported in Parkinson's disease and multiple system atrophy. Cranial dystonias are rare in patients with progressive supranuclear palsy (PSP). In this report we describe an unusual case of reversible levodopa-induced Oromandibular dystonia (OMD) in a PSP patient to highlight the importance of recognizing this drug related complication in the management of PSP, and discuss the possible underlying pathophysiology.

Aged↗

PubMed2004

Midkine and pleiotrophin in neural development and cancer.

The midkine (MK) family consists of only two members, namely heparin-binding growth factors MK and pleiotrophin (PTN). During embryogenesis, MK is highly expressed in the mid-gestational period, whereas PTN expression reaches the maximum level around birth. Both proteins are localized in the radial glial processes of the embryonic brain, along which neural stem cells migrate and differentiate. Zebrafish and Xenopus MK can induce neural tissues. In addition, deposits of MK and/or PTN are found in neurodegenerative diseases, such as Alzheimer's disease and multiple system atrophy. Both molecules are induced in reactive astrocytes by ischemic insults. In this context, it is interesting that LDL receptor-related protein is a receptor for MK and PTN, and this receptor has been implicated in the pathogenesis of Alzheimer's disease. MK and PTN share receptors, and show similar biological activities that include fibrinolytic, anti-apoptotic, mitogenic, transforming, angiogenic, and chemotactic ones. These activities explain how these molecules are involved in carcinogenesis. MK is detected in human carcinoma specimens from pre-cancerous stages to advanced stages. Strong expression of PTN is also detected in several carcinomas, although, in general, MK is expressed more intensely and in a wide range of carcinomas than PTN. The blood MK level is frequently elevated in advanced human carcinomas, decreases after surgical removal of the tumors, and is correlated with prognostic factors. Thus, it is a good market for evaluating the progress of carcinomas. Furthermore, antisense oligonucleotides for MK and ribozymes for PTN show anti-tumor activity. Therefore, MK and PTN are candidate molecular targets for therapy for human carcinomas.

Animals↗

PubMed2002

Ultrastructure of alpha-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells.

Abnormal alpha-synuclein-positive glial cytoplasmic inclusions are found in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. We have recently developed an in vitro model of alpha-synuclein-immunoreactive aggregations in U373 astrocytoma cells. We have additionally overexpressed wild-type and a C-terminally truncated form of alpha-synuclein in primary rat glial cells. Astrocytes and oligodendrocytes were found to form alpha-synuclein-positive aggregations in vitro perinuclearly or in the processes of the cells. The morphological studies presented here demonstrate that the aggregations we have observed in vitro are not limited by a membrane but have unclear borders. They have an amorphous dense core that is intensely alpha-synuclein-immunopositive and a predominantly filamentous halo around. Mainly filamentous structures at the border area between the halo and the core are alpha-synuclein-immunoreactive. We conclude that this in vitro model of alpha-synuclein-positive glial aggregations mimics the morphology of the abnormal glial inclusions described in neurodegenerative disorders and could be a suitable model for studying their role in the pathogenesis of these diseases.

Animals↗

PubMed2002

The prion protein in human neurodegenerative disorders.

We evaluate cellular prion protein (PrP(C)) immunoreactivity (IR) in Alzheimer's, Parkinson's, diffuse Lewy body, and motor neuron diseases (MND), progressive supranuclear palsy, and multiple system atrophy. We use immunohistochemistry for PrP, including five monoclonal antibodies against different epitopes and three different pretreatments, alpha-synuclein, phosphorylated tau, beta-amyloid, and ubiquitin. Disease-specific inclusions are devoid of PrP(C) IR. Using double immunofluorescence and confocal laser microscopy we observe focal overlapping of PrP(C) with tau and with alpha-synuclein in early, but not in fully developed inclusions. However, PrP(C) IR neurons may contain abnormal tau or alpha-synuclein aggregates. Additionally, we observe a loss of PrP(C) IR in anterior horn neurons in MND. Our results suggest that expression of PrP(C) reflects a general response to cellular stress rather than specific co-operation in aggregation of other proteins.

Amyloid beta-Peptides↗

PubMed1999

An endogenous MPTP-like dopaminergic neurotoxin, N-methyl(R)salsolinol, in the cerebrospinal fluid decreases with progression of Parkinson's disease.

There have been an increasing number of evidences indicating that dopamine-derived N-methyl(R)salsolinol is an endogenous MPTP-like neurotoxin to cause Parkinson's disease. In the cerebrospinal fluid from newly diagnosed untreated patients with Parkinson's disease, the level of this toxin was found to increase significantly, compared to control and a disease control, multiple system atrophy. The effects of the disease duration and the medication on the level of N-methyl(R)salsolinol were studied from the same patients. After about a 2-year period, the level was significantly reduced. The depletion of dopamine neurons by the disease progression may account for the reduction of the neurotoxin level, whereas L-DOPA therapy did not seem to affect the level of this toxin, even though the enhanced dopamine turnover. The results suggest that N-methyl(R)salsolinol level in the cerebrospinal fluid may indicate remaining dopamine neurons in the parkinsonian brain.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1997

Effects of alpha-phenyl-tert-butyl nitrone on neuronal survival and motor function following intrastriatal injections of quinolinate or 3-nitropropionic acid.

We have investigated the neuroprotective effects of the the spin-trapping agent alpha-phenyl-tert-butyl nitrone on striatal lesions produced by local injections of the excitotoxin quinolinate or the mitochondrial toxin 3-nitropropionic acid. We have assessed both the behavioural and morphological consequences of the lesion. Thus, we tested paw-reaching ability and amphetamine- and apomorphine-induced rotational behaviour in lesioned rats with or without alpha-phenyl-tert-butyl nitrone treatment, and also explored the relationship between the outcome of the behavioural studies and the extent of the lesion. In the morphological analysis, we chose immunocytochemistry for dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32,000 as a specific marker for striatal neurons. The paw-reaching ability of rats with the quinolinate and 3-nitropropionic acid lesions was significantly impaired compared to normal control animals. Treatment with alpha-phenyl-tert-butyl nitrone significantly ameliorated the paw-reaching deficits produced by the quinolinate lesion, whereas the 3-nitropropionic acid-induced deficits were unaffected by alpha-phenyl-tert-butyl nitrone. Both quinolinate and 3-nitropropionic acid lesions resulted in a rotation asymmetry towards the lesioned side in response to both amphetamine and apomorphine. In the quinolinate lesion model, the alpha-phenyl-tert-butyl nitrone treatment resulted in a less marked motor asymmetry in response to both drugs. By contrast, alpha-phenyl-tert-butyl nitrone did not significantly reduce the drug-induced rotation asymmetry in rats with a 3-nitropropionic acid lesion. Morphological analyses disclosed that alpha-phenyl-tert-butyl nitrone significantly increased the size of the spared striatum in the quinolinate lesions, but only caused a non-significant trend towards an attenuation of the 3-nitropropionic acid lesions. The behavioural deficits were inversely correlated to the size of the spared residual striatum. The intrastriatal injection of 3-nitropropionic acid, unlike the injection of quinolinate, caused degeneration of the nigrostriatal dopamine system as well as of transverse fibre bundles of the internal capsule in the striatum, in addition to the striatal lesion. The behavioural studies revealed that the combination of multiple lesions seen in 3-nitropropionic acid-lesioned rats significantly exacerbated paw-reaching deficits and amphetamine-induced rotation asymmetry. In conclusion, alpha-phenyl-tert-butyl nitrone attenuated behavioural and morphological consequences of striatal lesions induced by local injections of quinolinate, but not of 3-nitropropionic acid. Deficits in behavioural tests of striatal function reflected well the extent of striatal lesion. The intrastriatal injection of 3-nitropropionic acid led to degeneration of both intrinsic striatal neurons and the nigrostriatal dopaminergic system, suggesting that this lesion may provide an animal model of a form of multiple system atrophy rather than Huntington's disease.

Amphetamine↗

PubMed2000

Proton magnetic resonance spectroscopy of patients with parkinsonism.

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson's disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ((1)H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. (1)H-MRS may be useful in monitoring patients with various types of parkinsonism.

Aged↗

PubMed2002

Hypertension in orthostatic hypotension and autonomic dysfunction.

Disabling orthostatic hypotension dominates the clinical picture of autonomic failure. Nonetheless, severe supine hypertension is observed in about 50% of patients. In patients with multiple system atrophy (Shy-Drager syndrome), supine hypertension is explained by residual sympathetic tone because it can be eliminated with the ganglionic blocker trimethaphan. The cause of hypertension in patients with pure autonomic failure is not known and its understanding may be relevant to essential hypertension. Supine hypertension complicates the treatment of these patients but can be managed by overnight administration of antihypertensive medications.

Humans↗

PubMed1998

Filamentous nerve cell inclusions in neurodegenerative diseases.

Recent work has shown that abnormal filamentous inclusions within some nerve cells is a characteristic shared by Alzheimer's disease, some frontotemporal dementias, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, as well as Huntington's disease and other trinucleotide repeat disorders. This suggests that in each of these disorders, the affected nerve cells degenerate as a result of these abnormal inclusions. Except for trinucleotide repeat disorders, the filaments involved have been shown to consist of either the microtubule-associated protein tau or alpha-synuclein. Over the past year, mutations in the genes for tau and alpha-synuclein have been identified as the genetic causes of some familial forms of frontotemporal dementia and Parkinson's disease, respectively. The discovery last year of neuronal intranuclear inclusions in Huntington's disease and other disorders with expanded glutamine repeats has suggested a unifying mechanism underlying the pathogenesis of this class of neurodegenerative diseases.

Humans↗

PubMed2000

Neurophysiological studies of thin myelinated (A delta) and unmyelinated (C) fibers: application to peripheral neuropathies.

Dysfunction of small fibers may appear in isolation or associated with large fiber lesions. In some acute neuropathies, such as pandysautonomia, small-fiber impairment is relatively pure but it may also appear in disorders with prominent somatic damage, such as Guillain-Barré syndrome, in which autonomic failure worsens the prognosis. At the present time, chronic idiopathic distal small-fiber neuropathy is diagnosed more frequently, and in some prevalent disorders, such as diabetic or amyloidotic polyneuropathies, small-fiber dysfunction is very noticeable. In pure autonomic failure, a peripheral autonomic failure exists, distinguishing it from multiple-system atrophy. Complex regional pain syndrome is a severe condition in which small fibers are responsible for disabling signs and symptoms, and only instrumental recordings lead to the proper treatment. Standard neurophysiological techniques evaluate large myelinated fibers exclusively. Small-fiber polyneuropathy has been considered as a type of somatic neuropathy, but thin myelinated and unmyelinated fibers are responsible not only for temperature and pain perception but also autonomic function. For instance, full autonomic evaluation is needed in some clinical situations such as autonomic failure in the elderly or orthostatic intolerance syndrome. To evaluate small-fiber impairment we need a battery of sensitive, reproducible, specific and noninvasive tests covering somatic and autonomic systems. In this review, we describe and analyze a number of neurophysiological techniques used to diagnose and characterize small-fiber dysfunction in humans. These include cardiovascular monitoring, sudomotor testing, pupillary responses and quantitative sensory tests, and also to some extent thermography and laser evoked potentials. The use of such techniques has proven useful not only for diagnosis, but also to guide adequate therapy and optimize follow-up.

Electrophysiology↗

PubMed2001

Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson's disease.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) provide the means to studying in vivo the neurochemical, hemodynamic or metabolic consequences of the degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD). The extent of striatal dopaminergic denervation can be quantified with radiotracers as [18F]FDopa for PET and [123I]tropanes for SPECT. There are other radiotracers such as [11C]Dopa and meta-tyrosines as well as PET tracers for uptake sites. Striatal uptake of [18F]FDopa and [123I]tropanes is markedly decreased in PD, more in the putamen than in the caudate nucleus, and inversely correlates with the severity of motor signs and with duration of disease. PET and SPECT make possible the assessment by noninvasive means of the changes in dopamine receptor density, the effect of neuronal transplants or neuroprotective treatments in PD patients, or the nigrostriatal dopaminergic function in at-risk subjects. Activation studies using cerebral blood flow and metabolism measurements during a motor task reveal an impaired ability to activate the supplementary motor area and dorsolateral prefrontal cortex in PD. This functional disability is reversed by the use of dopaminergic medication or by surgical treatment by pallidotomy or deep brain stimulation. The differential diagnosis between PD and multiple system atrophy, progressive supranuclear palsy or corticobasal degeneration is not yet clearly established by PET and SPECT, even though these syndromes have some particular neurochemical and metabolic profiles. On the other hand, PET and SPECT are useful for distinguishing PD from Dopa-responsive dystonia, or for assessing the integrity of the nigrostriatal dopaminergic pathway in atypical cases of postural tremor or iatrogenic parkinsonian syndromes.

Aging↗

PubMed2003

The role of positron emission tomography imaging in movement disorders.

PET imaging provides the means to study neurochemical, hemodynamic, or metabolic processes that underlie movement disorders in vivo. Because the extent of presynaptic nigrostriatal dopaminergic denervation can be quantified in PD even at an early or preclinical stage of the disease, PET imaging may allow the selection of at-risk subjects for neuroprotective intervention trials. These techniques may also provide markers to follow progression of disease or evaluate the effects of neurorestorative interventions in patients who have more advanced disease. PET is expected to play an increasing role in the selection of patients who have PD for deep brain stimulation. Dopaminergic studies may have a limited clinical role in the diagnosis of patients who have symptoms that suggestive of PD yet do not respond to typical dopaminergic drugs, such as patients who have vascular parkinsonism or ET with mild resting tremor who may have normal dopaminergic innervation. The differential diagnosis between PD and multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration is not yet clearly established by PET, but combined pre- and postsynaptic dopaminergic imaging may be able to distinguish early idiopathic PD from atypical parkinsonian disorders, in general. Huntington's chorea is characterized by more prominent striatal dopamine receptor loss, whereas nigrostriatal denervation is present to a lesser degree. Patients who have TS may have enhanced synaptic dopamine release in the putamen. Functional imaging studies have generally failed to demonstrate nigrostriatal denervation in essential tremor or idiopathic dystonia. Studies have shown striatal dopamine receptor loss in selected subtypes of dystonic patients. In conclusion, it is expected that PET will help us to better understand the pathophysiology of movement disorders, increase the diagnostic accuracy, allow preclinical diagnosis, monitor disease progression, and evaluate the efficacy of therapeutic agents. Pharmacologic radioligand displacement studies and the development of new nondopaminergic ligands may further aid in the unraveling of cerebral mechanisms that underlie movement disorders.

Brain↗

PubMed2000

Diagnosis and differential diagnosis of Parkinson's disease and parkinsonism.

In the clinic setting, most cases represent either Parkinson's disease (PD) or one of the other neurodegenerative disorders that make up the parkinsonism-plus syndromes. The major parkinsonism-plus syndromes include progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, as well as parkinsonism occurring in the context of Alzheimer's disease or one of the other primary dementing disorders. There are a variety of other conditions, however, that occasionally come into the differential diagnosis. These fall into the categories of secondary parkinsonism (due to drugs, toxins, structural lesions, etc.), another tremor syndrome such as essential tremor, or a hereditary disorder with parkinsonism. This broad differential diagnosis is reviewed.

Journal Article↗

PubMed2003

Myoclonus and neurodegenerative disease--what's in a name?

Myoclonus is a clinical symptom (or sign) defined as sudden, brief, shock-like, involuntary movements caused by muscular contractions or inhibitions. It may be classified by examination findings, etiology, or physiological characteristics. The main physiological categories for myocolonus are cortical, cortical-subcortical, subcortical, segmental, and peripheral. Neurodegenerative syndromes are potential causes of symptomatic myoclonus. Such syndromes include multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17, Huntington's disease, dentato-rubro-pallido-luysian atrophy, Alzheimer's disease, and Parkinson's disease, and other Lewy body disorders. Each neurodegenerative syndrome can have overlapping as well as distinctive clinical neurophysiological properties. However, claims of differentiating between neurodegenerative disorders by using the presence or absence of small amplitude distal action myclonus appear unwarranted. When the myoclonus is small and repetitive, it may not be possible to distinguish it from tremor by phenotypic appearance alone. In this case, clinical neurophysiological offers an opportunity to provide greater differentiation of the phenomenon. More study of the myoclonus in neurodegenerative disease will lead to a better understanding of the processes that cause phenotypic variability among these disorders.

Humans↗

PubMed2000

REM sleep behavior disorder.

REM sleep is the stage associated with vivid dream mentation, desynchronous cortical EEG, and atonia of antigravitary muscles. REM sleep behavior disorder (RBD) is characterized by the intermittent loss of REM sleep atonia and by the appearance of elaborate motor activity associated with dream mentation. The animal model of REM sleep without atonia indicates that lesions to the perilocus coeruleus disrupt the excitatory connection to the nucleus reticularis magnocellularis in the descending medullary reticular formation and disable the hyperpolarization of the alpha spinal motoneurons. Extensive neurologic evaluations in humans suffering from both idiopathic and symptomatic forms have not identified specific lesions; however, findings in some patients suggest that diffuse lesions of the hemispheres, bilateral thalamic abnormalities, or primary brain-stem lesions may result in the RBD. Symptomatic RBD cases are associated with several neurologic disorders such as dementia, cerebrovascular diseases, multiple sclerosis, brain-stem neoplasm. RBD has been often documented to precede or to co-occur with neurodegenerative disorders, such as dementia, Parkinson's disease and multiple system atrophy. Most importantly, RBD is readily diagnosable and treatable. Patients and their bed partners usually report immediate improvement in sleep-related motor behavior with small doses of clonazepam.

Brain↗

PubMed2003

Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients.

OBJECTIVE: To describe the treatment response with melatonin for rapid eye movement (REM) sleep behavior disorder (RBD) associated with other neurologic disorders. BACKGROUND: Clonazepam has been considered the treatment of choice for RBD. However, an alternative treatment is desirable for those with RBD refractory to clonazepam, for those who experience intolerable side-effects with clonazepam, and for those in whom clonazepam precipitates or aggravates obstructive sleep apnea (OSA). To date, there is minimal published data and limited follow-up regarding the use of melatonin for patients with RBD associated with other neurologic syndromes and disorders. DESIGN/METHODS: The response to melatonin treatment for RBD was reviewed on consecutive patients the investigators treated with this agent at Mayo Clinic Rochester from January 2000 to June 2001. The coexisting neurologic disorders, reasons for using melatonin, effective doses, side-effects, and duration of follow-up were also reviewed on all patients. RESULTS: Fourteen patients were commenced on melatonin over the specified time period (13 male, median RBD onset age 56 years, range 20-77 years). The coexisting neurologic findings/disorders were dementia with Lewy bodies (n=7), mild cognitive impairment with mild parkinsonism (n=2), multiple system atrophy (n=2), narcolepsy (n=2), and Parkinson's disease (n=1). The reasons for using melatonin in these cases were incomplete response of RBD to clonazepam in six patients, existing cognitive impairment in five, intolerable side-effects with clonazepam in two, and presence of severe obstructive sleep apnea and narcolepsy in one. With seven patients continuing to use clonazepam at 0.5-1.0 mg/night, RBD was controlled in six patients, significantly improved in four, and initially improved but subsequently returned in two; no improvement occurred in one patient and increased RBD frequency/severity occurred in one patient. The effective melatonin doses were 3 mg in two cases, 6 mg in seven cases, 9 mg in one case, and 12 mg in two cases. Five patients reported side-effects, which included morning headaches (2), morning sleepiness (2), and delusions/hallucinations (1); these symptoms resolved with decreased dosage. The mean duration of follow-up was 14 months (range 9-25 months), with eight patients experiencing continued benefit with melatonin beyond 12 months of therapy. CONCLUSIONS: In this series, persistent benefit with melatonin beyond 1 year of therapy occurred in most but not all patients. Melatonin can be considered as a possible sole or add-on therapy in select patients with RBD. Prospective, long-term, controlled trials with melatonin are warranted in a larger number of patients with RBD associated with a variety of neurologic symptoms and disorders.

Adult↗