Restless legs syndrome in Parkinson's disease.

We aimed to investigate the prevalence of restless legs syndrome (RLS) according to essential diagnostic criteria, and to explore potential associations with clinical features, especially motor fluctuations, in a cohort of 113 patients with idiopathic Parkinson's disease (PD). Twenty-eight (24%) fulfilled essential diagnostic criteria for RLS. They were younger (63.

Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure.

Objective: To report preliminary results of a prospective ongoing study of multiple system atrophy (MSA) and Parkinson disease (PD), with a large subset of patients with PD with autonomic failure (25%), to evaluate autonomic indices that distinguish MSA from PD.

Methods: We used consensus criteria, detailed autonomic studies (Composite Autonomic Symptom Scale, Composite Autonomic Scoring Scale, thermoregulatory sweat test, and plasma catecholamines), and functional scales (Unified MSA Rating Scale [UMSARS] I-IV and Hoehn-Yahr grading) on a prospective, repeated, and ongoing basis.

Results: We report the results of a study on 52 patients with MSA (mean [SD], age, 61.

SNCA variants are associated with increased risk for multiple system atrophy.

To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.

Recent developments in multiple system atrophy.

Multiple system atrophy (MSA) is a rare late onset neurodegenerative disorder which presents with autonomic failure and a complicated motor syndrome including atypical parkinsonism, ataxia and pyramidal signs. MSA is a glial alpha-synucleinopathy with rapid progression and currently poor therapeutic management. This paper reviews the clinical features, natural history and novel diagnostic criteria for MSA as well as contemporary knowledge on pathogenesis based on evidence from neuropathological studies and experimental models.

Striatal transplantation for multiple system atrophy--are grafts affected by alpha-synucleinopathy?

Multiple system atrophy (MSA), a fatal neurodegenerative disorder, is the second most common cause of parkinsonism and frequently associated with autonomic failure. Previous work from our laboratory has shown that striatal grafts survive and exert functional effects in toxin-induced rodent models of MSA-P, the parkinson variant characterized by levodopa resistance due to loss of striatal medium-sized spiny neurons. It is unknown whether oligodendroglial alpha-synuclein signature lesions affect graft survival in MSA.

Mitochondrial inhibitor 3-nitroproprionic acid enhances oxidative modification of alpha-synuclein in a transgenic mouse model of multiple system atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by autonomic failure, parkinsonism, cerebellar ataxia, and oligodendrocytic accumulation of alpha-synuclein (alphasyn). Oxidative stress has been linked to neuronal death in MSA and the mitochondrial toxin 3-nitropropionic acid (3NP) is known to enhance the motor deficits and neurodegeneration in transgenic mice models of MSA. However, the effect of 3NP administration on alphasyn itself has not been studied.

Mortality in Parkinson's disease: a 20-year follow-up study.

We determined mortality rates and predictors of survival in 238 consecutive patients with Parkinson's disease (PD) with symptom onset between 1974 and 1984. All patients were regularly followed at the Movement Disorder Clinic (Department of Neurology at the Innsbruck Medical University) until December 31, 2004, or death. As of December 31, 2004, 189 patients had died.

Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy.

Background: Two cerebrospinal fluid (CSF) biomarkers specific for neurodegeneration have recently emerged - the neurofilament light (NfL, 68 kDa) and heavy (NfH, 190-210 kDa) chains. This study investigated whether the CSF NfH and NfL levels or their stoichiometric relationship changed over time in a neuroprotective treatment trial.

Methods: Serial CSF samples (n=95) from 42 patients with multiple system atrophy (MSA), half randomized to treatment with recombinant human growth hormone (r-hGH) and the other half to placebo, were collected at baseline, 6 and 12 months.

Striatal transplantation in a rodent model of multiple system atrophy: effects on L-Dopa response.

Progressive degeneration of striatal projection neurons is thought to account for the loss of L-Dopa response observed in the majority of patients with the parkinsonian variant of multiple system atrophy (MSA-P). Here we have investigated the effects of E14 embryonic striatal allografts on dopaminergic responsiveness in the unilateral double-lesion rat model of MSA-P by using tests of complex motor behavior. Both sham and graft animals showed an increase in apomorphine-induced rotations as well as an improvement in cylinder test performance following surgical intervention.

Multiple system atrophy: a primary oligodendrogliopathy.

To this day, the cause of multiple system atrophy (MSA) remains stubbornly enigmatic. A growing body of observations regarding the clinical, morphological, and biochemical phenotypes of MSA has been published, but the interested student is still left without a clue as to its underlying cause. MSA has long been considered a rare cousin of Parkinson's disease and cerebellar degeneration; it is rich in acronyms but poor in genetic and environmental leads.

Red flags for multiple system atrophy.

The clinical diagnosis of multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA-P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as "red flags" or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA-P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA-SG) was administered to 57 patients with probable MSA-P and 116 patients with probable PD diagnosed according to established criteria.

Rasagiline is neuroprotective in a transgenic model of multiple system atrophy.

Rasagiline is a novel selective irreversible monoamine oxidase-B (MAO-B) inhibitor recently introduced for the symptomatic treatment of Parkinson disease. Like other propargylamines rasagiline has also shown neuroprotective effects independent of MAO-B-inhibition in various in vitro and in vivo models. The present study was performed to test the potential of rasagiline as a disease-modifying agent in multiple system atrophy (MSA) using a transgenic mouse model previously described by our group.

Survival in multiple system atrophy.

We here report survival in patients with multiple system atrophy (MSA) in a large, prospectively studied group of patients with MSA. Eighty-five of 100 patients were known to have died. Three patients were rediagnosed as having PD.

Predictors of survival in dementia with lewy bodies and Parkinson dementia.

Retrospective analysis of 243 autopsy-confirmed cases of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) showed an average age at symptom onset of 67 years and a median survival of 5 years from symptom onset. Older age at onset, fluctuating cognition, and hallucinations at onset predicted shorter survival; initial parkinsonism with delayed dementia significantly improved survival. Associated Alzheimer pathology also shortened survival.

Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy.

The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial alpha-synuclein inclusions and loss of midbrain dopaminergic neurons by means of histopathology and morphometric analysis. Our findings demonstrate early progressive microglial activation in substantia nigra pars compacta (SNc) associated with increased expression of iNOS and correlating with dopaminergic neuronal loss. Suppression of microglial activation by early long-term minocycline treatment protected dopaminergic SNc neurons.

Cerebrospinal fluid hypocretin-1 levels in multiple system atrophy.

Hypocretin (orexin) cerebrospinal fluid (CSF) levels have been previously found normal or decreased in Dementia with Lewy bodies and Parkinson disease, two synucleinopathies commonly associated with excessive daytime sleepiness (EDS). We evaluated CSF hypocretin-1 levels in 15 patients with moderately severe multiple system atrophy (MSA), another synucleinopathy where sleep disorders occur frequently and EDS has been reported, performing additional electrophysiological studies in 5 of them to assess the presence of EDS and sleep onset REM (SOREM) periods. Despite relatively low sleep efficiencies in nocturnal sleep, mean sleep latencies in the Multiple Sleep Latency Test were normal with no SOREM periods.

[Dementia with Lewy Bodies and its differentiation from Alzheimer's disease].

Dementia with Lewy Bodies (DLB) accounts for approximately 20 % of all autopsy-confirmed dementias in the elderly. Presumably, DLB is underdiagnosed in patients without or with only mild Parkinsonian symptoms in the daily routine of memory clinics. This motivated the Austrian Alzheimer Society and the Austrian Parkinson Society to inform about core features, suggestive features and supportive clinical findings of DLB and to provide information on diagnostic possibilities leading to better differential diagnosis.

Voxel based morphometry reveals specific gray matter changes in primary dystonia.

The present study assessed patterns of brain tissue alterations in different types of primary dystonia using voxel-based morphometry (VBM). Nine patients with primary generalized dystonia (GD), 11 patients with primary cervical dystonia (CD), and 11 patients with primary focal hand dystonia (FHD) as well as 31 age and gender-matched controls were included. When compared with healthy controls, patients with primary dystonia (n=31) showed gray matter volume increase bilaterally in the globus pallidus internus, nucleus accumbens, prefrontal cortex, as well as unilaterally in the left inferior parietal lobe.

Diffusion weighted imaging best discriminates PD from MSA-P: A comparison with tilt table testing and heart MIBG scintigraphy.

Both diffusion weighted magnetic resonance imaging (DWI) of the basal ganglia and meta-iodobenzylguanidin (MIBG) scintigraphy of the heart have been reported useful in the differential diagnosis of patients with Parkinson's disease (PD) vs. the parkinson variant of multiple system atrophy (MSA-P). Their diagnostic value, however, has never been directly compared in patients with parkinsonism and autonomic dysfunction.

An open trial of levetiracetam for segmental and generalized dystonia.

Local botulinum toxin injections represent the treatment of choice for most patients with focal dystonia. However, patients with segmental or generalized forms require additional pharmacologic treatment which is often ineffective or limited by intolerable side-effects. An animal study and three case reports suggested antidystonic effects of levetiracetam, a pyrrolidone derivate, whereas a recent open-label study found no improvement in 10 patients with primary idiopathic cervical dystonia.

Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study.

The objective of this study was to investigate tolerability and possible neurotrophic effects of growth hormone (GH) in treatment of multiple system atrophy (MSA). In this double-blind pilot study, MSA patients were randomized to recombinant human growth hormone (r-hGH, n = 22), 1 mg every second day (6 months) followed by alternating daily injections of 1 mg and 0.5 mg (6 months), or matched placebo (n = 21).

High dose levodopa therapy is not toxic in multiple system atrophy: experimental evidence.

Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors.