Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia.
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Animals↗
Biomedical subjects
W Poewe
Publications and source records attributed to W Poewe.
A relapsing-remitting type of ocular myasthenia gravis without typical muscle fatiguability.
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Adult↗
Modafinil for the treatment of daytime sleepiness in Parkinson's disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial.
OBJECTIVES: To assess the therapeutic efficacy of modafinil in the treatment of increased daytime sleepiness in patients with Parkinson's disease (PD). DESIGN: Double-blind, randomized, placebo-controlled crossover study with two 2-week treatment blocks, separated by a 2-week washout phase. SETTING: Tertiary Parkinson's disease care center and sleep laboratory at university hospital neurology department. PATIENTS: Fifteen patients with idiopathic PD and daytime sleepiness (Epworth sleepiness score (ESS) 10 or more). INTERVENTIONS: Administration of placebo or modafinil as a single morning dose in a randomized crossover order. The modafinil dose was 100 mg in the first, and 200 mg in the second treatment week. MEASUREMENTS AND RESULTS: At baseline and at the end of each treatment block, sleepiness was evaluated using subjective (perceived sleepiness with the ESS) and objective measures (maintenance of wakefulness test). Twelve patients completed the study (9 male, 3 female; mean age 65.0 +/- 7.6 years, mean disease duration 6.8 +/- 4.1 years). Epworth scores were significantly improved with modafinil (3.42 +/- 3.90) compared to placebo (0.83 +/- 1.99; p = 0.011). Latency to sleep in the maintenance of wakefulness test was not significantly altered by modafinil treatment: 10.9 (3-40)/15.1 (2.5-40) minutes before/after placebo and 12 (2.6-40)/17.8 (4.2-40) minutes before/after modafinil (p = 0.139) [data given as mean +/- standard deviation or median (range)]. CONCLUSIONS: The results of this study suggest that modafinil improves daytime sleepiness in PD patients, at least on a subjective or behavioral level. Modafinil treatment may be considered for EDS in PD patients, in whom otherwise treatable causes of Excessive Daytime Sleepiness (EDS) are absent.
Aged↗
Glial cell death induced by overexpression of alpha-synuclein.
alpha-Synuclein is present in intracellular protein aggregates that are hallmarks of common neurodegenerative disorders including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. alpha-Synuclein is localized in neurons and presynaptic terminals. Under pathological conditions, however, it is also found in glia. The role of alpha-synuclein in glial cells and its relevance to the molecular pathology of neurodegenerative diseases is presently unclear. To investigate the consequence of alpha-synuclein overexpression in glia, we transfected U373 astrocytoma cells with vectors encoding wild-type human alpha-synuclein or C-terminally truncated synuclein fused to red fluorescent protein. alpha-synuclein immunocytochemistry of transfected astroglial cells revealed diffuse cytoplasmic labeling associated with discrete inclusions both within cell bodies and processes. Susceptibility to oxidative stress was increased in astroglial cells overexpressing alpha-synuclein, particularly in the presence of cytoplasmic inclusions. Furthermore, overexpression of alpha-synuclein induced apoptotic death of astroglial cells as shown by TUNEL staining. Our in vitro model is the first to replicate salient features of the glial pathology associated with alpha-synucleinopathies. It provides a simple testbed to further explore the cascade of events that leads to apoptotic glial cell death in some of these disorders; it may also be useful to assess the effects of therapeutic interventions including antioxidative and antiapoptotic strategies.
Apoptosis↗
Cerebral ergotism under treatment with ergotamine and ritonavir.
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Adult↗
[Excessive daytime sleepiness: etiology, differential diagnosis and diagnostic procedures].
This article gives an overview on frequent causes of excessive daytime sleepiness in clinical practice. Specifically, the insufficient sleep syndrome, sleep disordered breathing, narcolepsy, restless legs syndrome/periodic limb movements in sleep, and circadian disorders causing daytime sleepiness are discussed. Other possible causes including symptomatic daytime sleepiness associated with various medical conditions are mentioned. Different methods to determine daytime sleepiness are discussed in the final section.
Diagnosis, Differential↗
Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study.
BACKGROUND: Chronic infections have been implicated in the pathogenesis of atherosclerosis, yet from an epidemiological perspective, this concept remains controversial. METHODS AND RESULTS: The Bruneck Study is a prospective population-based survey on the pathogenesis of atherosclerosis. In 826 men and women 40 to 79 years old (1990 baseline), 5-year changes in carotid atherosclerosis were thoroughly assessed by high-resolution duplex scanning. The presence of chronic respiratory, urinary tract, dental, and other infections was ascertained by standard diagnostic criteria. Chronic infections amplified the risk of atherosclerosis development in the carotid arteries. The association was most pronounced in subjects free of carotid atherosclerosis at baseline (age-/sex-adjusted odds ratio [95% CI] for any chronic infection versus none, 4.08 [2.42 to 6.85]; P:<0.0001) and applied to all types of chronic (bacterial) infections. It remained independently significant after adjustment for classic vascular risk attributes and extended to low-risk individuals free of conventional risk factors. Among subjects with chronic infections, atherosclerosis risk was highest in those with a prominent inflammatory response. Markers of systemic inflammation, such as soluble adhesion molecules and circulating bacterial endotoxin, and levels of soluble human heat-shock protein 60 and antibodies to mycobacterial heat-shock protein 65 were elevated in subjects with chronic infections and predictive of an increased risk of atherosclerosis. CONCLUSIONS: The present study provides solid evidence for a role of common chronic infections in human atherogenesis. Induction of systemic inflammation and autoimmunity may be potential pathophysiological links.
Adult↗
Progression of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders.
BACKGROUND: Dysarthria and dysphagia are known to occur in parkinsonian syndromes such as Parkinson disease (PD), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Differences in the evolution of these symptoms have not been studied systematically in postmortem-confirmed cases. OBJECTIVE: To study differences in the evolution of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. PATIENTS AND METHODS: Eighty-three pathologically confirmed cases (PD, n = 17; MSA, n = 15; DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis for a multicenter clinicopathological study organized by the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Cases with enough clinicopathological documentation for the purpose of the study were selected from research and neuropathological files of 7 medical centers in 4 countries (Austria, France, England, and the United States). RESULTS: Median dysarthria latencies were short in PSP and MSA (24 months each), intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months). Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months), and long in PD (130 months). Dysarthria or dysphagia within 1 year of disease onset was a distinguishing feature for atypical parkinsonian disorders (APDs) (specificity, 100%) but failed to further distinguish among the APDs. Survival time after onset of a complaint of dysphagia was similar in PD, MSA, and PSP (15 to 24 months, P =.7) and latency to a complaint of dysphagia was highly correlated with total survival time (rho = 0.88; P<.001) in all disorders. CONCLUSIONS: Latency to onset of dysarthria and dysphagia clearly differentiated PD from the APDs, but did not help distinguish different APDs. Survival after onset of dysphagia was similarly poor among all parkinsonian disorders. Evaluation and adequate treatment of patients with PD who complain of dysphagia might prevent or delay complications such as aspiration pneumonia, which in turn may improve quality of life and increase survival time.
Aged↗
The auditory startle reaction in parkinsonian disorders.
The auditory startle reaction to an unexpected loud stimulus is regarded as a brainstem reflex originating in the nucleus reticularis pontis caudalis and being distributed up the brainstem and down the spinal cord along slowly conducting pathways. Auditory startle responses (ASR) have been reported absent or reduced in progressive supranuclear palsy (PSP), and delayed in Parkinson's disease (PD), but normal in multiple-system atrophy (MSA). For the first time we studied ASR in patients fulfilling the clinical criteria of dementia with Lewy bodies (DLB) (n = 8), a neurodegenerative disorder characterized by cortical and subcortical depositions of Lewy bodies resulting in parkinsonism and progressive cognitive decline. For comparison, we also investigated patients with PD (n = 10), MSA (n = 7), PSP (n = 10), and age-matched healthy controls (n = 10). ASR were elicited by binaural high-intensity auditory stimuli. Surface electromyographic activity was simultaneously recorded from facial, upper, and lower extremity muscles. For each muscle, we assessed response probability and measured latency, amplitude, duration, and habituation rate. Patients with DLB had fewer and abnormally delayed ASR of low amplitude and short duration in extremity muscles compared to healthy controls. Furthermore, we confirm and extend previous findings of abnormal ASR in PSP and PD, and also demonstrate exaggerated ASR in extremity muscles of MSA patients. The different patterns of ASR abnormalities may reflect distinct types of brainstem dysfunction in DLB.
Acoustic Stimulation↗
Proton magnetic resonance spectroscopic imaging reveals differences in spinocerebellar ataxia types 2 and 6.
The objective of this study was to investigate cerebellar metabolism in patients with autosomal dominant cerebellar ataxia type 1 (ADCA-I) carrying two distinct mutations of spinocerebellar ataxia (SCA). Non-invasive image-guided proton magnetic resonance spectroscopy imaging (1H-MRSI) was performed in 4 patients with SCA2, and 3 patients carrying the SCA6 mutation. For MRSI, we employed a spin-echo sequence (TR = 1500 msec, TE = 135 msec, slice thickness = 15 mm, FOV = 240 mm) and a stimulated-echo sequence (TR = 1500 msec, TE = 20 msec, slice thickness = 15 mm, FOV = 240 mm). Measures included the peak integral ratios of neuronal and glial markers [N-acetylaspartate (NA) to creatine (Cr), choline-containing compounds (CHO) to Cr, and lactate (LAC) to Cr]. We found NA:Cr ratios were significantly lower in patients with SCA2 (40.4% lower) compared to patients carrying the SCA6 mutation. CHO:Cr ratios differed between the two mutations using short echo time (30.8% lower in SCA2), but not when applying long echo time 1H-MRSI. Measurements using long echo time revealed LAC peaks in all SCA2 patients. 1H-MRSI revealed metabolic differences between SCA2 and SCA6 patients. NA:Cr ratios were significantly lower in patients with the SCA2 mutation compared to the SCA6 mutation, and LAC signals were obtained in the cerebella of SCA2 patients. In addition, CHO:Cr ratios showed different behavior using short and long TE, indicating differences in relaxation times of choline compounds in SCA2.
Adult↗
Intrafamilial heterogeneity of facial hyperkinesias: chance association of tics, cranial dystonia, and Huntington's disease?
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Adult↗
Dynamic balance function in phasic cervical dystonia following Botulinum toxin therapy.
Previous research by our group revealed normal dynamic balance function in pure tonic cervical dystonia (CD) with impaired equilibrium in phasic CD patients investigated at least 3 months following Botulinum toxin (BtxA) treatment. The current study was performed to determine whether impaired dynamic equilibrium in phasic CD is influenced by symptomatic treatment with BtxA. Dynamic balance was tested in 20 patients with phasic CD on a dynamic platform with a cylindrical curved base (stabilometer) 4 weeks following BtxA treatment. Balance was assessed by the linear displacement of the platform and the maximum amplitude of platform displacement with open and closed eyes and compared with pre-BtxA data. Despite a clinically significant BtxA-induced reduction of phasic head movements, none of the platform measures improved significantly. In addition, there was no correlation between the BtxA-induced clinical improvement and changes in any of the dynamic balance measures pre- vs. post-BtxA. In conclusion, the persistent dynamic balance impairment after effective BtxA therapy may indicate that disequilibrium in phasic CD does not simply reflect disturbed vestibular input from repetitive head oscillations, but argues in favour of different sensorimotor processing in tonic and phasic CD.
Adult↗
Irresistible onset of sleep during acute levodopa challenge in a patient with multiple system atrophy (MSA): placebo-controlled, polysomnographic case report.
A 67-year-old male patient with clinically probable multiple system atrophy developed severe reproducible sleepiness and irresistible onset of sleep during an acute levodopa (L-dopa) challenge. In a placebo-controlled, double-blind study of acute L-dopa challenge, videopolysomnography revealed multiple episodes of non-rapid eye movement sleep 60 minutes after L-dopa and none following placebo. These observations suggest the irresistible sleep can also be induced by L-dopa and also in patients with atypical parkinsonism.
Aged↗
Treatment options for depression and psychosis in Parkinson's disease.
Neuropsychiatric symptoms are a frequent feature of advancing Parkinson's disease (PD). The reported prevalence of depression varies greatly between different studies but there is general consensus that between 40 and 50% of patients will be affected. Depression may antedate motor manifestations of Parkinson's disease and is usually of moderate or mild intensity. However, depression is of major impact on the quality of life in PD patients according to a recent survey. Drug-induced psychosis is one of the major therapeutic challenges in Parkinson's disease and may occur in up to 6% in otherwise uncomplicated de novo patients when first receiving dopaminergic therapy. It increases in frequency, in advanced disease and particularly in patients with dementia where up to 22% may be affected. There is an amazing lack of controlled clinical trials assessing the effects of antidepressants in clinical trials including more than 20 patients and assessing efficacy of antidepressants specifically in the context of mood changes in Parkinson's disease. A comprehensive literature search yielded only a total of 17 articles of which a majority included less than 20 patients and/or did not use valid depression ratings. The only randomized controlled trial was conducted more than 20 years ago using nortryptiline while no controlled trials were available on the use of serotonin reuptake inhibitors. Studies assessing the antidepressant action of dopaminergic therapies are few and inconclusive. Thus, while tricyclic antidepressants or SSRIs are widely used in clinical practice, there is still a need for controlled clinical trials proving their efficacy specifically in parkinsonian depression. Three randomized controlled trials are now available assessing the efficacy of the atypical neuroleptics clozapine and olanzapine in the treatment of drug-induced psychosis. While clozapine is of proven efficacy at least in the short-term management of this complication without negative impact on the motor symptoms, olanzapine in currently used doses of 2.5 to 15 mg/d seems to aggravate motor symptoms with lesser effect on psychosis compared to clozapine. Currently, clozapine is the atypical neuroleptic of choice for the treatment of drug-induced psychosis in Parkinson's disease.
Animals↗
Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease.
The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB. 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand 123I-beta-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS)-motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2 +/- 1.2, DLB 3.3 +/- 1, PD 4.2 +/- 1.4; means +/- SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4 +/- 0.4. 0.2 +/- 0.2 and 0.6 +/- 0.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2 +/- 12.7 vs 26.6 +/- 15.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2 +/- 2.3 vs 7.4 +/- 3.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.
Aged↗
Apoptosis signals in sporadic amyotrophic lateral sclerosis: an immunocytochemical study.
Sporadic amyotrophic lateral sclerosis (sALS) is a neurodegenerative disorder of unknown cause characterized by selective loss of both upper and lower motor neurons. Whether neuronal death in sALS is due to apoptosis has so far not been clarified. In this study, the expression and distribution patterns of pro- and anti-apoptotic bcl-2 family members as well as the executioner caspase-3 were investigated in post-mortem CNS tissue of eight sALS patients and seven age-matched controls. Sparse motor neurons were immunoreactive for bcl-2, bax, bak, and CM1 on serial sections through the spinal cord and motor cortex of individual sALS patients and controls. However, there was no obvious difference in the numbers of immunoreactive (IR) neurons between the two groups. The study did not find evidence for apoptosis as a major mechanism of motor neuronal cell death in sALS.
Aged↗
Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study.
Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.
Adolescent↗
Riluzole in Huntington's disease (HD): an open label study with one year follow up.
In an open label study, we administered riluzole (50 mg twice a day) to nine patients with genetically confirmed Huntington's disease (HD) (clinical stages 1-3; mean age 46.4 (SD 9.3) years; mean disease duration 8 (SD 3.3) years). The study was designed to evaluate (1) safety and tolerability of riluzole and (2) effects of riluzole on motor impairment, functional disability, cognitive impairment, and behavioral abnormalities using the Unified HD Rating Scale. Patients were evaluated at baseline and after three and twelve months of riluzole therapy. Laboratory tests (hematology and liver enzymes) were repeated monthly. All adverse experiences, reported spontaneously or observed directly by the investigator, were recorded. Riluzole was well tolerated. No increase of serum liver enzymes was seen throughout the study in all but one patient showing a mild elevation. At three months, mean total motor scale (TMS), mean TMS chorea subscore, and mean total functional capacity scale were significantly improved compared with baseline. At twelve months, however, this beneficial effect on motor status and overall function was not sustained. In contrast, severity and frequency of behavioral dysfunction as well as psychomotor speed assessed by the symbol digit modalities test were improved compared with baseline. Our data suggest that there are transient antichoreatic effects and more sustained effects of riluzole on psychomotor speed and behavior in patients with HD. A double-blind, placebo-controlled trial appears highly warranted to establish definitely the symptomatic versus neuroprotective actions of riluzole in HD.
Administration, Oral↗