Effects of long-term, continuous subcutaneous apomorphine infusions on motor complications in advanced Parkinson's disease.
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Antiparkinson Agents↗
Biomedical subjects
W Poewe
Publications and source records attributed to W Poewe.
123I-beta-CIT and 123I-IBZM-SPECT scanning in levodopa-naive Parkinson's disease.
Striatal dopamine transporter function and dopamine D2 receptor status were evaluated in 15 patients with early untreated Parkinson's disease using single photon emission tomography (SPECT) with 123I-Iodo-2beta-carboxymethoxy-3beta-(4-idiophenyl)tropane (beta-CIT) and 123I-Iodobenzamide (IBZM) as pre- and postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but asymmetric in 10 patients. Patients with bilateral symptoms had significantly lower 18-hour striatal/cerebellar beta-CIT binding ratios (3.59 +/- 0.79) than hemiparkinsonian patients (5.76 +/- 1.48, p < 0.05) reflecting more advanced disease in this subgroup. Patients with bilateral parkinsonism were also found to have a significant side-to-side difference in striatal beta-CIT binding with more marked reduction contralateral to the presenting limb (18-hour striatal/cerebellar ratio: 4.13 +/- 0.78 [ipsilateral] versus 3.59 +/- 0.79 [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was significantly elevated contralateral to the affected side in hemiparkinsonian patients (striatal/cerebellar ratio: 2.42 +/- 0.90 [contralateral] versus 2.19 +/- 0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 +/- 0.43 [contralateral to more severely affected side] versus 1.83 +/- 0.34 [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor upregulation contralateral to the presenting side occurs in untreated unilateral PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss of dopamine transporter function. Combined beta-CIT and IBZM SPECT studies may be helpful to monitor the progression of nigrostriatal dysfunction in early PD.
Aged↗
Cortical and brain stem hyperexcitability in striatonigral degeneration.
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Brain Stem↗
Dose standardization of botulinum toxin.
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Animals↗
Unilateral painful legs and moving toes syndrome with moving fingers--evidence for distinct oscillators.
This case report presents a patient with painful legs and moving toes on the right side followed by the development of involuntary movements in his right hand. The frequencies of the semirhythmic muscle activities in both extremities were different. This finding excludes one central pacemaker for both and supports the notion that separate oscillators in the segmental interneuron pool of different spinal areas may drive the individual movements in this case.
Electromyography↗
Cortical evoked potentials of the vesicourethral junction--a predictor for the outcome of intravesical electrostimulation in patients with sensory and motor detrusor dysfunction.
The evaluation of cortical evoked potentials after stimulation of the vesicourethral junction shows accurate and reproducible results and offers an elegant technique for evaluation of the viscerosensory pathways in patients with lower urinary tract dysfunction. The results must be considered in context with the results of simultaneously investigated pudendal somatosensory evoked potentials and the clinical symptomatology. They are of great help (1) in differentiating between intraspinal and extraspinal lesions of the afferent pathways of the detrusor if the etiology is unknown, (2) in differentiating between neurogenic and myogenic damage to the urinary bladder, and (3) in selecting patients not suitable for intravesical electrotherapy for bladder rehabilitation.
Adolescent↗
What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group.
OBJECTIVES: Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS: Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4, and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS: Seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p<0.05). Additionally positive dose-response relations were found for the degree of subjective improvement, duration of improvement, improvement on clinical global rating, and need for reinjection at eight weeks. A significant dose relation was also established for the number of adverse events overall and for the incidence of neck muscle weakness and voice changes. CONCLUSION: Magnitude and duration of improvement was greatest after injections of 1000 units Dysport; however, at the cost of significantly more adverse events. Therefore a lower starting dose of 500 units Dysport is recommended in patients with cervical dystonia, with upward titration at subsequent injection sessions if clinically necessary.
Adult↗
Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination.
OBJECTIVE: To analyse the natural history and survival of corticobasal degeneration by investigating the clinical features of 14 cases confirmed by postmortem examination. METHODS: Patients with definite corticobasal degeneration were selected from the research and clinical files of seven tertiary medical centres in Austria, the United Kingdom, and the United States. Clinical features were analysed in detail. RESULTS: The sample consisted of eight female and six male patients; mean age at symptom onset was 63 (SD 7.7) years, and mean disease duration was 7.9 (SD 2.6) years. The most commonly reported symptom at onset included asymmetric limb clumsiness with or without rigidity (50%) or tremor (21%). At the first neurological visit, on average 3.0 (SD 1.9) years after symptom onset, the most often encountered extrapyramidal features included unilateral limb rigidity (79%) or bradykinesia (71%), postural imbalance (45%), and unilateral limb dystonia (43%). Ideomotor apraxia (64%), and to a lesser extent cortical dementia (36%), were the most common cortical signs present at the first visit. During the course of the disease, virtually all patients developed asymmetric or unilateral akinetic rigid parkinsonism and a gait disorder. No patient had a dramatic response to levodopa therapy. Median survival time after onset of symptoms was 7.9 (SD 0.7) (range, 2.5-12.5) years, and, after the first clinic visit, 4.9 (SD 0.7) (range, 0.8-10) years. Early bilateral bradykinesia, frontal syndrome, or two out of tremor, rigidity, and bradykinesia, predicted a shorter survival. CONCLUSION: The results confirm that unilateral parkinsonism unresponsive to levodopa and limb ideomotor apraxia are the clinical hallmarks of corticobasal degeneration, and only a minority of patients with corticobasal degeneration present with dementia. The study also suggests that a focal cognitive and extrapyramidal motor syndrome is indicative of corticobasal degeneration. Survival in corticobasal degeneration was shortened by the early presence of (more) widespread parkinsonian features or frontal lobe syndrome.
Aged↗
Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients.
BACKGROUND: More than 50% of patients with Parkinson's disease develop motor response fluctuations (the 'wearing off" phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients' clinical status, duration of improvements, and tolerability of tolcapone. METHODS: In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide. RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 26.2% of the baseline value, "on" time increased by 20.6% (p < 0.01 vs. placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (p < 0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (p < 0.05), "on" time increased by 21.3% (p < 0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (p < 0.05). With 200 mg tolcapone tid, unified Parkinson's disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhoea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhoea. CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy.
Aged↗
Adjuncts to levodopa therapy: dopamine agonists.
The classical role of dopamine agonists in Parkinson's disease (PD) therapy is adjunctive treatment to levodopa once "wearing-off" fluctuations or more malignant types of "on-off" swings have developed. Dopamine agonists reduce the frequency, severity, and duration of "off" periods while allowing the levodopa dose to be reduced. Interest is growing in the role of dopamine agonists as primary monotherapy in PD. Studies of early monotherapy have shown that, even with sustained treatment, drug-induced dyskinesias rarely develop. However, this approach is successful for more than 3 years in only about 30% of all PD patients. Continuous dopaminergic stimulation via subcutaneous dopamine agonist infusions is being investigated as a way to control levodopa-associated peak-dose dyskinesias. Early combined treatment with levodopa has been suggested as effective while avoiding long-term complications, but the therapy remains controversial. Despite the entry of several new dopamine agonists into clinical practice, the ideal agonist, with long duration of action and efficacy equal to that of levodopa, is still lacking. The clinical pharmacology of dopamine agonists is reviewed.
Antiparkinson Agents↗
Should treatment of Parkinson's disease be started with a dopamine agonist?
Which drugs to use when initiating pharmacotherapy in early Parkinson's disease (PD) is a complex treatment decision that depends on factors such as disease severity, functional disability, and psychosocial handicap, as well as individual aspects of age, employment status, cognitive impairment, and co-morbidity. Without clear proof of a drug's capacity to markedly alter or even stop progression of the disease, there is no pharmacologic strategy that can be currently viewed as universal first-line treatment. Dopamine (DA) replacement strategies offer greatest symptomatic relief and are needed whenever there is significant functional disability. All currently available oral DA agonists have been shown to be less effective and less well tolerated than levodopa. This has also been shown in recent double-blind controlled studies for the novel agonists such as ropinirole or cabergoline, although they appear equally effective in mild disease for the first 6-12 months of therapy. Taking into account the significant difference in cost between levodopa and DA agonists, there is at present no reason to universally start DA replacement therapy with a DA agonist in most patients. Dopamine agonists remain first-line treatment only for those at particular risk for developing levodopa-induced dyskinesias, i.e., young-onset PD patients.
Antiparkinson Agents↗
[Psychosomatic aspects of idiopathic spasmodic torticollis. Results of a multicenter study].
Idiopathic spasmodic torticollis (IST) is one of the most frequent dystonic movement disorders. Its classification as a focal dystonia, as well as its treatment with botulinum toxin resulted in groups of patients being regularly seen by neurologic specialists. In a multicentre study, we investigated psychosocial changes, coping and psychopathology, and their interrelations with signs, symptoms and course. 256 patients were included in the study (59.3% women, 40.7% men). The mean age was 49.1 years. Rotating torticollis occurred more often than latero-retrocollis and antero-retrocollis. A family history of IST was seen in 3.1% of the total sample. 34% of the patients had additional dystonic symptoms. Most frequently, these affected the upper extremities (13%), less often the legs. 19.1% of the patients had experienced a period of complete remission. The General Symptom Index of the SCL 90-R in 27% of the patients ranged above the double standard deviation of the normal controls, indicating a clinically significant psychopathology.
Adaptation, Psychological↗
Loss of dopamine-D2 receptor binding sites in Parkinsonian plus syndromes.
UNLABELLED: This study analyzed temporal changes of striatal dopamine-D2 receptor binding during the course of different extrapyramidal movement disorders using 123I-iodobenzamide (IBZM) SPECT. METHODS: Eighteen patients (9 with Parkinson's disease, 9 with parkinsonian plus syndrome) were followed for 11-53 mo. Dopamine-D2 receptor binding was assessed using 123I-IBZM SPECT at the beginning and at the end of the follow-up period. SPECT data were acquired 120 min postinjection of 3-5 mCi 123I-IBZM. A semiautomated algorithm was applied to the raw data for semiquantitative evaluation of regional cerebral receptor binding. RESULTS: Intraobserver (r = 0.992) and interobserver (r = 0.930) variance was low for the semiautomated interpretation of the SPECT examination of the dopaminergic D2 receptor binding, reflecting a highly reproducible SPECT algorithm. Mean specific dopamine-D2 receptor binding was lower in patients with parkinsonian plus syndrome compared to patients with Parkinson's disease on the initial (p < 0.001) as well as the follow-up study (p < 0.001). In patients with Parkinson's disease, we observed an unaffected receptor binding compared to a reduced binding of radiotracer in patients with parkinsonian plus syndrome during the course of the disease (p < 0.001). CONCLUSION: During the follow-up, patients with Parkinson's disease showed a constant dopamine-D2 receptor binding. In contrast, patients with parkinsonian plus syndrome revealed a decline of the binding of dopamine-D2 receptor. These findings are in agreement with histopathological data that demonstrated a preserved dopamine-D2 receptor status in patients with Parkinson's disease and a decline of the dopamine-D2 receptors in patients with parkinsonian plus syndrome. SPECT examinations using 123I-IBZM are useful for assessing dynamic changes of dopamine-D2 receptors in extrapyramidal movement disorders. Semiquantitative SPECT evaluations may provide valuable information for clinical management and prognosis of the patient with extrapyramidal movement disorders.
Adult↗
Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study.
BACKGROUND: Fe2+ released from tissue iron stores may accelerate lipid peroxidation by virtue of its pro-oxidant properties and thus promote early atherogenesis. METHODS AND RESULTS: The present prospective survey addresses the potential association between serum ferritin concentrations and the 5-year progression of carotid atherosclerosis as assessed by ultrasonographic follow-up evaluations. The study population comprises a random sample of 826 men and women 40 to 79 years old. Serum ferritin was one of the strongest risk predictors of overall progression of atherosclerosis. The main part of this association appeared to act through modification of the atherogenic potential of LDL cholesterol (OR [95% CI] for a 1-SD unit increase in ferritin at LDL levels of 2.5, 3.6, and 4.9 mmol/L: 1.55 [1.30 to 1.85], 1.77 [1.40 to 2.24], and 2.05 [1.50 to 2.80]; P=.0012 for effect modification). Changes in iron stores during the follow-up period modified atherosclerosis risk, in that a lowering was beneficial and further iron accumulation exerted unfavorable effects. All these findings applied equally to incident atherosclerosis and the extension of preexisting atherosclerotic lesions. The significance of prominent iron stores in the development of carotid stenosis was clearly less pronounced. Finally, ferritin and LDL cholesterol showed a synergistic association with incident cardiovascular disease and death (n=59). CONCLUSIONS: The present study provided strong epidemiological evidence for a role of iron stores in early atherogenesis and suggests promotion of lipid peroxidation as the main underlying pathomechanism. This hypothesis could in part explain the sex difference in atherosclerotic vascular disease.
Adult↗
Tardive jaw tremor.
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Anti-Dyskinesia Agents↗
Quantitative assessment of botulinum toxin treatment in 43 patients with head tremor.
We treated 43 patients who had head tremor as the major complaint with local botulinum toxin type A (Btx A) injections into neck muscles: 29 patients were classified as suffering from tremulous cervical dystonia (TCD), and 14 had head tremor without dystonia (HT). All patients were clinically assessed by means of the Tsui scale and a 4-point pain scale at baseline and follow-up visit. Quantitative recordings of head tremor with a bidirectional accelerometer system (horizontal and vertical planes) placed on the forehead were obtained before and 2-3 weeks after Btx A injections. Muscle selection for an injection was based on the visible and palpable tremor oscillation in the involved neck muscles and on analysis of standardized simultaneous electromyographic recordings of six cervical muscles. Patients with HT received mean total doses of 400 units (U) of Dysport (Btx A) (range, 160-560 U) distributed between the two splenius capitis muscles. Patients with TCD received a mean total dose of 500 U Dysport (range, 320-720 U) injected into a mean of 3 muscles (range, 2-4 muscles). The condition of all patients with HT and of 26 of the 29 patients with TCD improved subjectively. The total on the Tsui scale as well as pain scores decreased significantly (p < 0.05) following treatment. Latency of onset, duration of improvement, and side effects showed no significant difference in HT and TCD. Amplitude of HT decreased significantly for both groups following treatment. The mean dominant peak frequency in TCD and HT was slightly less than 5 Hz and did not change significantly after treatment.
Adult↗
A new tremor mutant in the Pietrain pig: an animal model of orthostatic tremor? Clinical and neurophysiological observations.
A new tremor mutant, the "Campus syndrome" was studied in a breed of Pietrain pigs. Affected pigs showed a coarse tremor of the extremities when standing and walking, so they tended to remain recumbent, during which the tremor was suppressed. Needle electromyographic recordings of the semitendinosus muscle plus accelerometry revealed a high-amplitude 14- to 15-Hz tremor pattern activated specifically upon standing but maintained during walking. The observed syndrome thus bears similarities to the human condition of orthostatic tremor and might serve as an animal model for this as yet poorly understood disorder.
Animals↗
Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.
Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.
Aged↗