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Biomedical subjects

W Poewe

Publications and source records attributed to W Poewe.

At least 163 records · Page 9Linked to original sources

Influence of concurrent tasks on gait: a dual-task approach.

We studied the effect of concurrent tasks on motor control of gait with dual-task methodology. Ten healthy subjects were instructed to perform different cognitive and motor tasks during gait on a conductive walkway. Footswitch signals were recorded and stride time and double-support time were calculated. It was assumed that the former reflects gait-patterning mechanisms and the latter relates to balance control. Statistical analysis showed an increase in double-support time when a memory-retention task (digit-span) and a fine motor task (buttoning) were executed simultaneously during gait. During gait performance of the cognitive task declined compared to baseline conditions. Attentional demand of concurrent cognitive and motor tasks appeared to force subjects to modulate their gait strategy to ensure control of balance. Stride time was consistent across task conditions except when subjects performed fast finger-tapping during gait. Then all but one subject showed a decrease in stride time and an increase in stride-frequency that was repeatable on retest. Since different rhythmic movements are likely to share common neurobiological networks, we assumed that the modulation of stride-frequency was due to structural interference.

Adult↗

[Clinical variants of pseudotumor cerebri syndrome].

Increased cerebrospinal fluid pressure of usually unknown etiology is called pseudotumor cerebri. The key symptoms are headache, papilledema and fluctuating visual disturbances. Six cases are presented to illustrate the clinical variability of this syndrome. Headache or papilledema may be missing in individual cases. The clinical diagnosis can be facilitated by the recognition of accessory signs and symptoms, such as VIth nerve palsy, tinnitus and other cranial nerve disorders or neck stiffness. For the therapeutic outcome it is essential to detect and monitor visual disturbances early in the course of the disease.

Adult↗

[Brain SPECT with 123I-lisuride in patients with Parkinson's disease and controls].

The goal was to visualize cerebral dopamine-D2 receptors in 6 patients with Parkinson's disease and in 3 healthy controls using iodine-123-Lisuride-SPECT. In addition, we performed receptor-replacement studies using 123I-Lisuride and cold Lisuride as competitive ligands. The highest uptake of 123I-Lisuride was observed in the striatum, a region with known high dopamine receptor density. In two patients premedication with cold Lisuride displaced 123I-Lisuride from the dopamine receptor. 123I-Lisuride is valuable as a radiotracer in cerebral dopamine-D2 receptor scintigraphy. Whether or not it is possible to determine dynamic changes of dopamine receptor density or function by receptor replacement studies needs further evaluation in larger patient populations.

Adult↗

[Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease].

In an open label study 63 patients with idiopathic Parkinson's disease suffering from end-of-dose akinesia were switched from a treatment with a L-DOPA standard formulation to a combined therapy of L-DOPA standard in the morning and L-DOPA slow release (levodopa, benserazide, Madopar Depot) at the remaining single doses. Substitution of L-DOPA standard by L-DOPA slow release took on average 2-4 weeks. Patients were subsequently treated for 6 months. Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy. In 20 centers 37 men and 26 women were included into the study. 27 males and 20 females completed the 6 month treatment period. Before switching, the patients received 438 +/- 213 mg a day L-DOPA standard, after conversion, the average dose was 617 +/- 323 mg L-DOPA slow release and 107 +/- 95 mg L-DOPA standard a day. Fluctuations during the day and at night which were rated according to a newly developed clinical 5-point rating scale were significantly improved by the treatment regimen from 2.8 +/- 0.9 to 1.4 +/- 1.2. Additionally, parkinsonian symptoms were significantly reduced during the ON-phase as there was a significant decrease of the Webster rating score from 12.0 +/- 4.6 to 7.1 +/- 4.0. Quality of life as measured by subjective ratings of the patients improved. The tolerability of the new formulation of L-DOPA was rated to be good in 51.1% and very good in 48.9%. The results of this open label study suggest that the combination of L-DOPA standard in the morning and L-DOPA slow release formulation at the following time points can be an efficient therapy in parkinsonian patients who suffer form L-DOPA related end-of-dose motor akinesia.

Adult↗

[Life expectancy and disability in Parkinson disease].

Idiopathic Parkinson's disease is a chronic progressive neurodegenerative disease with no possibility of curative treatment up until now. The natural course leads to severe handicap or death within 10-15 years, but due to the development of dopaminergic drug therapy life expectancy of parkinsonian patients has normalized and productivity remains good for a longer period during the course of disease.

Aged↗

Dystonia in ataxia telangiectasia: report of a case with putaminal lesions and decreased striatal [123I]iodobenzamide binding.

A 6-year-old girl with ataxia telangiectasia and severe progressive dystonic posturing is presented. Magnetic resonance imaging showed cerebellar atrophy and a right-sided putaminal lesion. A single-photon emission computed tomography study of cerebral dopamine-(D2)-receptor binding with [123I]iodobenzamide showed a decreased tracer uptake in the striatum bilaterally. Dystonia deteriorated with levodopa treatment, whereas trihexyphenidyl led to significant improvement. Although dystonic symptoms have been repeatedly described in ataxia telangiectasia, this is the first report demonstrating structural and functional basal ganglia abnormalities in this disorder.

Ataxia Telangiectasia↗

Perseverative motor behaviour in Parkinson's disease.

Difficulties in shifting of cognitive sets and perseverative behaviour have been shown to be part of the neuropsychology of Parkinson's disease, possibly due to frontal dysfunction. We have tested perseverative motor behaviour by assessing ability to generate random movement sequences in 15 patients with Parkinson's disease using the Breidt Perseveration Test Device (PTD). In this experiment subjects are instructed to press one of nine buttons arranged randomly on a metal board without use of systematic or repetitive strategies. The speed of this task that comprises 150 consecutive presses is determined by an acoustic go-signal appearing at 1 Hz frequency. Results were compared with 14 age-matched controls. Patients performance was impaired with intrusion of unwanted systematic strategies suggesting a decreased ability of Parkinson patients to generate random movement sequences.

Adult↗

Absence of disease related prion protein in neurodegenerative disorders presenting with Parkinson's syndrome.

Movement disorders presenting with parkinsonism may share histopathological features with Creutzfeldt-Jakob disease, a spongiform encephalopathy caused by the accumulation of pathological prion protein in brain. To investigate a possible aetiological link between these conditions and Creutzfeldt-Jakob disease, histoblot immunostaining for pathological prion protein was carried out in 90 cases including idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, Steele-Richardson-Olszewski syndrome, corticobasal degeneration, and Pick's disease. Pathological prion protein was identified in four controls with Creutzfeldt-Jakob disease but not in any of the other diseases examined. The findings suggest that an aetiological role for prions in these movement disorders is unlikely. Histoblotting provides a useful method for screening large areas of tissue for the presence of pathological prion protein and may be helpful in the differential diagnosis of difficult cases.

Brain↗

[Presynaptic nigrostriatal function in Parkinson disease and Parkinson-plus syndromes. Comparative studies using positron emission tomography with L-6-(18F)fluorodopa].

L-6-[18F]fluorodopa PET is suitable to assess the presynaptic nigrostriatal function within the living human brain. The purpose of this study was to compare the striatal rate constant Ki for L-6-[18F]fluorodopa in patients with Parkinson's disease (PD), Parkinsonism plus syndromes (PPLUS) and controls. 27 patients (m: 13, f: 14) between 36 and 75 years and 20 controls (m: 10, f: 10) between 20 and 85 years were examined. The clinical severity of the akinesia and rigidity were rated on the modified Columbia scale. In patients with PD the mean value of Ki was determined to be 0.339 +/- 0.098 [ml/striatum/min], in PPLUS 0.161 +/- 0.083, and in controls 0.708 +/- 0.121. The values of Ki were significantly different among the three groups (P = 0.001, ANOVA). The side-to-side difference D % of Ki was calculated to be 9.1% +/- 6.8% in PD, 14.2% +/- 10.9% in PPLUS, and 5.1% +/- 5.5% in controls (P = 0.079 PD vs. controls, 0.172 PD vs. PPLUS, and P = 0.003 PPLUS vs. controls). Ki values and rating on the Columbia scale did not show a strong correlation in both PD and PPLUS. In conclusion, the presynaptic nigrostriatal function seems to be more affected in PPLUS compared with PD. These findings may support the hypothesis of a "levelling-off" of the dopaminergic function in PD.

Adult↗

Dopamine D2 receptor imaging with iodine-123-iodobenzamide SPECT in idiopathic rotational torticollis.

UNLABELLED: The cause of idiopathic rotational torticollis (IRT) is not completely understood to date. However, basal ganglia are believed to be involved in the pathophysiology of IRT. To elucidate this disorder further, the value of iodobenzamide (IBZM) SPECT was studied for the evaluation of striatal dopamine D2 receptors in these patients. METHODS: Striatal dopamine D2 receptor density was assessed in 10 patients with IRT using 123I-IBZM SPECT. The images were interpreted by a nuclear medicine physician initially to determine IBZM binding within the striatum and the cerebellum and, secondly, interstriatal IBZM binding. The results were correlated with the clinical parameters of the patients and compared with the results obtained from normal controls. RESULTS: No difference was found in average, specific striatal IBZM binding (basal ganglia/cerebellum ratio) between patients and controls. However, interstriatal analysis of IBZM binding revealed a significantly higher binding in the striatum contralateral to the direction of the torticollis (p = 0.026, by chi-square test). CONCLUSION: It was concluded that the striatal dopamine D2 receptor status is altered in patients with IRT.

Adult↗

Correlation of clinical response in apomorphine test with D2-receptor status as demonstrated by 123I IBZM-SPECT.

The knowledge of functional capacities of postsynaptic dopaminergic receptors in parkinsonian syndromes is important for differential diagnosis and for planning therapeutic approaches. Subcutaneous apomorphine challenges serve as a pharmacological tool in testing dopaminergic responsiveness, but discrepancies between results of the apomorphine test and long-term levodopa treatment remain. 123I IBZM (I-123 labeled iodobenzamide) as a dopaminergic receptor ligand allows depiction of D2-receptors by means of SPECT methods. The correlation between dopaminergic responsiveness and D2-receptor status as demonstrated by 123I IBZM-SPECT imaging was assessed by applying an apomorphine test to 41 patients with parkinsonian syndromes. All subsequently underwent an 123I IBZM-SPECT. Apomorphine responders showed a significantly higher binding of 123I IBZM than nonresponders, and patients with idiopathic Parkinson's disease (IPD) had higher D2-receptor density as visualized by SPECT than patients with other parkinsonian syndromes. The marked overlap between the groups allowed a reliable prediction only in patients with an abnormally low basal ganglia/frontal cortex ratio of 123I IBZM binding.

Adult↗

3H-spiperone binding to lymphocytes fails in the differential diagnosis of de novo Parkinson syndromes.

In order to investigate the diagnostic value of 3H-spiperone binding capacity to lymphocytes in the differential diagnosis of de novo Parkinson's disease (idiopathic Parkinson syndrome, PD), we performed a double blind prospective study of spiperone binding capacity of 123 patients and 23 healthy control persons, belonging to different diagnostic groups (PD, Parkinsonian syndrome due to vascular lesions, multiple system atrophy [MSA], essential tremor). Diagnoses were based on medical history, clinical examination, CT or MRI scan, acute response to dopamimetic drugs, one year follow up, and long term response to L-DOPA treatment. Spiperone binding was assayed using ten different concentrations (0.03-3 nmol) in absence or presence of 1 mumol (+)-butaclamol to determine nonspecific binding. There was no significant difference in spiperone binding between patients with PD not treated with L-DOPA, and patients with other basal ganglia disorders including parkinsonian syndrome due to vascular lesions, multiple system atrophy, or progressive supranuclear palsy, and age matched controls. Binding was significantly higher in parkinsonian patients with PD treated with L-DOPA and patients with essential tremor. It is concluded that at present 3H-spiperone binding gives no further information in the differential diagnosis of de novo Parkinson's disease.

Adult↗

[The differential diagnosis of Parkinson diseases--123I-IBZM-SPECT vs. the apomorphine test].

The aim of our study was to compare the striatal dopamine D2-receptor density as measured by 123I-IBZM-SPECT with the results of the apomorphine-test. 30 patients were studied; 21 with idiopathic Parkinson's disease (IPD), 9 with Parkinson plus syndromes (PPS). Patients with IPD showed a significantly higher striatal IBZM binding as compared to patients with PPS (p = 0.006). A good correlation between IBZM binding and outcome of the apomorphine-test was found (p = 0.006). Low striatal IBZM binding indicates reduced dopamine D2-receptor density. This compromises successful dopaminergic medical therapy and is indicative of non-IPD disease. 123I-IBZM-SPECT could be diagnostic aid in the work-up of patients with extrapyramidal movement disorders. The response to dopaminergic drug treatment might be precluded by IBZM-SPECT in patients with Parkinsonian syndromes.

Adult↗

Current strategies in the drug treatment of advanced Parkinson's disease--new modes of dopamine substitution.

Oral levodopa treatment remains the most efficacious treatment of Parkinson's disease, but the majority of patients treated with a levodopa monotherapy for more than 5 years will develop fluctuations and/or dyskinesias. Important pathophysiological mechanisms are peripheral factors resulting in fluctuating levodopa blood concentrations and central pharmacodynamic changes, possibly due to chronic pulsatile stimulation of dopamine receptors. Continuous dopaminergic stimulation is able to smooth out a fluctuating response to oral levodopa and reduce 'off period' dystonia and the intensity of 'peak dose' dyskinesias. New drug delivery techniques include 'slow release' levodopa preparations and subcutaneous infusions of apomorphine. Future methods of transcutaneous or intramuscular application of dopamine agonists are under development. These methods may help to improve the results of long-term levodopa treatment of parkinsonian patients.

Antiparkinson Agents↗

Use of botulinum toxin in the treatment of cervical dystonia.

Idiopathic cervical dystonia, like other adult-onset focal dystonias, has been notoriously difficult to treat. Multiple approaches, including systemic drug treatment with anticholinergics, antidopaminergics, anticonvulsants, muscle relaxants and many other drugs as well as physiotherapy and psychotherapy, usually lead to only temporary amelioration in a minority of patients. Surgical selective EMG-controlled denervation of dystonic neck muscles produces better and, in the hands of some, lasting improvement. However, the procedure is invasive and as such less well accepted by patients. Local injections of botulinum toxin are strikingly successful in improving postural deviation and pain in about 80% of patients. They can be made on an outpatient basis and appear to be safe even over many repeat sessions. Dysphagia is potentially the most serious side-effect but can be decreased in incidence and severity by injecting lower doses, particularly into the sternomastoid. Major drawbacks at present are a lack of prospective data to establish optimal dosage and volume of injection guidelines to preserve good efficacy at a reduced risk of side-effects, and the need to continue indefinitely with repeat injections approximately every 3 months.

Botulinum Toxins↗

Clinical and pathophysiologic aspects of late levodopa failure.

More than 50% of all patients with Parkinson's disease who initially receive treatment with conventional levodopa will develop late complications, although the underlying mechanisms are not completely understood. Some aspects of levodopa peripheral pharmacokinetic handling contribute to response fluctuations, such as its short half-life and the variations of gastrointestinal absorption and blood-brain barrier transport caused by competition with neutral amino acids. In themselves, however, these are insufficient to explain the late occurrence of "on-off" oscillations. Disease-related central changes in presynaptic handling of levodopa are likely to play a role, as are postsynaptic pharmacodynamic receptor changes, possibly induced by chronic, nonphysiologic, pulsatile stimulation. Pharmacodynamic alterations of dopaminergic receptors have also been implicated in the pathogenesis of levodopa-induced dyskinesias. Recent experimental findings suggest a possible role of downstream functional changes in pallidosubthalamo-thalamic projections.

Dyskinesia, Drug-Induced↗

How to run a "brain bank"? Clinical and institutional requirements for "brain banking".

"Brain Banking" or prospective sampling of tissues relevant to the study of neurological disease is a complex task which needs organization at various levels of operation such as the establishment of a donor system, recruitment of clinical assessment centres, establishment of standardized assessment protocols, the inauguration of logistic structures for brain removal and transport to the bank, proper storage of patient data and tissues, histological verification of the disease and availability of tissue and clinical data to researchers. This effort certainly promises to bear fruit since there is a striking lack of precise prospective studies into etiology and pathogenesis in most neurological diseases especially in the field of the neurodegenerative diseases.

Brain↗