Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study.

BACKGROUND AND PURPOSE: Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies. METHODS: A single-centre double-blind randomized placebo-controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty-two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase. RESULTS: Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow-up data and at week 24 (P < 0.01). CONCLUSIONS: The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment.

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

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.

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.

Iodine-123-iodo-lisuride SPECT in Parkinson's disease.

UNLABELLED: Recently, [123I]iodo-lisuride was synthesized for possible applications in SPECT studies. The purpose of this investigation was to compare the striatal binding and kinetics of this radioligand in patients with Parkinson's disease and normal controls. METHODS: Six patients with Parkinson's disease and three normal controls were examined. After intravenous injection of 111 MBq [123I]iodo-lisuride, sequential SPECT examinations at 20, 40, 80 and 120 min were performed. For each SPECT series the basal ganglia-to-cerebellum ratio of tracer accumulation was calculated. In one patient a repeat SPECT examination was undertaken under identical conditions to test the reproducibility of the procedure. In two other patients a second SPECT examination was performed after injection of cold lisuride as a receptor saturation study. In addition, the time course of the radioactivity was measured in the plasma and red blood cells in each individual. RESULTS: In both patients and controls, the highest tracer accumulation was found within the striatum. The basal ganglia-to-cerebellum ratio was 1.182 and 1.303 at 20 min, 1.353 and 1.450 at 40 min, 1.490 and 1.533 at 80 min, 1.550 and 1.583 at 120 min for patients and controls, respectively, which was not statistically different. In the saturation study, 50 micrograms and 100 micrograms cold lisuride led to a 28% and 33% reduction, respectively, of the basal ganglia-to-cerebellum ratio at 120 min. The ligand showed a rapid decline in plasma and red blood cells. The percent injected dose per liter was calculated to be 1.6 and 0.9, respectively, for plasma and red blood cells at 20 min. CONCLUSION: Iodine-123-iodo-lisuride SPECT seems useful for imaging intact striatal dopamine D2 receptors in patients with Parkinson's disease and may provide clinically relevant information for quantitative assessment of the availability and integrity of dopamine D2 receptors.

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.

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.

Treatment of spasmodic torticollis with local injections of botulinum toxin. One-year follow-up in 37 patients.

Thirty-seven patients with spasmodic torticollis (cervical dystonia) who received repeated local injections of botulinum toxin have been followed up for a mean period of 12.3 (10-29) months, during which time 138 treatment sessions were performed. Mean doses per muscle averaged 320 mouse units (mu; range 160-1000 mu botulinum toxin A prepared by CAMR, Porton Down, UK). Eighty-six per cent of patients experienced significant improvement of posture and 84% of those with pain had relief following the first injection. Muscular patterns of recurrent torticollis were relatively constant and in most patients efficacy was maintained with subsequent injections, while 15% of all follow-up sessions failed. Only 2 of 37 patients were consistent nonresponders; 22% and 10% of all sessions were complicated by transient dysphagia and weakness of neck muscles, respectively. It is concluded that local botulinum toxin injections can be a safe and efficaceous long-term treatment of spasmodic torticollis and that optimal doses should be between 200 and 400 mu/muscle.

Effects of treatment with trihexyphenidyl on cognitive function in early Parkinson's disease.

13 patients with PD of recent onset underwent a series of neuropsychological tests for frontal lobe associated functions (Sternberg paradigm, WCST, CVLT) before and during treatment with Artane. Test results at baseline were not significantly different from those of an age-matched control group (n = 13). Retesting after a mean of 2 weeks' treatment with trihexyphenidyl revealed only slight impairment in CVLT while performance on the other tests remained unchanged.

[The differential diagnosis of Parkinson diseases--123I-IBZM-SPECT vs. the apomorphine test]. / Differentialdiagnose der Parkinson-Erkrankungen--123I-IBZM-SPECT vs. Apomorphin-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.

[Magnetic resonance tomography in patients with Parkinson's disease and Parkinson-plus syndromes]. / Magnetresonanztomographie bei Patienten mit Morbus Parkinson und Parkinson-Plus-Syndromen.

PURPOSE: To define characteristic MR-findings in patients with clinically typical extrapyramidal movement disorders. METHODS: 15 patients with Parkinson's disease (PD), 9 with multisystem atrophy (MSA), and 6 with progressive supranuclear palsy (PSP) underwent MRI using a 1.5 T. Magnetom unit. Two investigators analysed the images with special regard to global and/or focal atrophy and to changes in signal intensity of the CNS in the consensus mode. Normal images of 10 subjects served as controls to patient's images. RESULTS: In all patients with PSP and MSA characteristic pathological findings on MRI were observed including regional changes within the extrapyramidal nuclei. In contrast all patients with PD had an unremarkable MRI study of the CNS. CONCLUSION: MRI enables us to define characteristic morphological changes of the brain in patients with extrapyramidal movement disorders. Early recognition of these findings avoids misdiagnoses in patients who are difficult to diagnose.

[The determination of cerebral dopamine (D2) receptor density by using 123I-IBZM-SPECT in Parkinson disease patients]. / Bestimmung der zerebralen Dopamin-(D2)-Rezeptoren-Dichte mit Hilfe der 123Jod-IBZM-SPECT bei Patienten mit Morbus Parkinson.

An alteration of the dopaminergic nigrostriatal system is believed to be the main pathogenetic factor of Parkinson's disease (PD). We report on our initial results on the determination of the post-synaptic dopamine-D2-receptor binding of 123I-IBZM in patients with PD. Drug-native patients showed a significantly higher IBZM binding in the basal ganglia as compared to patients on specific dopaminergic medication. Age, duration of the disease and the severity of the disease do not seem to influence the IBZM-receptor binding. We conclude that 123I-IBZM-SPECT is an extremely useful tool for the evaluation of the functional state of cerebral dopamine-D2-receptors.

[Brain SPECT with 123I-lisuride in patients with Parkinson's disease and controls]. / Hirn-SPECT mit 123I-Lisurid bei Morbus-Parkinson-Patienten und Kontrollen.

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.

Lack of selective vulnerability to anticholinergic induced cognitive impairment in early Parkinson's disease.

Thirteen patients with idiopathic Parkinson's disease of recent onset (mean age 63·2 years) and a group of 10 young healthy volunteers (mean age 26·1 years) underwent a series of neuropsychological tests for assessment of memory, learning ability and mental processing speed before and during treatment with trihexyphenidyl. Retesting after anticholinergic exposure (mean of 2 weeks for patients and 1 week for controls) revealed in young healthy controls the same pattern and magnitude of decline in memory function as in Parkinson patients. Non-demented subjects with Parkinson's disease of recent onset thus do riot seem to be selectively vulnerable to cognitive side-effects of anticholinergic treatment.

[Life expectancy and disability in Parkinson disease]. / Lebenserwartung und Invalidität bei Morbus Parkinson.

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.

High-speed memory scanning in Parkinson's disease: adverse effects of levodopa.

High-speed memory scanning as assessed by the Sternberg paradigm was studied in 12 nondemented patients with fluctuating Parkinson's disease and 13 age-matched healthy controls. Patients were first assessed before taking their morning dose of levodopa ("off") and again after that dose had produced full clinical effect ("on") after that dose had produced full clinical effect ("on"). Although motor components of the measured choice reaction time were slower in patients when off than in control subjects, memory scanning speed was not different. After levodopa (on), patients' motor time normalized, but cognitive processing speed became significantly slower when compared with previous performance in the off condition and with controls. Contrary to previous concepts of bradyphrenia in patients with Parkinson's disease, these results indicate that dopaminergic stimulation can reduce cognitive processing speed.

Reduction of Parkinsonian signs in patients with Parkinson's disease by dopaminergic versus anticholinergic single-dose challenges.

We investigated the effect of an anticholinergic (biperiden) and a dopamine agonist (apomorphine) on tremor, rigidity, and akinesia in patients with idiopathic Parkinson's disease. In a standardized, crossover study design 17 patients received single-dose challenges of 5 mg biperiden intravenously and a previously determined dose of apomorphine subcutaneously on 2 consecutive days. Resting (RT), postural (PT), and action tremor (AT) were assessed using spectral analysis of accelerometer data, and Unified Parkinson's Disease Rating Scale (UPDRS) scores for rigidity and akinesia were determined before and after administration of the study drug. Both single-dose challenges significantly reduced the amplitude of RT, PT, and AT, but only apomorphine significantly reduced UPDRS scores for rigidity and akinesia. In only one patient was tremor reduced by the dopamine agonist but not by the anticholinergic. We found that anticholinergic and dopaminergic agents are both effective in reducing tremor in IPD, and there was no evidence for a selective anticholinergic responsiveness of parkinsonian tremor. Akinesia and rigidity, on the other hand, were not improved by biperiden. We therefore conclude that dopaminergic substances are as effective as anticholinergics in patients with parkinsonian tremor and additionally improve other parkinsonian signs.