[A biomechanical analysis of cyclical hand motor function: a pilot study in different Parkinsonian syndromes]. / Biomechanische Analyse zyklischer Handfunktionen : Eine Pilotstudie bei unterschiedlichen Parkinson-Syndromen.

INTRODUCTION: Clinical assessment of hand bradykinesia in Parkinson's disease (PD) focuses mainly on the frequency, amplitude and rhythm of movements, thereby subjectively evaluating the correct performance of hand movements. The aim of the study was to quantify hand bradykinesia with kinematic data in different Parkinsonian syndromes. PATIENTS AND METHODS: This retrospective study compared patients with idiopathic PD (IPD, n = 18), atypical Parkinson's syndrome (APS, n = 17), secondary Parkinson's syndrome (SPS, n = 18) and healthy controls (C, n = 18). All patients were receiving the best medical treatment. Hand movements were recorded using an ultrasound-system (Zebris®, Isny, Germany). Subjects were asked to perform pronation/supination of the forearm (diadochokinesis), flexion/extension of the hand (hand tapping) and tapping of the index finger. Mean amplitude, mean frequency and mean variability of movements were determined. RESULTS: APS patients had significant complex hand movement disability with reduced amplitude and frequency in combination with increased motion variability in all movement tasks. The key disturbance in the IPD group concerned the rhythm in hand tapping and index finger tapping in combination with moderately reduced velocity and range of motion in all conditions. The cyclical hand movement characteristics in SPS patients showed movement slowness with normal amplitude and variability in all motor conditions. CONCLUSION: Our results suggest that computerized quantitative analysis of cyclical hand movements can characterize and identify different representations of hand bradykinesia in different Parkinsonian disorders and hence may help clinicians to accurately assess therapeutic targets and outcome of interventions.

[Static posturography in selected Parkinson syndromes: quantitative analysis of postural control]. / Statische Posturographie bei ausgewählten Parkinson-Syndromen : Quantitative Beurteilung der posturalen Kontrolle.

OBJECTIVES: Idiopathic Parkinson's disease (IPD) is associated with postural disturbances and falls. The assessment of postural instability by the pull test may lead to inconclusive results. Static posturography measurements may give more reliable information regarding the differential diagnosis of Parkinson syndromes. PATIENTS AND METHODS: We compared results of the pull test and static posturography (sway area in eyes-open/eyes-closed conditions) in healthy controls (C) and patients with akinetic-rigid IPD (n=18), atypical Parkinson syndromes (APS; n=18) and secondary Parkinson syndromes (SPS; n=17). RESULTS: Static posturography and the pull test results did not differ significantly between controls and patients with akinetic-rigid IPD. APS patients had significantly greater postural sway areas when tested with eyes open compared to controls (APS: 16.89 vs C: 6.89 mm, p≤0.001) and IPD patients (APS: 16.89 vs IPD: 9.55 mm, p=0.005). The correlation in the APS group between the pull test and sway area in the eyes-open condition was significant (r=0.526, p=0.025). With eyes closed, postural instability in APS patients was not significantly increased (+2%, p=.847). SPS patients were more unstable under the eyes-closed condition compared to controls (sway area SPS: 26.29 vs C: 8.79 mm, p≤0.001), IPD patients (sway area SPS: 26.29 vs IPD: 11.06 mm, p≤0.001) and APS patients (sway area SPS: 26.29 vs APS: 17.28 mm, p=0.027), without a significant correlation to the pull test. The sway area in the SPS patients increased significantly by 67% (p=0.001) under the eyes-closed condition. CONCLUSION: Static posturography may be a helpful tool for the differentiation of Parkinson syndromes.

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register.

BACKGROUND: We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non-Austrian centres as documented in the Internet-based registers Safe Implementation of Thrombolysis for Stroke - MOnitoring STudy (SITS-MOST) and - International Stroke Thrombolysis Register (SITS-ISTR). METHODS: We analysed patient data entered in the registers SITS-MOST and SITS-ISTR in the period December 2002 to 15 November 2007. RESULTS: Compared to the non-Austrian cohort (n=15153), the Austrian cohort (n=896) was slightly older [median, interquartile range (IQR): 70, 60-77 years vs. 69, 60-76 years, P=0.05] and included more women (44.6% vs. 41.0%, P=0.03). Austrian patients had a significantly shorter stroke onset-to-treatment time (OTT; median, IQR: 135, 105-160 min vs. 145, 115-170 min, P<0.0005). Symptomatic intracerebral haemorrhages were observed in 1.6% of Austrian and 1.7% of non-Austrian patients (P=0.82). At 3 months, 50.8% of Austrian and 53.0% of non-Austrian patients were independent (P=0.23), but death was less frequent in Austrian patients (12.1% vs. 14.9%, P=0.03). Multivariate analyses adjusted for demographic and baseline characteristics confirmed lower mortality at 3 months in the Austrian cohort (odds ratio 0.81, 95% confidence intervals 0.71-0.92, P=0.001). Longer OTT was associated with increased mortality at 3 months, with a hazard ratio of 1.02 (95% CI 1.01-1.03; P=0.005) for each 10-min increase in OTT. CONCLUSIONS: The implementation of intravenous alteplase for acute stroke has been safe and efficacious in Austrian centres. OTT and mortality were significantly lower in Austrian patients compared to non-Austrian SITS centres.

Worse blood pressure control in patients with cerebrovascular or peripheral arterial disease compared with coronary artery disease.

OBJECTIVES: Poor blood pressure (BP) control is common amongst patients with symptomatic atherothrombotic disease. It is unclear whether BP control and management differ across atherothrombotic disease subtypes. METHODS: We analysed the baseline data of 44,984 patients with documented coronary artery disease (CAD) only (n = 30,414), cerebrovascular disease (CVD) only (n = 11,359) and peripheral arterial disease (PAD) only (n = 3211) from the international REduction of Atherothrombosis for Continued Health Registry and investigated the impact of atherothrombotic disease subtype on BP control and use of antihypertensive drugs. RESULTS: The proportion of patients with BP controlled (<140/90 mmHg) was higher in CAD (58.1%) than in CVD (44.8%) or PAD (38.9%) patients (P < 0.001). Amongst patients with treated hypertension, CAD patients were more likely to have BP controlled than were CVD patients [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.59-1.75] or PAD (OR = 2.30; 95% CI = 2.10-2.52). These differences were smaller in women than in men and decreased with age. Amongst treated patients, CAD patients were more likely to receive > or =3-drug combination therapies than were CVD (OR = 1.73; 95% CI = 1.64-1.83) or PAD (OR = 1.64; 95% CI = 1.49-1.80) patients. Adjustment for age, gender, waist obesity, diabetes, education level and world region did not alter the results. CONCLUSIONS: Coronary artery disease patients are more likely than CVD or PAD patients to have BP controlled and to receive antihypertensive drugs, particularly combination therapies. Promotion of more effective BP control through combination antihypertensive therapies could improve secondary prevention and therefore prevent complications in CVD and PAD patients.

High cardiovascular event rates in patients with asymptomatic carotid stenosis: the REACH Registry.

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.

Postprocedural high-density lipoprotein cholesterol predicts carotid stent patency at 1 year.

The durability of carotid artery stenting (CAS) is affected by the occurrence of myointimal proliferation and in-stent restenosis (ISR). We aimed to identify clinical, angiographic, and laboratory predictors of ISR, paying special attention to postprocedural metabolic factors. A total of 102 consecutive patients with successful CAS for > or =70% atherosclerotic internal carotid artery stenosis were followed up with neurological assessment and duplex sonography 1 day, 1 month, and 1 year after CAS. Lipid profile and hemoglobin A(1c) were tested at the 1-month follow-up visit. Ten (10%) patients had ISR > or =50% after 1 year. Compared with patients without ISR (n = 92), patients with ISR were more often current smokers (33% vs. 70%, P = 0.034) and had significantly lower 1-month high-density lipoprotein (HDL) cholesterol: median (range) 47 (24-95) mg/dl vs. 39.5 (25-50) mg/dl, P = 0.031. Multivariate logistic regression analyses identified 1-month HDL cholesterol >45 mg/dl as the only independent predictor of carotid stent patency at 1 year (P = 0.033, OR = 0.09, 95% CI 0.01-0.83). Postprocedural HDL cholesterol levels predict carotid stent patency at 1 year. With the possibility of elevation of HDL cholesterol by lifestyle changes and medication, this finding may have implications for the future management of patients undergoing CAS.

Timing of stenting of symptomatic carotid stenosis is predictive of 30-day outcome.

For patients with symptomatic carotid stenosis, benefit from carotid artery stenting (CAS) highly depends on the 30-day stroke and death rates. Identification of predictors of unfavourable outcome would help guide the patient selection. We analysed the influence of clinical and angiographic factors on the 30-day outcomes of 77 consecutive patients who underwent CAS for > or = 60% symptomatic carotid stenosis within 180 days of transient ischaemic attack or moderate stroke (modified Rankin Scale score < or = 3). The 30-day composite end-point for stroke (7.8%) and death of any cause (1.3%) was 9.1%. Patients with complicated CAS were older than patients with uncomplicated CAS (mean age 75.1 +/- 8.2 vs. 65.9 +/- 9.5 years, P = 0.015) and underwent stenting significantly earlier after the qualifying event: median delay 1.5 weeks (range: 0.2-3.0) vs. 3.2 weeks (range: 0.5-26), P = 0.004. In multivariate logistic regression analyses, age [odds ratio (OR) = 1.148; 95% confidence interval (CI): 1.011-1.304 and P = 0.033] and delay of treatment < 2 weeks (OR = 22.399; 95% CI: 2.245-223.445 and P = 0.008) remained the only variables significantly associated with 30-day outcome. CAS carries a considerable risk in old patients and when performed early (< 2 weeks) after the qualifying event. Future reports should address the timing of CAS.

The natural course of Sneddon syndrome: clinical and magnetic resonance imaging findings in a prospective six year observation study.

Sneddon syndrome (SS) is increasingly recognised as a cause of ischaemic stroke in young adults. As the natural course of SS is not well defined, the authors performed a prospective six year clinical and neuroradiological follow up study. Thirteen patients with definite diagnosis of SS (livedo racemosa, characteristic skin biopsy, and history of stroke) entered a follow up programme that consisted of clinical examinations, two magnetic resonance imaging (MRI) investigations, and a comprehensive laboratory follow up protocol. The most frequent clinical findings during follow up had been headache (62%) and vertigo (54%). Seven patients (54%) suffered from transient ischaemic attacks, however, completed stroke has not been obtained during follow up. Progression of white matter lesions detected in MRI were present in 10 of 13 patients. Laboratory follow up protocol revealed transient antiphospholipid antibodies in two subjects. This prospective six year follow up study suggests a low incidence of territorial stroke but outlines progressive leucencephalopathy in patients with SS.

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.

The impact of peak saturation of the arterial input function on quantitative evaluation of dynamic susceptibility contrast-enhanced MR studies.

PURPOSE: The purpose of this work was to investigate systematic errors in dynamic contrast-enhanced MR perfusion studies due to peak saturation of the arterial input function (AIF) and to introduce a simple correction algorithm. METHOD: Computer simulations were performed to evaluate the influence of AIF peak saturation and to demonstrate the effectiveness of the presented correction algorithm. To compare the computer simulations with real MR data, MR perfusion measurements were performed on volunteers. RESULTS: The computer simulations show that AIF peak saturation leads to a systematic overestimation of cerebral blood volume (CBV) and cerebral blood flow (CBF) values, which was confirmed by comparing the obtained MR data with PET results. With use of an improved calculation algorithm correcting for AIF peak saturation, a significant improvement of the obtained CBV and CBF values could be demonstrated. CONCLUSION: Our results suggest that AIF peak saturation leads to a significant systematic error in the determination of CBV and CBF values and has necessarily to be taken into account for dynamic contrast-enhanced MR perfusion studies.

Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs.

OBJECTIVES: We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). BACKGROUND: It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation. METHODS: After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation. RESULTS: All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology. CONCLUSIONS: During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial (MAHST).

BACKGROUND AND PURPOSE: Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS: MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial. RESULTS: Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event. CONCLUSIONS: Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.

MR volumetry for monitoring intramuscular bromocriptine treatment in macroprolactinomas.

OBJECTIVE: To assess volumetric changes of pituitary prolactinomas, we applied a threshold-based segmentation algorithm in two patients during intramuscular bromocriptine treatment. MATERIALS AND METHODS: Tumor volumes were calculated from contiguous slices of a 3D GE sequence and from conventional SE images. RESULTS: After a single 50 mg i.m. bromocriptine administration, the prolactinoma volumes decreased by 25 and 35% within 7 and 11 days, respectively. Volume calculations from 3D GE images were more accurate than calculations from 3 mm 2D SE images, especially for smaller tumors. A decrease of prolactinoma size was paralleled by a decrease of serum prolactin levels and correlated with an improvement of visual field and endocrine function in both patients. The end of the bromocriptine effect was indicated by a reincreasing tumor volume, which was observed after 30 days in the first patients and after 43 days in the second patient. CONCLUSION: Our results suggest that MR volumetry represents a useful tool to monitor changes of prolactinoma volume during bromocriptine treatment and may improve the clinical management of these patients.

MR imaging and proton spectroscopy of the brain in posttraumatic cortical blindness.

Magnetic resonance (MR) imaging and localized proton MR spectroscopy of the occipital lobes were performed in a patient with cortical blindness following brain trauma. Computed tomography (CT) scans and MR images of the visual cortex were normal in the acute stage. Six weeks after the trauma, MR images showed cortical lesions in both occipital lobes, while the spectra showed elevated lactate and decreased N-acetyl aspartate levels relative to those of healthy volunteers. One year later, visual acuity had improved and follow-up studies revealed an increase in the ratios of N-acetyl aspartate to choline and creatine. These results demonstrate that parenchymal lesions may develop in brain regions that appear normal at CT and MR imaging during the acute stage after trauma. Metabolic changes can be observed in these areas by means of localized proton MR spectroscopy.

Sneddon's syndrome: diagnosis by skin biopsy and MRI in 17 patients.

BACKGROUND AND PURPOSE: Sneddon's syndrome, characterized by generalized livedo racemosa and cerebrovascular lesions, is an underdiagnosed disease. We evaluated clinical, laboratory, histological, and neuroradiological findings in a series of 17 patients to improve diagnostic criteria for Sneddon's syndrome. METHODS: Patients with generalized livedo racemosa and cerebrovascular events were included in the study. All underwent neurological and dermatological examination, skin biopsy, computed tomographic scan, magnetic resonance imaging as well as magnetic resonance angiography, sonography of the extracranial arteries, and a comprehensive laboratory protocol. RESULTS: Completed stroke was present in eight patients, and 15 reported transient neurological deficits. Magnetic resonance imaging yielded cerebral abnormalities in 16 of 17, whereas computed tomographic scans were abnormal in only 12 of 16 patients. Magnetic resonance imaging revealed more lesions in individual patients than did computed tomography. Magnetic resonance angiography demonstrated patent intracranial vessels in 16 of 17 patients. Skin biopsy showed distinct histopathological findings in all patients. The involved vessels were small to medium-sized arteries at the border between dermis and subcutis. Early inflammatory reactions were followed by subendothelial proliferation and a late fibrotic stage. Laboratory examinations showed impaired creatinine clearance in eight patients, whereas all other laboratory tests, including antiphospholipid antibodies, were normal. CONCLUSIONS: In this series, magnetic resonance imaging and skin biopsy were useful for confirmation of the diagnosis of Sneddon's syndrome. Magnetic resonance findings were not specific, but the high sensitivity for detection of asymptomatic brain lesions helped to confirm the diagnosis in patients with transient symptoms. Histological features of skin biopsies were characteristic if appropriate techniques were employed.

Localized proton and phosphorus magnetic resonance spectroscopy following electroconvulsive therapy.

Animal studies show that cerebral lactate increases after electrically induced seizures. We investigated three adult psychiatric patients by means of localized proton and phosphorous magnetic resonance spectroscopy in order to evaluate if such effects can be observed after electroconvulsive therapy (ECT). None of the patients had changes in cerebral energy metabolism following ECT. Within the limitations of in-vivo spectroscopy in a clinical setting, our results suggest that if lactate production increases after ECT, this effect is either very short or increased perfusion causes an efficient efflux of cerebral lactate.

Combined magnetic resonance imaging and proton magnetic resonance spectroscopy of patients with acute stroke.

BACKGROUND AND PURPOSE: The prospect for a therapeutic window for treatment of ischemic stroke encourages the noninvasive investigation of metabolic changes in acute ischemia. Recently, localized proton spectroscopy became available at 1.5-T magnetic resonance systems. In this study we evaluated the usefulness of combined magnetic resonance imaging and spectroscopy on the diagnosis of acute and chronic infarctions. METHODS: Combined magnetic resonance imaging and spectroscopy investigations were carried out with a 1.5-T system in 16 volunteers, eight patients with chronic infarction (greater than 8 months), and 10 patients with acute ischemic stroke (less than 8 hours). We used a stimulated echo sequence to acquire localized spectra from image-guided volumes of interest (16-27 ml). RESULTS: There were no significant interindividual differences of choline, creatine, phosphocreatine, and N-acetyl aspartate resonances in the spectra from volunteers. In chronic infarctions, N-acetyl aspartate was decreased in relation to choline. Acute ischemic infarctions were characterized by decreased N-acetyl aspartate resonances and elevation of lactate. CONCLUSIONS: The study demonstrates the feasibility of proton spectroscopy in stroke patients. Metabolic alterations in ischemic tissue can be monitored and can distinguish acute from chronic lesions.