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Biomedical subjects

A Schrag

Publications and source records attributed to A Schrag.

53 records · Page 3Linked to original sources
PubMed1999

Sequential bilateral transplantation in Parkinson's disease: effects of the second graft.

Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.

Adult↗
PubMed1999

Unilateral pallidotomy for Parkinson's disease: results after more than 1 year.

OBJECTIVE: To examine follow up results of unilateral ventral medial pallidotomy in 22 patients with advanced Parkinson's disease more than 1 year after the operation in comparison with their results (previously reported) at 3 months. METHODS: Twenty patients who had undergone unilateral pallidotomy were assessed with the core assessment programme for intracerebral transplantation (CAPIT) protocol preoperatively, at 3 months postoperatively, and again after a median postoperative follow up of 14 months. Two further patients had only one evaluation 3 months postoperatively. RESULTS: The reduction of contralateral dyskinesias (median 67%) at 3 months was slightly attenuated after 1 year to 55% (both p<0.001 compared with baseline). A less pronounced effect on ipsilateral and axial dyskinesias decreased from 39% to 33% (p<0.005 and p<0.01), and from 50% to 12.5% (p<0.001 and p<0.01), respectively. However, there was no significant change between the 3 month and the follow up assessment. The modest improvement of the contralateral unified Parkinson's disease rating scale (UPDRS) motor score in the "off" state remained improved compared with preoperative levels, but less significantly (26%, p<0.001, and 18%, p<0.01). The activities of daily living (ADL) subscore of the UPDRS in the off state remained improved with median changes of 23% and 22% at follow up (both p<0. 005). There was no significant improvement of "on" state or ipsilateral off state motor scores. Median modified Hoehn and Yahr scores in off and on state were unchanged, as was the time spent off. Speech in off had significantly deteriorated by 1 year after the operation. CONCLUSIONS: The beneficial effects of unilateral pallidotomy persist for at least 12 months and, dyskinesias are most responsive to this procedure.

Adult↗
PubMed1998

Young-onset Parkinson's disease revisited--clinical features, natural history, and mortality.

The authors report on clinical features and mortality rates in a group of 149 patients with apparent idiopathic parkinsonism starting before the age of 40 years. Ten had juvenile parkinsonism (JP; onset before age 21 years) and 139 had young-onset Parkinson's disease (YOPD; onset at age 21 to 40 years). Included were 60 patients originally reported 10 years ago. Fifty percent of the JP group had a positive family history of parkinsonism in a first-degree relative, and clinical presentation was heterogeneous. Mortality risk was threefold that of the normal population. In the YOPD group, the mortality risk was double that of the normal population. Poor initial response to L-dopa was a risk factor for early death. In two previously reported patients, the diagnosis had been changed to multiple system atrophy and Machado-Joseph disease. After a median disease duration of 18 years, cognitive impairment was found in only 19% of YOPD patients (13% of those younger than 60 years and 43% of those 60 years or older). Age was the most important factor for development of dementia, but female sex and positive family history of parkinsonism also had more modest predictive value. After a disease duration of 10 years or less, only 5% of patients were experiencing falls and 30% freezing, but all patients had developed L-dopa-related fluctuations and dyskinesias. The authors conclude that the mortality rate in parkinsonism starting before the age of 40 is increased in comparison to the normal population and is similar to the general Parkinson's disease population. Intellectual function and postural reflexes are usually well preserved for many years despite a long history of parkinsonism and the early and frequent occurrence of treatment complications, provided the patients remain biologically and chronologically young.

Adolescent↗
PubMed1998

Huntington's disease and other choreas.

Chorea can have many causes, some hereditary and many sporadic in nature. The archetypal hereditary cause of chorea is Huntington's disease (HD). However, this condition often manifests as a mixed movement disorder, and some individuals with the Westphal variant may not display chorea at all. Moreover, since gene-specific testing has become available, we now know that in many cases of HD, particularly those with late onset, a positive family history may be lacking. In addition, dentatorubro-pallidoluysian atrophy (DRPLA), another dominantly inherited CAG repeat disease, can produce a similar clinical picture. In both conditions, the phenotype may vary according to repeat length, and anticipation and excess of paternal inheritance in younger-onset cases with longer repeat lengths are seen. Neuroacanthocytosis is probably genetically heterogenous, and many instances of "benign hereditary chorea" have been caused by other conditions. If it exists at all, this disorder is exceedingly rare. The principal causes of sporadic chorea include drugs, pregnancy, vascular disease, thyrotoxicosis, systemic lupus erythematosus (SLE) and the lupus anticoagulant syndrome, polycythaemia rubra vera, AIDS and both initial and recurrent Sydenham's chorea. The symptomatic treatment of chorea is unsatisfactory and, at least in HD, neuropsychiatric disturbance may be much more important for the family. Potential disease-modifying treatments such as anti-excitotoxins, antioxidants, free radical scavengers and neuronal grafting are now being explored in this condition.

Autoimmune Diseases↗
PubMed1998

A study of medial pallidotomy for Parkinson's disease: clinical outcome, MRI location and complications.

We have studied the effects of unilateral ventral medial pallidotomy in 26 patients with medically intractable Parkinson's disease with marked drug-induced dyskinesias. Preoperatively, all patients were assessed during one 5-day admission according to the Core Assessment Programme for Intracerebral Transplantation (CAPIT) protocol, including rating in the 'practically defined off' and 'best on' states before and during a single-dose levodopa challenge. Motor performance was assessed with subset categories of the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating scale. Pallidotomy was performed under stereotaxic CT guidance with intra-operative extracellular microelectrode recording made from the basal ganglia. All patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so far also been re-assessed after 1 year. Pre- and postoperative performance scores were compared in order to determine which categories of performance improved postoperatively. Significance was accepted at P < 0.005 in order to take into account the multiple number of comparisons performed. Patient medication was compared pre- and postoperatively and the morbidity associated with surgery was also recorded. The most significant improvement postoperatively was the diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however, ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score improved by 27% (P = 0.001) and a significant improvement was also observed in contralateral rigidity by 25% (P = 0.001). There were trends towards improvement in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013) scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral motor scores did not alter significantly. The 'off' gait/postural instability score and 'off' walking time showed marginally significant improvements by 7% (P = 0.007) and 29% (P = 0.014), respectively. On medication, no significant postoperative improvements in parkinsonism were detected. Anti-parkinsonian medication increased by 11% postoperatively. In the subgroup who were available for assessment 1 year postoperatively, responses were generally maintained. Two (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and one haemorrhagic infarct) directly related to surgery. Among the remaining 24 patients, four (15.4% of the total 26) had major complications (two persisting and two transient). Ten patients (38.5%) had minor complications. The majority of the complications (major and minor) occurred in the earlier operated patients and the complication rate subsequently declined with increasing operative experience. The remaining 10 patients (38.5%) had no significant side-effects. One of these 10 patients died from an incidental malignant glioma 6 months postoperatively. These findings confirm that levodopa-induced dyskinesias are dramatically reduced following ventral medial pallidotomy and constitute the principal indication for pallidotomy. Improvements in underlying parkinsonism were of smaller magnitude. Pallidotomy may also offer some patients an opportunity to increase antiparkinsonian medication. Patient selection for medial pallidotomy should, therefore, be based largely on anticipated improvements in levodopa-induced dyskinesias, but this must be balanced against the associated morbidity and mortality.

Aged↗
PubMed1998

Clinical usefulness of magnetic resonance imaging in multiple system atrophy.

OBJECTIVES: To determine the sensitivity, specificity, and positive predictive values of a selection of abnormal findings in the putamen and infratentorial structures on routine magnetic resonance imaging for distinguishing between multiple system atrophy, idiopathic Parkinson's disease, and age matched controls. PATIENTS AND METHODS: Two neuroradiologists blindly and independently rated axial T2 weighted and proton density MRI of 44 patients with multiple system atrophy, 47 patients with idiopathic Parkinson's disease, and 45 controls. High field (1.5 T) scans were available in 16 patients with multiple system atrophy, 15 patients with idiopathic Parkinson's disease, and 16 controls. All other patients had 0.5 T scans. RESULTS: On both 0.5 and 1.5 T scans the following items had high specificity but low sensitivity: putaminal atrophy, a hyperintense putaminal rim, and infratentorial signal change. Finding any infratentorial abnormality gave higher sensitivity but lower specificity. Putaminal isointensity or hypointensity relative to globus pallidus, absolute putaminal hypointensity, and altered size of the olives were not useful discriminators. The overall sensitivity was 73% on 0.5 T and 88% on 1.5 T scans. The specificities of these findings for multiple system atrophy in comparison to idiopathic Parkinson's disease and controls on 0.5 T were 95% and 100% respectively, and on 1.5 T were 93% and 91% respectively. Finding any of the described abnormalities on MRI gave a positive predictive value of 93% on the 0.5 T machine, and 85% on the 1.5 T scanner.

Adult↗
PubMed1996

[Magnetic resonance tomography in patients with Parkinson's disease and Parkinson-plus syndromes].

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.

Adult↗
PubMed1996

Directional bias of initial visual exploration. A symptom of neglect in Parkinson's disease.

In the present study, side preferences in spontaneous visual exploration were assessed systematically in 27 patients with idiopathic Parkinson's disease (IPD) and 17 age-matched controls. Assessment of initial visual exploration asymmetry (IVE) was based on the exploration of texture arrays requiring attentive oculomotor scanning. As shown in a previous study, most healthy subjects exhibit a marked asymmetry of IVE with a strong left-sided bias when assessed by this paradigm, while most neglect patients initiate exploration in the right half of the arrays. Standard assessments for symptoms of neglect (line bisection, line cancellation and double simultaneous stimulation) were performed as reference tests. In the IVE task 65% of normal controls and 69% of patients with predominantly right-sided IPD started exploration in the left half of the arrays. By contrast only 14% of patients with predominantly left-sided disease showed a leftward IVE. The majority shows an ambiguous (21%) or rightward (64%) directional bias for initial exploration and thus a behaviour that corresponds to the IVE abnormalities found in neglect patients. No abnormalities were found in the standard neglect tests in any of the groups. The atypical IVE in patients with predominantly left-sided Parkinson's disease should be interpreted in the context of recent concepts of attention postulating that a bias in early spontaneous orientation directed to the ipsilesional hemifield reflects a mild and residual manifestation of hemineglect. Since this subtle orientational bias is less subject to compensation than more conspicuous clinical signs of neglect, sensitivity is higher in IVE testing than in conventional neglect assessments in chronic disorders with subclinical neglect. The present findings contribute a new aspect to the complex picture of cognitive and visuospatial abnormalities in Parkinson's disease. Furthermore our results extend previous knowledge on the mechanisms of neglect and the role of dopamine in the mediation of attention.

Aged↗
PubMed1996

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.

Adult↗
PubMed1995

[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↗
PubMed1995

[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↗
PubMed1991

[Effect of amiodarone on signal-averaged and long-term ECG].

This prospective study examined the influence of long-term amiodarone therapy on the parameters of the signal-averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose, 23 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and high-grade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after 2 months and, subsequently, every 3 months, a resting ECG, a signal-averaged ECG by Simson's method, and Holter monitoring were performed. Compared to the initial measurement, we found a significant increase in the duration of the total filtered QRS complex from an average of 114 +/- 24 ms to 127 +/- 35 ms, while the change in voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone; 10 patients showed a constant late potential, 12 patients had no late potential, and one patient with coronary heart disease developed a new late potential. In the long-term follow-up, we ascertained a relatively high responder rate under amiodarone between 41% and 81%. No relation could be detected between the results of the signal-averaged ECG and those of 24-h Holter monitoring.

Aged↗
PubMed1990

Amiodarone--efficacy and late potentials during long-term therapy.

This prospective study was intended to examine the influence of long-term amiodarone therapy on the parameters of the signal averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose 27 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and highgrade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after two months and subsequently every three months if possible, a resting ECG, a signal averaged ECG by the method of Simson and Holter monitoring were performed. Compared to the initial measurement we found a significant increase in the duration of the total filtered QRS complex, while the change in the voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone. In the long-term follow up Holter monitoring showed a relatively high responder rate of between 46 and 81% under amiodarone. No relation could be detected between the results of the signal averaged ECG and those of 24-h Holter monitoring.

Amiodarone↗