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Biomedical subjects

E Siemers

Publications and source records attributed to E Siemers.

At least 19 recordsLinked to original sources
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2000

Rate of functional decline in Huntington's disease. Huntington Study Group.

OBJECTIVE: To determine the rate of functional decline in a large cohort of patients with Huntington's disease (HD) followed at 43 sites by the Huntington Study Group (HSG). METHODS: The annual rate of functional decline was measured using the Total Functional Capacity Scale (TFC) and the Independence Scale (IS) in 960 patients with definite HD followed prospectively for a mean of 18.3 months. All patients were rated with the Unified Huntington's Disease Rating Scale (UHDRS). Sample size calculations for hypothetical clinical trials were calculated. RESULTS: A factor analysis of the UHDRS at baseline yielded 15 factors accounting for 77% of the variance. The TFC score declined at a rate of 0.72 units/year (standard error [SE] 0.04) and the IS score declined at a rate of 4.52 units/year (SE 0.23). Lower TFC score at baseline, indicating more severe impairment, was associated with less rapid annual decline in TFC score, perhaps reflecting the floor effect of the scale. The annual rate of decline for 575 patients with baseline TFC scores of 7 to 13 was 0.97 (SE 0.06), was 0.38 (SE 0.08) for 270 patients with baseline TFC scores of 3 to 6, and was 0.06 (SE 0.1) for 101 patients with TFC scores of 0 to 2. In multivariate analysis (n = 960), longer disease duration and better cognitive status at baseline were associated with a less rapid rate of decline in TFC score, whereas depressive symptomatology was the only factor associated with more rapid decline on the IS score. Age at onset of HD, sex, weight, and education did not affect decline on either score. CONCLUSIONS: The comparable rates of decline on the TFC and the IS scores with other published studies suggest that these estimates of functional decline are representative of HD patients who are evaluated at HSG research sites. In longitudinal analysis, longer disease duration and better neuropsychological performance at baseline were associated with a less rapid rate of decline in TFC score, whereas depressive symptomatology at baseline was associated with a more rapid decline in the IS score. These rates of functional decline and the covariates that modify them should be considered in estimating statistical power and designing future therapeutic trials involving HD patients with early or moderately severe disease.

Activities of Daily Living↗
PubMed2000

Confirmation of subtle motor changes among presymptomatic carriers of the Huntington disease gene.

OBJECTIVE: To confirm that subtle changes in motor function and reaction time are present in presymptomatic individuals carrying the expanded Huntington disease (HD) allele. DESIGN: A case-control, double-blind study comparing presymptomatic HD gene carriers (PSGCs) and nongene carriers (NGCs) at risk for HD. SETTING: The Department of Medical and Molecular Genetics at a general clinical research center in a midwestern city. PARTICIPANTS: Two hundred sixteen individuals at risk for HD who were asymptomatic by self-report and who did not have manifest HD on results of clinical examination, including PSGCs (n = 61) and NGCs (n = 155). MEASURES: Molecular testing was used to determine the number of CAG repeats in the HD gene. A quantified neurologic examination and a battery of physiological measures of central nervous system function measuring speed of movement and reaction time were administered. RESULTS: On neurologic examination, the PSGCs exhibited significantly more definite or possible abnormalities than NGCs for overall oculomotor function, saccade velocity, optokinetic nystagmus, chorea of the extremities, and dystonia of the extremities (P<.05). The PSGCs also had significantly slower performance for auditory reaction time, visual reaction time, visual reaction time with decision, movement time, movement time with decision, and button-tapping time, compared with the NGCs (P<.05). CONCLUSIONS: Subtle changes in motor function, speed of movement, and reaction time are present in HD gene carriers who do not exhibit definite choreiform movements and who do not have sufficient signs to make a clinical diagnosis of HD. In addition, a trend toward slower speed of movement and reaction time was observed among this population as their neurologic abnormalities increased.

Adult↗
PubMed2000

Subtle changes among presymptomatic carriers of the Huntington's disease gene.

OBJECTIVES: To compare the neurological and psychometric characteristics of presymptomatic gene carriers and non-gene carriers who are at risk for developing Huntington's disease so as to characterise early signs of disease and to identify markers of neurological function that could be used to assess the impact of experimental therapies on the progression of disease, even among those who are clinically presymptomatic. METHODS: A sample of people at risk for Huntington's disease was genotyped and evaluated using subscales of the Wechsler adult intelligence scale-revised (WAIS-R), a quantified neurological rating scale, and computerised physiological measures including speed of movement and reaction time. RESULTS: Genotyping and clinical examination determined that 171 participants were presymptomatic gene carriers (PSGCs) and 414 participants were non-gene carriers (NGCs). The PSGCs performed significantly worse when compared with the NGCs on the digit symbol, picture arrangement, and arithmetic subscales of the WAIS-R (p<0.02) and for the physiological measures: button tapping, auditory reaction time, visual reaction time with decision, and movement time with and without decision (p<0.05). Although no PSGCs had sufficient neurological findings to warrant a diagnosis of Huntington's disease on clinical examination, the PSGCs had more frequent possible or definite abnormality for oculomotor function, chorea, muscle stretch reflexes, gait, and station stability, and rapid alternating movements (p</=0.02). CONCLUSIONS: Among Huntington's disease gene carriers, subtle cognitive and motor deficits precede the onset of sufficient neurological abnormality to warrant a clinical diagnosis of Huntington's disease.

Adult↗
PubMed2000

Eye movements in Parkinson's disease: before and after pallidotomy.

PURPOSE: To evaluate the effects of unilateral, stereotactic, posteroventral pallidotomy on saccadic eye movements in patients with Parkinson disease (PD). METHODS: Eye movements of 31 patients with moderate to advanced PD were recorded with an infrared system 1 month before and 3 months after pallidotomy. Two kinds of saccade tasks were used: saccade tasks for eliciting visually guided saccades and saccade tasks for eliciting internally mediated saccades (memory-guided, predictive, and anti-saccades). Latency, accuracy, peak velocity, and other parameters of saccades were evaluated. RESULTS: Internally mediated saccades were more impaired in patients with advanced PD compared with those with moderate PD. Pallidotomy did not affect visually guided saccades. After pallidotomy, the peak saccadic velocity of internally mediated saccades decreased. CONCLUSIONS: Hence, although pallidotomy has led to improvements in other motor functions, none were observed in saccadic responses. Rather, several modest decrements, below the level of clinical significance and all in internally mediated saccades, were observed.

Aged↗
PubMed1999

Longitudinal cognitive and motor changes among presymptomatic Huntington disease gene carriers.

OBJECTIVE: To determine whether longitudinal changes in cognitive and motor function can be detected among clinically presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN: A longitudinal, case-control, double-blind study comparing presymptomatic gene carriers and non-gene carriers at risk for HD examined an average of 3.7 years apart. SETTING: The Department of Medical and Molecular Genetics at a general clinic research center in Indianapolis, Ind. PARTICIPANTS: A sample of 43 at-risk individuals consisting of presymptomatic gene carriers (n = 12) and non-gene carriers (n = 31). MEASURES: Huntington disease gene status was determined by molecular testing of the HD gene. Subscales from the Wechsler Adult Intelligence Scale-Revised and a quantified neurologic rating scale were administered. RESULTS: Scores on the digit symbol subscale of the Wechsler Adult Intelligence Scale-Revised (P<.05) and 2 neurologic variables-optokinetic nystagmus (P<.01) and rapid alternating movements (P<.005)-declined more rapidly among presymptomatic gene carriers than among non-gene carriers. At follow-up examination, compared with nongene carriers, presymptomatic gene carriers had significantly lower scores on the digit symbol subscale (P = .02) and for 4 neurologic variables-rapid alternating movements (P<.005), optokinetic nystagmus (P<.001), overall ocular movements (P<.02), and chorea of the trunk (P<.02). CONCLUSIONS: Psychomotor speed, optokinetic nystagmus, and rapid alternating movements demonstrated significant decline early in the pathological process of HD. These results suggest that subtle worsening of psychomotor, oculomotor, and motor functions occurs before the onset of signs sufficient to make a clinical diagnosis in individuals who have inherited the HD allele.

Adult↗
PubMed1999

Multiple system atrophy.

MSA is a complex disorder, with regard to its pathology and cause as well as its clinical diagnosis and treatment. Although a number of clinical treatments may improve quality of life for these patients, given the widespread pathology present, symptomatic treatment, particularly that involving neurotransmitter replacement, is likely to remain difficult. Truly effective treatment for these patients is likely to depend on an understanding of the underlying pathogenic mechanisms and methods to halt or reverse disease progression. A firm understanding of the classification of these disorders is the first step to understanding the relevant pathogenic mechanisms. The finding of intracytoplasmic glial inclusion bodies provides a compelling piece of evidence that SND, OPCA, and SDS do, in fact, belong to one nosologic entity. These inclusions do not seem to be present in familial cases of OPCA; thus, they may provide a means to improve diagnostic specificity as well as sensitivity. With the ability to define clearly the entity of MSA, an understanding of the pathophysiology can be developed along with other degenerative neurologic diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease.

Brain↗
PubMed1997

Focal dystonia after chemotherapy: a case series.

Dystonia is a rare neurologic disorder of the basal ganglia presenting with involuntary twisting or turning spasm of muscles. Movements localized to the face, eyes, or neck generally present during late adulthood. Cranial dystonia is usually idiopathic but may be caused by trauma or medications. Of 148 patients with focal dystonia referred to Indiana University over four years, four women had the onset of face and neck symptoms eight days to 34 months after completing treatment with chemotherapy alone or combined with radiation therapy. Two patients were treated with 5-FU, one received doxorubicin and one was treated with both. Both drugs have been associated with transient parkinsonism, but no chemotherapeutic medications have been reported to cause dystonia. Three patients remain free of demonstrable malignancy. A possible association of chemotherapy and focal dystonia has not been previously described.

Adenocarcinoma↗
PubMed1996

Motor changes in presymptomatic Huntington disease gene carriers.

OBJECTIVE: To determine whether changes in motor function and reaction time are present in presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN: A case-control, double-blind study comparing asymptomatic at-risk subjects, with or without the HD allele, and subjects clinically determined to have early manifest HD. SETTING: The Department of Medical and Molecular Genetics at Indiana University School of Medicine, Indianapolis. PARTICIPANTS: We studied 383 patients at risk for HD. Each subject was asymptomatic by self-report. MEASURES: Genotype for the HD allele was determined by polymerase chain reaction testing. A battery of 8 physiological tests measuring speed of movement and reaction time was performed with a computer-driven system. RESULTS: Following neurologic examination, 17 of the 120 gene carriers (GCs) had symptoms sufficient for a clinical diagnosis of manifest HD. The remaining 103 GCs were designated presymptomatic GCs. When the non-GCs were compared with the presymptomatic GCs (1-way analysis of covariance and the Fisher protected t test), results on 3 of the 8 physiological tests--movement time, movement time with decision, and auditory reaction time--were different. Additionally, the number of trinucleotide (CAG) repeats significantly correlated with test performance for movement time with decision and visual reaction time with decision when both the entire group of GCs and the presymptomatic GCs alone were considered. CONCLUSION: These results suggest that subtle subclinical changes in motor function are present in presymptomatic individuals who have inherited the HD allele.

Adult↗
PubMed1995

Cognitive scores in carriers of Huntington's disease gene compared to noncarriers.

Huntington's disease (HD) is a progressive neurodegenerative disorder recently shown to be due to an excess number of CAG trinucleotide repeats in the 5' translated region of chromosome 4. One of the cardinal features of HD is cognitive decline. While mental deterioration is obvious later in the disease course, the time of its onset is difficult to determine precisely. A sample of at-risk individuals without signs or symptoms of HD by self-report was studied. The Wechsler Adult Intelligence Test--Revised and a neurological rating scale were administered. The genotypes of 394 individuals were then determined by polymerase chain reaction testing. On all portions of the WAIS-R test, the mean score of the HD gene carriers was lower than that of the noncarriers. Scores on two of the performance subtests, the digit symbol and the picture arrangement, were significantly different in the two groups, even after the scores from all gene carriers who were diagnosed as affected based on their neurological motor examination were removed. The scores for the gene carriers on the various subtests were negatively correlated with the number of CAG repeats in the expanded HD allele. Such a relationship was not seen with the normal alleles of the noncarriers. Taken together, our results suggest that a deficit in cognitive function is an early finding of HD and that in this patient population, the degree of cognitive deficit is proportional to the number of CAG repeats in the HD allele.

Adult↗
PubMed1995

Quantification of thyrotropin-releasing hormone changes and serotonin content changes following graded spinal cord injury.

Thyrotropin-releasing hormone (TRH) and serotonin (5-HT) are well known as neurotransmitters of descending bulbo-spinal tracts. 5-HT uptake caudal to (5-HT decreased) graded spinal lesions has been measured in rats and dogs and significantly correlated with the degree of cord injury. We studied 5-HT content via high-pressure liquid chromatography and radioimmunoassay measurements of TRH in dog spinal cord, both rostral and caudal, to 6 week T6 spinal transection (T) (n = 7) or T6 hemisections (H) (n = 7). Sham controls (n = 7) were used. Mean 5-HT content values were (pmole/mg): rostral sham 1.25 +/- 0.02, caudal sham 1.35 +/- 0.17, rostral T 2.65 +/- 0.36, caudal T 0.19 +/- 0.06, rostral H 2.1 +/- 0.22, and caudal H 1.0 +/- 0.31. A significant decrease in 5-HT caudal to transection versus control (P < 0.001) was seen. A trend for decreased 5-HT caudal to hemisection versus control (P < 0.1) was also seen. Mean TRH levels (pg/mg protein) were: rostral sham 40.02 +/- 18.47, caudal sham 30.61 +/- 10.03, brainstem sham 18.9 +/- 5.13, rostral T 52.4 +/- 21.34, caudal T 3.52 +/- 1.87, brainstem T 19.25 +/- 4.11, rostral H 43.45 +/- 18.61, caudal H 14.24 +/- 5.7, and brainstem H 21.89 +/- 1.23. Significant decreases for caudal TRH transection versus controls (P < 0.001) and for caudal TRH hemisection versus controls (P < 0.02) were seen. A significant difference between caudal hemisection and caudal transection TRH levels (P < 0.001) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Recent progress in the treatment of Parkinson's disease.

Because of the number of different types of anti-Parkinsonian medications, a number of options in the treatment of PD are now available. Each patient's medication regimen should be individualized. Many of the medication choices are made based on the stage of the disease. For patients who have newly diagnosed PD, and who are on no medications, treatment with deprenyl should be strongly considered. While some controversy remains concerning its possible slowing of the rate of disease progression, there is no evidence to suggest that its use is detrimental. It is generally well tolerated in patients with early disease. These factors must be weighed against the cost of the medication, and the fact that little if any therapeutic effect is seen in most patients who are not being treated with LD. A useful analogy when considering this issue is the prophylactic use of aspirin for cerebrovascular or cardiovascular disease. Newly diagnosed patients requiring treatment, who have tremor as their only symptom or their most prominent symptom, may be given an anticholinergic medication. Patients who have significant bradykinesia, rigidity or gait disturbance can be given amantadine. A combination of these two medications may be useful, and a combination of deprenyl with an anticholinergic drug or amantadine may provide excellent relief of early symptoms. At some point, most patients' symptoms progress such that treatment with LD is considered. Given its possible, but unproven, acceleration of the rate of disease progression, this decision should be weighed carefully. In a relatively young patient who may be treated for many years, a dopamine receptor agonist can be initiated without LD therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amantadine↗
PubMed1992

[PASS: a community, system-related program for occupational rehabilitation of chronic psychiatric patients in competitive employment].

Notwithstanding considerable success, the concepts currently applied by vocational rehabilitation workshops for persons with chronic mental illness are deemed open to criticism in some respects. Presented is the PASS programme, developed on the basis of more than two decades of experience with the clinic's own rehabilitation workshop. The greater part of the five-phase programme no longer occurs within the workshop but is spent at training workplaces with regional firms. A mobile rehabilitation team does not only support the patients at their training facilities but also their colleagues and immediate superiors, who have been prepared for their forthcoming tasks by psychoeducational information meetings. These community-based, ecological system-related aspects of the programme are complemented by repetitive social skills training and group work with relatives. Assessments carried out in each phase provide important decision-making data for programme development and render its scientific evaluation possible. Our experience so far demonstrates the possibility of recruiting enterprises to provide training places.

Activities of Daily Living↗
PubMed1991

Profile of patients enrolled in a new movement disorder clinic.

To assess the need for a regional expertise in movement disorders, the numbers of patients, clinic visits, and medication changes for a new movement disorder clinic were recorded. During 3 1/2 years, 355 patients were seen, with 1,329 clinic visits. Idiopathic Parkinson's disease was the most common diagnosis, comprising 36% of the population, followed by dystonia (17%), tremor (12%), parkinsonism (i.e., Parkinson's plus syndromes, drug-induced parkinsonism, etc.) (10%), chorea (10%), Tourette's syndrome (6.5%), and tardive dyskinesia (3.4%). Distribution of follow-up visits was similar, with Parkinson's disease (52%) being most frequent and Tourette's syndrome (3.1%) least frequent. The relative utilization of medical care by each patient group was assessed by determining the number of medication changes and the number of clinic visits per follow-up year. No differences in these measures were found using a one-way analysis of variance. Of the Parkinson's disease patients, 67% had Hoehn and Yahr stages III-IV and 77% of the clinic visits were made by this subgroup. When considered in light of the prevalence of each of the diseases, these data show a need for an expertise in movement disorders for a population base of the size we have served.

Cross-Sectional Studies↗