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Biomedical subjects

M B Stern

Publications and source records attributed to M B Stern.

At least 19 recordsLinked to original sources
PubMed1999

Does levodopa accelerate Parkinson's disease?

Therapeutic options for the treatment of Parkinson's disease (PD) have expanded tremendously over the last 5 years, although levodopa remains the gold standard of therapy. A major therapeutic controversy has been the question of levodopa's potential to cause toxic effects on nigrostriatal cells, thus potentiating the progression of the disease. The answer to that question will guide physicians in the timing of levodopa initiation and its dosage. The issue of levodopa toxicity was initially raised because of its potential to cause long term adverse effects (dyskinesias and motor fluctuations), which are not observed in untreated patients. Levodopa-induced toxicity can be related to its potential to produce free radicals, which are known to be toxic to cells, in the process of its conversion to dopamine. In vitro data reveals some evidence of the toxic effect of levodopa although recent studies suggest that levodopa toxicity is dependent on its concentration and can be ameliorated in the presence of glial cells. In vivo data from healthy animals and humans does not convincingly demonstrate levodopa toxicity. There is no evidence of levodopa-induced neurotoxicity in patients with PD. Despite the absence of toxic effect in patients with PD, levodopa can cause long term complications like motor fluctuations and dyskinesias and should be used judiciously in the minimal clinically effective dose. In this article we review evidence for and against levodopa neurotoxicity and the implications of the 'levo-dopa controversy' on clinical practice.

Animals↗
PubMed1997

Parkinson's disease: the case for novel treatment strategies.

Over the past 30 years, significant strides have been made toward improving symptomatic therapy of patients with Parkinson's disease. However, limitations persist, and the incremental improvement each new drug offers a patient yields only a minimal advantage therapeutically. Therefore, to alter meaningfully the natural course of this debilitating disorder, which becomes more prevalent each year in our society, significant novel therapeutic approaches must be tested. Genetic intervention in Parkinson's disease may offer an entirely different method for treating this disease in the future, based not only on symptomatic therapy, but also on neuroprotective and/or neuroregenerative therapy which would alter the natural history of relentless progression.

Antiparkinson Agents↗
PubMed1997

Contemporary approaches to the pharmacotherapeutic management of Parkinson's disease: an overview.

A number of unresolved issues complicate the effective management of patients with Parkinson's disease (PD). Chief among these is the role of neuroprotective versus symptomatic pharmacologic interventions. Until the etiology of PD is further defined, consensus on appropriate management of this illness is unlikely. Clinicians may best serve their patients by taking a pragmatic approach to the treatment of PD that utilizes potentially beneficial interventions in eligible patients. Such an approach would incorporate possible neuroprotective (e.g., selegiline, dopamine agonists, sustained-release levodopa) and dopamine-sparing (e.g., combination levodopa/dopamine agonist therapy) strategies whenever possible while retaining adequate symptomatic control.

Antiparkinson Agents↗
PubMed1996

Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.

Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.

Activities of Daily Living↗
PubMed1995

Olfactory testing as an aid in the diagnosis of Parkinson's disease: development of optimal discrimination criteria.

Since olfactory dysfunction is among the first signs of idiopathic Parkinson's disease (PD), olfactory testing may aid in the early of 'preclinical' diagnosis of this disorder. Indeed, the proportion of early-stage PD patients with olfactory dysfunction appears to be greater than the proportion of early-stage PD patients exhibiting some of the cardinal signs of PD. Because olfactory function varies in the general population and declines with age, empirically-based criteria are needed by the clinician to establish whether the degree of olfactory loss observed in a given patient is concordant with the presence of PD. In this study, we present cutoff criteria for the optimal assessment of olfactory dysfunction in the evaluation of PD. Specifically, we present scores for the University of Pennsylvania Smell Identification Test (UPSIT) that best discriminate between PD patients and age-matched controls. Receiver operating characteristic (ROC) curves, based upon sensitivity and specificity estimates, were computed for three age groups (< or = 60 yrs, 61-70 yrs, and > or = 71 yrs) and scores with highest sensitivity and specificity were determined. Sex- and age-related differences in the test scores were observed, with lower scores occurring for men and for the older patient groups.

Age Distribution↗
PubMed1995

Therapy guided by symptoms for Parkinson's disease.

Low-dose combinations of medications that work in slightly different ways constitute optimal management of Parkinson's disease. Surgical approaches are being perfected for patients who stop responding favorably to pharmacologic treatment.

Humans↗
PubMed1994

Olfactory function in Parkinson's disease subtypes.

Decreased olfactory function commonly occurs in idiopathic Parkinson's disease (PD), regardless of stage, treatment, or duration of disease. In the present study, we sought to determine whether different subtypes of PD, categorized according to well-defined clinical criteria, evidence different degrees of olfactory dysfunction. Significantly different scores on the University of Pennsylvania Smell Identification Test (UPSIT) were present between patients with benign PD and malignant PD (respective means [SD] = 22.51 [8.50] and 17.38 [6.29]) and between tremor-predominant PD and postural instability-gait disorder (PIGD)-predominant PD (23.43 [8.18] versus 17.35 [6.00]). No statistically significant differences in UPSIT scores were observed between young-onset and older-onset PD patients. Women outperformed men in most subtypes examined.

Adult↗
PubMed1993

Reliability of regional cerebral blood flow activation to cognitive tasks in elderly normal subjects.

The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indirect measurement of cortical metabolic activity. The utility of this method in longitudinal clinical studies depends on the stability and reproducibility of resting and activated flow measures. We evaluated CBF in a sample of 16 elderly normal subjects (aged 54-73 years) at rest and during task performance in two sessions separated by an average of 9 weeks. Resting global CBF was lower in the second session, a finding consistent with the known effects of habituation previously reported. Regionally specific activated CBF did not change with repeated measurements. The results provide evidence that the 133Xe technique is reliable and of potential utility in evaluating the effect of the natural course of brain disease, as well as the effects of therapeutic interventions on brain activity.

Aged↗
PubMed1993

Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson's disease.

Olfactory dysfunction occurs in most patients with idiopathic Parkinson's disease (PD). In this study, we sought to determine whether such dysfunction is also present in progressive supranuclear palsy (PSP), a condition which shares a number of motor symptoms with PD and is commonly misdiagnosed as PD. We administered the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability, to 21 PSP patients; 17 also received a forced-choice odor detection threshold test. We compared the olfactory test scores to those obtained from PD patients and normal controls matched to the PSP patients on the basis of age, sex, and smoking habits. Overall, the olfactory function of the PSP patients was markedly superior to that of the PD patients and did not differ significantly from that of the normal controls. There was no association in either the PSP or PD patient groups between (1) the olfactory test scores and (2) measures of motor symptom severity, disease stage, and medication usage. These findings demonstrate that patients with PSP and PD differ markedly in their ability to smell and suggest that olfactory testing may be useful in their differential diagnosis.

Aged↗
PubMed1993

Update on the management of Parkinson's disease.

Parkinson's disease is one of the most common neurologic disorders. Recent advances have shed new light on the nature of the disease process and have led to new strategies for management. This article reviews the biology of Parkinson's disease, the diagnostic approach to patients with parkinsonism, pharmacologic treatments, and practical strategies for managing common clinical problems.

Depression↗
PubMed1993

Parkinson's disease: early diagnosis and management.

Parkinson's disease is a common neurodegenerative disorder affecting approximately 1% of the population over the age of 50 years. There is no known cure for Parkinson's disease, but research gains over the last two decades have been substantial, resulting in improved medications and therapeutic strategies for managing early symptoms and delaying the onset of serious disability. Particularly promising is current research suggesting the possibility of neuroprotective therapies that may ultimately be capable of slowing disease progression. Early and accurate diagnosis is especially important to optimize the benefits of new therapies.

Adaptation, Psychological↗
PubMed1992

Sentence comprehension in Parkinson's disease: the role of attention and memory.

Sentence comprehension is a complex process involving at least attentional, memory, grammatical, and semantic components. We report three experiments designed to evaluate the impairments underlying sentence comprehension difficulties in nondemented patients with Parkinson's disease (PD). In the first experiment, we asked patients to answer simple questions about sentences which varied in terms of grammatical complexity and semantic constraint. We found that PD patients are significantly compromised in their ability to perform this task. Their difficulties became more prominent as grammatical complexity increased, but they were significantly assisted by semantic constraints that limited possible interpretations of a sentence. Analyses of individual patient profiles revealed heterogeneous performance across the group of PD patients and somewhat inconsistent performance for patients across testing sessions. In the second experiment, we tested the possibility that patients' heterogeneous performance on the sentence comprehension task is due to an impairment in memory or attention, cognitive domains known to be compromised in some PD patients. Although PD patients and control subjects differed on one memory measure, there were no significant correlations between attention and memory performance and the results of the sentence comprehension task. In the final experiment, we manipulated the sentences used in the first experiment in a fashion that stressed the need for memory and attention in a sentence. The results indicated that PD patients are significantly compromised in their ability to attend to certain critical grammatical features of a sentence. A regression analysis identified specific grammatical, semantic, and attentional mechanisms as significant contributors to PD patients' overall sentence comprehension, accounting for over 97% of the variance in their performance. We conclude that there are multiple sources of cognitive difficulty underlying PD patients' sentence comprehension impairment.

Aged↗
PubMed1992

Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson's disease.

Decreased olfactory function is among the first signs of idiopathic Parkinson's disease (PD). Whether such dysfunction is present to the same degree on both sides of the nose, however, is unknown. Furthermore, whether the deficit results from or is influenced by anti-Parkinsonian medications has not been definitely established. Odour identification ability was evaluated on the left and right sides of the nose in 20 early-stage untreated PD patients, 20 early-stage treated PD patients, and 20 controls. In all cases, the PD related olfactory dysfunction was bilateral and no difference was observed between the test scores of patients taking or not taking drugs for PD. Although asymmetries of unsystematic direction were present in the test scores of some PD patients, similar asymmetries were observed in the controls and the asymmetries were not related to the side of the major motor dysfunction. As in earlier work, no relation was present between the olfactory test scores and the degree of tremor, rigidity, bradykinesia, or gait disturbance at the time of testing. These findings indicate that the olfactory dysfunction of early stage PD is robust, typically of the same general magnitude on both sides of the nose, and uninfluenced by anti-Parkinsonian medications.

Age Factors↗