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Biomedical subjects

C G Goetz

Publications and source records attributed to C G Goetz.

At least 109 records · Page 6Linked to original sources
PubMed1998

Influence of COMT inhibition on levodopa pharmacology and therapy.

Catechol O-methyltransferase (COMT) is an important enzyme that is linked directly to therapy with levodopa. Considering the demonstrated mechanism of action and pharmacologic profiles of COMT inhibitors, it is reasonable to hypothesize that these agents would improve the disability associated with Parkinson's disease. Two basic classes of COMT inhibitors are being studied in patients with PD: those that act exclusively extracerebrally or peripherally (e.g., entacapone) and those that cross the blood-brain barrier (e.g., tolcapone). With COMT inhibition, greater peripheral bioavailability of levodopa occurs in humans without an enhancement of peak plasma levels. It is reasonable to suggest that COMT inhibition will be associated with prolonged effects of levodopa in PD, without increased peak dose toxicity in the form of dyskinesias and hallucinations.

Animals↗
PubMed1998

Early dopaminergic drug-induced hallucinations in parkinsonian patients.

OBJECTIVE: To characterize patients who develop hallucinations early in the course of dopaminergic therapy for Parkinson's disease (PD) and contrast them with patients developing hallucinations after chronic drug treatment. METHODS: Parkinsonian patients who met diagnostic criteria for PD, experienced hallucinations, had a detailed hallucination interview at the onset time of their first hallucination, and had a 5-year clinical follow-up or an autopsy in those 5 years were identified and divided into two groups for comparison: 12 patients who developed early hallucinations within 3 months of starting levodopa therapy and 58 PD patients who developed hallucinations after 1 year of dopaminergic therapy. We contrasted the quality, content, diurnal nature, and emotional elements of the hallucinations, as well as the 5-year follow-up data on diagnosis, disease course, community home or nursing home outcome, and mortality. RESULTS: Both groups experienced a predominance of visual hallucinations, visions of people and animals, and vivid colors and definition. Features distinctive to the early onset hallucinating patients included visions that persisted in daytime as well as nighttime, frightening content with paranoia, and accompanying nonvisual hallucinations, either auditory, olfactory, tactile, or combinations thereof. At the 5-year follow-up, none of the early onset hallucinators had PD as their sole disorder. Four of the 12 had an underlying psychiatric illness that included hallucinations or psychosis preceding their parkinsonism by several years. In the other eight patients at the 5-year follow-up, their parkinsonism evolved to include additional signs that were no longer consistent with PD. The primary diagnoses were diffuse Lewy body disease and Alzheimer's disease (AD) with extrapyramidal signs. Patients with early drug-induced hallucinations had significantly greater placement to nursing homes and greater mortality. CONCLUSIONS: Early onset drug-related hallucinations are not typical of PD. Their presence should signal an investigation of two alternative diagnoses, either a comorbid psychotic illness (often unrevealed by the patient initially) or an evolving parkinsonism-plus syndrome.

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PubMed1997

What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study.

BACKGROUND: The presentation of symptoms for multiple system atrophy (MSA) varies. Because there are no specific markers for its clinical diagnosis, the diagnosis rests on the results of the neuropathologic examination. Despite several clinicopathologic studies, the diagnostic accuracy for MSA is unknown. OBJECTIVES: To determine the accuracy for the clinical diagnosis of MSA and to identify, as early as possible, those features that would best predict MSA. DESIGN: One hundred five autopsy-confirmed cases of MSA and related disorders (MSA [n=16], non-MSA [n=89]) were presented as clinical vignettes to 6 neurologists (raters) who were unaware of the study design. Raters identified the main clinical features and provided a diagnosis based on descriptions of the patients' first and last clinic visits. METHODS: Interrater reliability was evaluated with the use of kappa statistics. Raters' diagnoses and those of the primary neurologists (who followed up the patients) were compared with the autopsy-confirmed diagnoses to estimate the sensitivity and positive predictive values at the patients' first and last visits. Logistic regression analysis was used to determine the best predictors to diagnose MSA. RESULTS: For the first visit (median, 42 months after the onset of symptoms), the raters' sensitivity (median, 56%; range, 50%-69%) and positive predictive values (median, 76%; range, 61%-91%) for the clinical diagnosis of MSA were not optimal. For the last visit (74 months after the onset of symptoms), the raters' sensitivity (median, 69%; range, 56%-94%) and positive predictive values (median, 80%; range, 77%-92%) improved. Primary neurologists correctly identified 25% and 50% of the patients with MSA at the first and last visits, respectively. False-negative and -positive misdiagnoses frequently occurred in patients with Parkinson disease and progressive supranuclear palsy. Early severe autonomic failure, absence of cognitive impairment, early cerebellar symptoms, and early gait disturbances were identified as the best predictive features to diagnose MSA. CONCLUSIONS: The low sensitivity for the clinical diagnosis of MSA, particularly among neurologists who followed up these patients in the tertiary centers, suggests that this disorder is underdiagnosed. The misdiagnosis of MSA is usually due to its confusion with Parkinson disease or progressive supranuclear palsy, thus compromising the research on all 3 disorders.

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PubMed1997

Teaching tape for the motor section of the Toronto Western Spasmodic Torticollis Scale.

The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) assesses the character and severity of cervical dystonia (CD). We developed a teaching tape of the TWSTRS scoring for the motor symptoms of CD. The tape provides investigators with visual representations of each component of the motor section of the TWSTRS as agreed upon by three independently scoring raters. The rate of agreement for the nondichotomous components was always significant, with a Kendall's coefficient of concordance W ranging between 0.98 and 0.76 (p < 0.01 for all measures). For the two dichotomous components, a weighted kappa coefficient was also significant at 0.86 for lateral shift and 0.89 for sagittal shift (p < 0.01 for both measures). Scale deficiencies identified by the raters were an explicit definition of midline for assessment of range of motion, the absence of a separate scoring category assessing dystonic tremor, and the specification of duration for the effect of sensory tricks. These observations should be taken into account in future revisions of the TWSTRS and in refinements of other rating scales for CD.

Dystonia↗
PubMed1997

Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in Parkinson's disease.

Patient on-off diaries are used in clinical trials, but a method to assure agreement between patient and examiner has never been developed. We tested whether a patient-teaching tape increased the rate of agreement between patient diary ratings and simultaneous neurologic assessment by a trained professional. A total of 32 consecutive patients who had Parkinson's disease with motor fluctuations independently completed a 4-h on-off diary (nine ratings) at the same time as an examiner. Those with < 80% agreement with the examiner (n = 20) were randomized to view either a training tape that showed motor fluctuations (experimental group) or-another videotape of general patient educational material (control group). All patients then underwent the same 4-h assessment of motor fluctuations. To test for long-term retention, they returned 1 month later and, without reviewing the videotape, underwent a final 4-h correlation assessment. After the training tape, the experimental group showed significant improvement, whereas the control group showed no improvement. Furthermore, another month later, the improvement in the experimental group was retained. Based on these findings, we suggest that future clinical trials assessing motor fluctuations incorporate this tape into their basic methodology.

Activities of Daily Living↗
PubMed1997

New strategies with dopaminergic drugs: modified formulations of levodopa and novel agonists.

Most new pharmacological therapies in Parkinson's disease focus on the dopaminergic system. Drugs that enhance dopaminergic function fall into three primary categories: amino acid precursors to dopamine, agonists that stimulate dopamine receptors, and enzyme antagonists that prevent the metabolism of dopamine and hence permit more or prolonged neurotransmitter activity; the first two are discussed below. Within the first category, levodopa is the amino acid precursor to dopamine, and a number of modifications in its formulation have been developed to enhance dopaminergic activity. In the area of agonists, new agents pramipexole, ropinerole, and cabergoline have recently been developed to complement the currently available bromocriptine and pergolide, and these new drugs may be released in the United States.

Antiparkinson Agents↗
PubMed1997

Dopaminergic transplants in patients with Parkinson's disease: neuroanatomical correlates of clinical recovery.

For the past 15 years, patients with Parkinson's disease have participated in clinical trials evaluating the efficacy of intrastriatal dopamine transplants. Principally, two donor tissues have been employed, the chromaffin cells of the adrenal medulla and fetal ventral mesencephalon. The clinical response following each type of transplant has been variable. In general, the magnitude and the duration of the clinical response is greater with fetal dopaminergic neurons than with adrenal medullary grafts. Postmortem studies of patients receiving adrenal medullary grafts or fetal nigral implants provide a neuroanatomical framework for the clinical response. Adrenal grafts survive poorly following implantation into the striatum, but they are capable of inducing sprouting of host-derived fibers within a the caudate nucleus. In contrast, robust survival of fetal nigral implants can be achieved within the human brain which can provide extensive reinnervation to the parkinsonian striatum. These findings are strikingly similar to what has been seen in rodent and nonhuman primate models of PD. This paper describes the neuroanatomical correlates of dopamine brain grafting in humans and elucidates the pattern of changes seen in dopaminergic systems which are associated with clinical benefit.

Adrenal Medulla↗
PubMed1997

Effect of stereotaxic intrastriatal cografts of autologous adrenal medulla and peripheral nerve in Parkinson's disease: two-year follow-up study.

Studies in nonhuman primates with experimental parkinsonism have shown that intrastriatal cografts of autologous adrenal medulla and peripheral nerve yield greater behavioral improvement and graft survival than do adrenal medulla grafts alone. To test these observations, five patients with advanced Parkinson's disease were selected to receive unilateral intrastriatal adrenal medulla-intercostal nerve cografts. They were evaluated using the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol. Three of these patients also underwent quantitative motor testing for the measurement of upper limb bradykinesia (movement time; MT). Following right flank adrenalectomy, cografts consisting of small fragments of adrenal medullary tissue and minced intercostal nerve were stereotaxically implanted into three targets in the right striatum using computerized tomography guidance. Surgery was uneventful and postoperative magnetic resonance imaging revealed accurate placement of the grafts. No morbidity was encountered. Results of 24 months of clinical and quantitative motor assessments postoperatively are reported. Total UPDRS motor scores in the "off" state improved from a mean preoperative score of 39.5 to 32.1 at 3, 29.7 at 6, 27.6 at 9, 28.5 at 12, 31.4 at 18, and 26.5 at 24 months after surgery. Total timed motor test scores during the "off" state improved 17.9% at 6, 23.3% at 9, 18.2% at 12, 38.2% at 18, and 34.9% at 24 months postoperatively compared to baseline. Movement time showed statistically significant improvement (repeated measures ANOVA, P < 0.05) in the left arm (contralateral to surgery) in all three patients tested. These results indicate that stereotaxic intrastriatal implantation of autologous adrenal medulla-peripheral nerve cografts can be performed safely and clinical improvement from this procedure is sustained for a period of 24 months. The clinical improvement was paralleled by improvement in objective, quantitative motor testing.

Adrenal Medulla↗
PubMed1997

Tourette syndrome. Clinical rating and quantitative assessment of tics.

An adequate rating scale for the measurement of tic severity must account for the multiple motor and phonic tics that increase and decrease over time. Available rating scales for Tourette syndrome have used historical information, direct observation, or both. Videotapes provide an objective means to quantify tics over time in a controlled environment. Videotapes also can be viewed multiple times for careful review of tic frequency and distribution. A unified rating scale, which integrates all elements of tic assessment is being developed, but is not currently available.

Humans↗
PubMed1997

Intact mirror-tracing and impaired rotary-pursuit skill learning in patients with Huntington's disease: evidence for dissociable memory systems in skill learning.

Skill learning in early-stage Huntington's disease (HD) patients was compared with that of normal controls on 2 perceptual-motor tasks, rotary pursuit and mirror tracing. HD patients demonstrated a dissociation between impaired rotary-pursuit and intact mirror-tracing skill learning. These results suggest that different forms of perceptual-motor skill learning are mediated by separable neural circuits. A striatal memory system may be essential for sequence or open-loop skill learning but not for skills that involve the closed-loop learning of novel visual-response mappings. It is hypothesized that working memory deficits in HD resulting from frontostriatal damage may account broadly for intact and impaired long-term learning and memory in HD patients.

Adult↗
PubMed1997

Jean-Martin Charcot and Silas Weir Mitchell.

Although Charcot and Mitchell only met once or possibly twice in Paris (1873 and 1875), they interacted in multiple ways to influence one another's research and the development of nineteenth century neurology. Charcot strongly relied on, and openly credited, Mitchell's important contributions on the fragility of bones in locomotor ataxia when he postulated his own historic concepts on neuropathic arthropathies (Charcot joints). Mitchell likewise referred to Charcot in his texts and manuscripts, although his comments were not always complementary. Most notably, Mitchell publicly criticized Charcot for wrongfully claiming precedence over Americans (i.e., Mitchell himself) in the development of isolation therapy. The two men shared many specific neurologic interests, especially the effects of trauma and disorders affecting women, including hysteria. In the development of clinical neurology as a new scientific field, Charcot and Mitchell were both strong empiricists who distrusted theory but believed that clinical medicine, and specifically neurology, required continued infusion of new data from the laboratory sciences. Both men were exemplary teachers, Mitchell primarily a preceptor and supervisor of doctors outside the university system and Charcot the first European professor of clinical neurology and head of the celebrated School of the Salpêtrière.

France↗
PubMed1997

What are the obstacles for an accurate clinical diagnosis of Pick's disease? A clinicopathologic study.

Several studies have evaluated the reliability and validity of the clinical diagnosis of Alzheimer's disease (AD) using well-defined neuropathologic criteria, but none has attempted to evaluate the diagnostic accuracy of Pick's disease. We determined the accuracy of the clinical diagnosis of Pick's by presenting 105 autopsy-confirmed cases of Pick's (n = 7) and related disorders (non-Pick's, n = 98) as clinical vignettes in randomized order to six neurologists who were unaware of the autopsy findings. The group of raters had moderate to fair agreement for the diagnosis of Pick's as measured by the kappa statistics. The sensitivity for the diagnosis of Pick's for the first visit (mean, 53 months after onset) and last visit (mean, 78 months after onset) was low (range, 0 to 71%), but specificity was near-perfect. Median positive predictive values at both visits were 83 to 85%. False-negative misdiagnoses mainly involved AD. False-positive diagnoses were rare and occurred with corticobasal degeneration (first visit) and with dementia with Lewy bodies (last visit). Pick's was also misdiagnosed by primary neurologists. The best clinical predictors for the early diagnosis of Pick's included "frontal" dementia, early "cortical" dementia with severe frontal lobe disturbances, absence of apraxia, and absence of gait disturbance at onset. However, the first neurologic evaluation in some of the Pick's cases took place in advanced stages of the disease. Our findings suggest that this disorder is underdiagnosed in clinical practice. Although the low sensitivity for the clinical diagnosis of Pick's is disappointing, our data suggest that when clinicians suspect Pick's, their diagnosis is almost always correct. Absence of awareness of the main features of this disorder and of specificity of the frontal lobe syndrome may partially explain the low detection of Pick's disease.

Aged↗
PubMed1997

Metric properties of nurses' ratings of parkinsonian signs with a modified Unified Parkinson's Disease Rating Scale.

We evaluated the ability of nurse clinicians to assess parkinsonian signs in older persons with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). After completing a structured training protocol, three nurse clinicians and a neurologist with expertise in movement disorders administered a modified UPDRS to 75 older persons. The nurses repeated the assessment about 3 weeks later. Inter-rater agreement and short-term temporal stability were estimated for each item, the total modified UPDRS score, and for summary measures of bradykinesia, postural reflex impairment, rigidity, and tremor, and a global parkinsonian sign score. We performed our assessment in Catholic religious communities in the Chicago area, using consecutive subjects at four communities participating in the Religious Orders Study, a longitudinal, clinical-pathologic study of older persons. Our results showed that nurses were not a significant source of variability, with intraclass correlations exceeding 0.97 for all items, and they showed good to excellent agreement with the neurologist for most modified UPDRS items. Correlations between nurses and neurologist exceeded 0.90 for the total modified UPDRS, ranged from 0.76 to 0.95 for the four parkinsonian domain scores, and exceeded 0.90 for the global parkinsonian sign score. Nurses showed fair to good agreement with themselves over the 3-week interval for most modified UPDRS items. Correlations over the 3-week interval exceeded 0.90 for the total modified UPDRS score, ranged from 0.70 to 0.95 for the four domain scores, and exceeded 0.90 for the global parkinsonian sign score. Ratings of parkinsonian signs by nurse clinicians corresponded closely to those of a neurologist with expertise in movement disorders and showed good inter-rater agreement and temporal stability. With appropriate training, nurse clinicians can reliably administer the modified UPDRS.

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