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Biomedical subjects

Christopher G Goetz

Publications and source records attributed to Christopher G Goetz.

At least 55 records · Page 3Linked to original sources
PubMed2003

Parkin mutations and susceptibility alleles in late-onset Parkinson's disease.

Parkin, an E2-dependent ubiquitin protein ligase, carries pathogenic mutations in patients with autosomal recessive juvenile parkinsonism, but its role in the late-onset form of Parkinson's disease (PD) is not firmly established. Previously, we detected linkage of idiopathic PD to the region on chromosome 6 containing the Parkin gene (D6S305, logarithm of odds score, 5.47) in families with at least one subject with age at onset (AAO) younger than 40 years. Mutation analysis of the Parkin gene in the 174 multiplex families from the genomic screen and 133 additional PD families identified mutations in 18% of early-onset and 2% of late-onset families (5% of total families screened). The AAO of patients with Parkin mutations ranged from 12 to 71 years. Excluding exon 7 mutations, the mean AAO of patients with Parkin mutations was 31.5 years. However, mutations in exon 7, the first RING finger (Cys253Trp, Arg256Cys, Arg275Trp, and Asp280Asn) were observed primarily in heterozygous PD patients with a much later AAO (mean AAO, 49.2 years) but were not found in controls in this study or several previous reports (920 chromosomes). These findings suggest that mutations in Parkin contribute to the common form of PD and that heterozygous mutations, especially those lying in exon 7, act as susceptibility alleles for late-onset form of Parkinson disease.

Adolescent↗
PubMed2003

A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease.

Thirty-four patients with advanced Parkinson's disease participated in a prospective 24-month double-blind, placebo-controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinson's Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect (p = 0.244). Patients in the placebo and one-donor groups deteriorated by 9.4 +/- 4.25 and 3.5 +/- 4.23 points, respectively, whereas those in the four-donor group improved by 0.72 +/- 4.05 points. Pairwise comparisons were not significant, although the four-donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients (p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty-six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication ("off"-medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.

Adult↗
PubMed2003

Coping strategies for visual hallucinations in Parkinson's disease.

We assessed the use of coping strategies in Parkinson's disease patients with visual hallucinations, using a semi-structured questionnaire. We found that 36 of our 46 Parkinson's disease subjects with hallucinations (78%) used coping strategies: cognitive techniques in 69%; interactive techniques in 62%; and visual techniques in 33%.

Adaptation, Psychological↗
PubMed2003

Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders.

As there are no biological markers for the antemortem diagnosis of degenerative parkinsonian disorders, diagnosis currently relies upon the presence and progression of clinical features and confirmation depends on neuropathology. Clinicopathologic studies have shown significant false-positive and false-negative rates for diagnosing these disorders, and misdiagnosis is especially common during the early stages of these diseases. It is important to establish a set of widely accepted diagnostic criteria for these disorders that may be applied and reproduced in a blinded fashion. This review summarizes the findings of the SIC Task Force for the study of diagnostic criteria for parkinsonian disorders in the areas of Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. In each of these areas, diagnosis continues to rest on clinical findings and the judicious use of ancillary studies.

Biomarkers↗
PubMed2003

Impact of placebo assignment in clinical trials of Parkinson's disease.

Informed consent procedures in placebo-controlled trials are developed to ensure that subjects entering studies clearly understand the possibility of placebo assignment. The extent of patient understanding and the impact of learning that they were assigned placebo treatment have not been extensively studied. By using a standardized questionnaire, we interviewed 50 consecutive placebo-treated patients from 14 placebo-controlled clinical trials of Parkinson's disease (PD) after completion of their involvement. All patients interviewed understood that their study contained a placebo arm. All had hoped to receive the study drug rather than placebo, and more than half the subjects believed they had improved clinically during their placebo exposure. Positive impressions of enrollment in placebo-controlled trials were more frequent than negative, included helping to advance science (86%); liking the experience, education, and attention associated with the clinical trial (90%); and participating in research for the benefit of other patients as well as for themselves (80%). If another placebo-controlled trial was offered, 88% expressed that they would possibly, likely, or definitely be interested in enrollment. PD patients clearly understand the concept of placebo-controlled trials they complete them, but they are inaccurate in assessing whether they received placebo treatment. Although most wish they received the active compound being tested, the overall view of participation in placebo-controlled trials is viewed very positively by PD patients.

Aged↗
PubMed2003

Standardized training tools for the UPDRS activities of daily living scale: newly available teaching program.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the most widely used scale for evaluation of clinical impairment in PD. Whereas the motor section has been studied intensively for clinimetric properties and has an associated training tape, the Activities of Daily Living (ADL) section has been studied less rigorously. In preparation for a multicenter study that planned to use the UPDRS ADL score as an outcome, the authors reviewed the UPDRS ADL scale and designed a teaching program to provide a uniform technique for data acquisition without changing any wording of the primary scale. The teaching program is composed of four components: overall guidelines, clarifying points, recommended strategies, and a teaching videotape. The videotape shows examples of interviewers assessing each ADL item with patients of different disability levels and provides a complete ADL assessment of a single patient. Systematic training and utilization of this teaching program offer the potential for more uniformity in results of ADL assessments conducted in clinical practice and multicenter, international studies of PD. The written materials and videotape belong to the Movement Disorder Society and are available by contacting the MDS central office.

Activities of Daily Living↗
PubMed2003

Wheeled and standard walkers in Parkinson's disease patients with gait freezing.

OBJECTIVES: Compare the efficacy of two walking assistance devices (wheeled walker and standard walker) to unassisted walking for patients with PD and gait freezing. BACKGROUND: Although numerous walking devices are used clinically, their relative effects on freezing and walking speed have never been systematically tested. METHODS: Nineteen PD patients (14 non-demented) walked under three conditions in randomized order: unassisted walking, standard walker, and wheeled walker. Patients walked up to three times in each condition through a standard course that included rising from a chair, walking through a doorway, straightway walking, pivoting, and return. Total walking time, freezing time and number of freezes were compared for the three conditions using mixed models (walking time) and Friedman's test (freezing). The wheeled walker was further studied by comparing the effect of an attached laser that projected a bar of light on the floor as a visual walking cue. RESULTS: Use of either type of device significantly slowed walking compared to unassisted walking. Neither walker reduced any index of freezing, nor the laser attachment offered any advantage to the wheeled walker. The standard walker increased freezing, and the wheeled walker had no effect on freezing. Among the non-demented subjects (n=14), the same patterns occurred, although the walking speed was less impaired by the wheeled walker than the standard walker in this group. CONCLUSIONS: Though walkers may stabilize patients and increase confidence, PD patients walk more slowly when using them, without reducing freezing. Because the wheeled walker was intermediate for walking time and does not aggravate freezing, if walkers are used for these subjects, this type of walker should be favored.

Aged↗
PubMed2003

Pierre Marie: gifted intellect, poor timing and unchecked emotionality.

Pierre Marie was a prominent member of the French neurological world of the early twentieth century. Having been trained by the celebrated physician, J-M Charcot, Marie remained influenced by his teacher throughout his career. Because of this influence, his career can be logically divided into three phases: first, the early years under the direct mentorship of Charcot (1878-1893); secondly, the aftermath of Charcot's death when Marie left his teacher's institution, the Salpêtrière hospital and established himself at the Bicêtre hospital in southern Paris (1893-1918); and finally, Marie's return to the Salpêtrière to assume the original Charcot chaired professorship, albeit as an aged man (1918-1925). This essay examines Marie's career with an emphasis on documentation of the combined attributes of a gifted intellect as well as a heated emotionality. In the context of his time, these elements prompted Marie to enter into controversies and medico-political battles that advanced neurological knowledge, but likely disadvantaged him in his career successes.

Charcot-Marie-Tooth Disease↗
PubMed2002

The election of Sarah McNutt as the first woman member of the American Neurological Association.

The authors investigated the early women physicians of the New York Infirmary for Women and Children and their role in shaping the career and accomplishments of their student and later colleague, Dr. Sarah J. McNutt. These influences eventually led McNutt to be inducted into the American Neurologic Association (ANA). McNutt was educated at the New York Infirmary for Women and Children by early women physicians including Drs. Elizabeth and Emily Blackwell and Mary Putnam Jacobi. McNutt worked to improve the educational opportunities for practicing physicians and nurses by developing postgraduate lectures and organizations. With her early colleagues she developed the New York Infirmary for Women and Children into a reputable hospital and woman's medical college. One of the consultants to the New York Infirmary for Women and Children was Royal W. Amidon, secretary of the ANA in 1883. McNutt's close association with the Clinical Society of the New York Post Graduate Medical School and Hospital brought her into direct contact with other prominent ANA members including C.L. Dana and W.A. Hammond. In 1884, McNutt was nominated by Amidon and Hammond as the first woman member to the ANA and was elected. Her ANA thesis was Double Infantile Spastic Hemiplegia. McNutt was elected into the ANA at a time when women physicians were first being recognized and included into mainstream medicine. Her historic election acknowledged her accomplishments and highlighted the proactive role of the early ANA in forging new medical policies in the United States.

History, 19th Century↗
PubMed2002

Age at onset in two common neurodegenerative diseases is genetically controlled.

To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%--60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases.

Age of Onset↗
PubMed2002

Progressive worsening of spatial and chromatic processing deficits in Parkinson disease.

CONTEXT: Impairments of color discrimination (CD) and contrast sensitivity are established signs of Parkinson disease (PD), but their temporal evolution has not been studied. OBJECTIVE: To determine whether there is progressive, longitudinal deterioration of color discrimination (CD) and contrast sensitivity (CS) in PD. DESIGN: A prospective study. SETTING: Tertiary care center-based sample of PD patients without dementia with normal visual acuity (Snellen fraction >0.6 in the best eye). MAIN OUTCOME MEASURES: With a mean +/- SD interval of 19.8 +/- 2.8 months, the following tests were applied twice in 28 patients: the Lanthony D15 test and the Farnsworth Munsell 100 Hue test as tests of CD and the monocular and binocular Pelli-Robson test and the binocular Vistech tables as tests of CS. RESULTS: There was deterioration of both CD (Farnsworth Munsell 100 hue test: P =.002) and CS (binocular Vistech test at a spatial frequency of 6 cycles per degree, P<.001). Both deficits correlated with age, and the chromatic deficit additionally correlated with higher impairment of motor function (Unified Parkinson's Disease Rating Scale motor section, P =.04) and activities of daily life (Unified Parkinson's Disease Rating Scale activities of daily living section, P =.006). Patients with the highest pathologic psychiatric rating score (Brief Psychiatric Rating Scale) performed worse on both CS (P =.02) and CD (P =.01) at the second examination. CONCLUSIONS: Impairments of CD and CS in PD are progressive over time. Visual deficits may influence overall motor function and lead to enhanced motor impairment.

Aged↗
PubMed2002

Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease.

The Unified Parkinson's Disease Rating Scale (UPDRS) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living (ADL). Using a stringent definition of placebo effect, we examined the frequency, temporal development, and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson's disease (DATATOP). One hundred ninety-nine subjects received placebo treatment in the randomized, multicenter, placebo-controlled DATATOP study. We compared the baseline UPDRS motor section scores with follow-up scores at 4, 13, and 26 weeks. Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by two or more points. Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria. The group prevalence of response was steady (7% to 10%) at any one visit without a marked predominance of an early study effect. Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement. ADL scores were low throughout the study, and ADL improvements did not identify the subjects with objectively defined placebo-associated improvement. Prominent improvements in investigator-derived objective measures of Parkinson's disease motor impairment occur during clinical trials, including one that was not aimed at showing improved short-term efficacy. Although the notion of placebo effect often implies patient-based perceptions, we found subjective changes to be infrequent in placebo-treated patients, suggesting that either: (1) the placebo effect was rater-driven; (2) the ADL questionnaire is insensitive to transient but objectively demonstrable motor changes; or (3) that the objective changes, albeit major, are within the realm of natural variation in the UPDRS motor scale from visit to visit.

Activities of Daily Living↗
PubMed2002

History of the extensor plantar response: Babinski and Chaddock signs.

The testing of reflexes involving the lower extremities is a pivotal part of the modern neurological examination. The normal response to noxious stimulation of the foot is plantar flexion of the toes, causing them to curl downward toward the undersurface of the foot. In 1896, Joseph Babinski described an extensor toe response that he claimed was a consistent finding among patients with pyramidal tract lesions of the cortex, subcortex, brain stem, or spinal cord. He considered it a distinct sign of organic disease and found it to be absent in cases of hysterical weakness. Charles Gilbert Chaddock admired the work of Babinski and described a modification of the Babinski technique, demonstrating that stimulation of the lateral surface of the foot could induce the same type of toe extension in patients with pyramidal tract lesions. The two reflexes are complementary, and each can occur without the other, although both are usually present in cases of pyramidal tract impairment. Although these two reflexes are the most commonly described pathological reflexes indicative of pyramidal tract disruption, the names of other celebrated neurologists are also linked to the study of extensor toe signs, each having identified a variant of the Babinski sign.

History, 19th Century↗