Dopaminergic agonists in the treatment of Parkinson's disease.
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Bromocriptine↗
Biomedical subjects
C G Goetz
Publications and source records attributed to C G Goetz.
[Where are the grafts in Parkinson's disease?].
Although laboratory studies started about twenty years ago, the international interest in transplants for Parkinson's disease was not aroused until the 1980's. Since the spectacular report by Madrazo et al. (1987), several groups of research-workers in various parts of the world are trying to reproduce or surpass these results. The latest studies indicate that while patients draw some benefits from adrenal medullary transplant to caudate nucleus, the operation involves inordinary risks. Moreover, the efficacy of this method is clearly less impressive now than was originally reported.
Adrenal Medulla↗
Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease.
In 19 patients with severe Parkinson's disease, we replicated the surgical procedures developed by Madrazo et al. for transplantation of the adrenal medulla to the striatum, and followed them for six months after operation. We monitored their motor function with the use of standardized scales and determined the amount and quality of "on" and "off" time (the hours of the waking day when the antiparkinsonian medications were effective and ineffective, respectively). We found significant improvement in focal areas of motor function. The mean percentage of on time during the day increased from 47.6 percent to 75.0 percent (P = 0.012); the mean percentage of on time without chorea increased from 26.6 percent to 59.2 percent (P = 0.006); the mean severity of off time decreased as assessed by both the Activities of Daily Living subscale of the Unified Parkinson's Disease Scale (P = 0.002) and the Schwab and England scale (P = 0.037). In contrast to the finding of Madrazo et al., however, the dosages of antiparkinsonian medications could not be decreased and postoperative morbidity was substantial. Despite cautious optimism, we conclude that the widespread use of this procedure outside of research centers is premature, since the improvement we found was slighter than in the previous cases.
Activities of Daily Living↗
Hypersexuality with antiparkinsonian therapy.
Thirteen parkinsonian patients drawn from two large parkinsonism clinics experienced hypersexuality as a consequence of anti-parkinsonian therapy. The cases include only those whose sexual behavior on treatment became a concern to the patient's family or a social agency. The majority of patients were men and had a relatively early onset of parkinsonian symptomatology. There was no relation between functional improvement and increased sexuality. Most patients showed some element of dose dependency between antiparkinsonian drugs and the hypersexual behavior. Prior sexual profile included from no sexual outlet to hypersexuality. Neither the prior history of psychiatric illness nor brain damage predisposed to such response on treatment, and in most patients, it was not a part of hypomania or a more diffuse psychiatric disturbance. We propose that hypersexuality on antiparkinsonian drugs is consequent to inhibition of prolactin secretion.
Adult↗
Environmental factors and Parkinson's disease: a case-control study in China.
We studied the role of environment in the development of Parkinson's disease (PD) in China, where industrialization is relatively recent and the population geographically stable. Using a case-control method, we investigated the relationship between PD and exposure to the following factors before disease onset: place of residence, source of drinking water, environmental and occupational exposure to various agricultural and industrial processes. Occupational or residential exposure to industrial chemicals, printing plants, or quarries was associated with an increased risk of developing PD. In contrast, living in villages and exposure to the common accompaniments of village life, wheat growing and pig raising, were associated with a decreased risk for PD. PD cases and controls did not differ with respect to other factors investigated. These findings are consistent with the hypothesis that environmental exposure to certain industrial chemicals may be related to the development of PD.
Adult↗
Agonist substitution in advanced Parkinson's disease.
We studied whether Parkinson's disease patients who had lost efficacy from pergolide (PERG) could benefit if transferred to bromocriptine (BCT) therapy. Using paired t-tests, we compared motor scores at baseline (when patients were still on PERG) and after 6 months of BCT therapy in 11 patients. No significant improvement occurred in any measure on BCT therapy (mean dose 33.6 mg/day), although patients remained stable. In 6 patients on whom "on/off" data were obtained, decreased "off" time and increased "on" time without chorea occurred, but these changes were not statistically significant. The side effect profile was similar with the 2 drugs.
Aged↗
Induction of parkinsonism by intraventricular bethanechol in a patient with Alzheimer's disease.
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Aged↗
Dystonic posturing in temporal lobe seizures.
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Child↗
Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa.
We compared the chronic (2-year) effect of substitution with Sinemet CR with the effect of continued administration of standard Sinemet on motor fluctuations and drug-induced side effects in Parkinson's disease (PD). Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry. After 2 years, both groups were more disabled from their PD than at baseline; the disability scores were equivalent for the 2 treatments. The Sinemet CR group had fewer fluctuations and fewer side effects. Compared with the standard Sinemet group, Sinemet CR patients had more "on" time (mean 83% versus 62%, p less than 0.001), and had a lower prevalence of disabling chorea (p less than 0.007), dystonia (p less than 0.003) and sleep disruption (p less than 0.002). Prevalence of hallucinations was equivalent for the 2 groups. These results suggest that Sinemet CR is beneficial in ameliorating and preventing the high frequency of some side effects of standard Sinemet treatment.
Antiparkinson Agents↗
An antibody in the CSF of Parkinson's disease patients disappears following adrenal medulla transplantation.
CSF from Parkinson's disease (PD) patients undergoing autologous transplantation of adrenal medulla tissue into their lateral ventricle was examined for the presence of IgG. CSF from 6 of 7 patients incubated with rat brain tissue reacted immunocytochemically to neuronal cell bodies in the substantia nigra and ventral tegmental region. This reactivity gradually disappeared in the months following transplantation. Five of 6 CSF samples from non-transplanted PD patients also produced this immunocytochemical reactivity whereas 26 non-PD samples were immunonegative. Possible implications to the transplant procedure are discussed.
Adrenal Medulla↗
The Salpêtrière in the wake of Charcot's death.
After Charcot died in 1893, the students of his immediate circle did not fare well academically in the French medical system. Fatigue and bitterness toward the authoritarian Charcot may have contributed to the change in the scientific and social ambience of the Salpêtrière of Paris in the generation after Charcot died. Clearly, however, the faculty were not invested in energetically overturning the system that Charcot had established, and their choice of Fulgence Raymond as Charcot's successor was an effective means of permitting a passive waning in the Salpêtrière's magnetic influence in world neurology.
Faculty, Medical↗
Shakespeare in Charcot's neurologic teaching.
Charcot frequently used Shakespearean references in his neurologic teaching sessions. With these citations, he emphatically stressed how objective observation and an attention to detail were essential to expert clinical diagnosis. At the same time, Charcot presented his personal credentials as a cultured man. Charcot's interest in Shakespeare permeated many aspects of his professional work, and also his private and family life.
Drama↗
Case 2, 1988. Congenital mental retardation and juvenile parkinsonism.
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Adolescent↗
Concurrent treatment with benztropine and haloperidol attenuates development of behavioral hypersensitivity but not dopamine receptor proliferation.
Groups of male rats (n = 16 each) were treated with normal saline, haloperidol (0.75 mg/kg), benztropine (1.8 mg/kg) or haloperidol and benztropine once a day for 24 days. Following a 96 hour drug free interval, subsets of these animals were assessed for apomorphine-induced (0.75 mg/kg) stereotypic behavior, sacrificed and analyzed for striatal dopamine biochemistry or sacrificed and analyzed for spiroperidol binding sites. Benztropine cotreatment attenuated the development of behavioral hypersensitivity to haloperidol but did not alter either the dopamine receptor proliferation or the striatal dopamine biochemical changes induced by haloperidol. These results suggest that behavioral hypersensitivity is not an automatic manifestation of dopamine receptor proliferation but must depend, in part, on other factors.
Animals↗
Risk factors for progression in Parkinson's disease.
Using case-control methodology, we assessed prevalence and duration of exposure to putative risk factors for rapid progression of Parkinson's disease (PD) in patients not taking levodopa or direct dopamine agonists. We identified 31 patients termed "rapidly progressive" who were stage I or II (Hoehn and Yahr) on their first visit to our center and who progressed to stage III during the study period; we pair-matched this group with 31 "slowly progressive" patients who had the same symptom duration and the same Hoehn and Yahr stage at study entry, but whose parkinsonism did not progress to stage III during the study. Only age of PD onset was associated with different rates of PD progression; older patients at PD onset progressed more rapidly than younger patients.
Age Factors↗
Hemiparkinsonism with hemiatrophy.
We studied fifteen patients with hemiparkinsonism and ipsilateral hemiatrophy (HP/HA) to better characterize the clinical features of this syndrome and its rate of progression. Patients were distinguished by highly asymmetric parkinsonism with predominant signs on the side of HA, early age of onset (43.7 years versus 60.2 years in our control population of idiopathic Parkinson's disease [IPD], abnormal birth history (7/15), and dystonia occurring prior to levodopa therapy (10/15). In six patients, the mean duration of disease until the initiation of levodopa therapy was 14.2 years, as compared with 4.1 years in our control population of IPD. The slow progression of disease underscores the relatively favorable prognostic significance of HP/HA and its distinction from IPD.
Adult↗
Controlled-release carbidopa/levodopa (CR4-Sinemet) in Parkinson's disease patients with and without motor fluctuations.
Sixteen patients with advanced Parkinson's disease (PD) and motor fluctuations were evaluated throughout 12 months of open label therapy on CR4-Sinemet. Reduced dosage frequency and significant motor improvement with reduced fluctuation occurred and were maintained with CR4-Sinemet compared with baseline on Sinemet. In a double-blind protocol using CR4-Sinemet in 20 stable PD patients, CR4-Sinemet was given twice daily and compared with Sinemet given four times daily. Patients remained stable without improvement or deterioration when the long-acting drug was substituted at 50% frequency. Plasma levodopa levels with CR4-Sinemet were smoother than with Sinemet. Although some patients receiving CR4-Sinemet found they functioned more slowly in the morning, the easier dosing schedule and improved amount of "on" time in fluctuators suggest that this formulation may become increasingly useful in managing PD.
Adult↗
The adrenal medullary transplant operation for Parkinson's disease: clinical observations in five patients.
The recent report by Madrazo and coworkers on the successful treatment of Parkinson's disease using adrenal medullary tissue transplanted to the caudate nucleus has aroused international interest in the procedure. The present article reports our initial experiences with the operation in five patients and discusses the postoperative effects of the procedure, the protocol used to monitor motor performance, and the need for cooperation with the two registries that have been created to follow morbidity, mortality, and efficacy. We intend to alert the neurosurgeon to important side effects, but not to assess the long term efficacy of the procedure. Postoperatively, a number of transient effects were seen in our patients, the most striking being somnolence, delusions, and lack of significant pain in spite of a large abdominal incision. The only complications have been respiratory. After the early postoperative period, gradual improvement of on-off times and Schwab-England disability scores was seen over 20 weeks. Long term cooperative studies are needed to demonstrate the efficacy of this procedure. neurosurgeons doing transplant operations are urged to join the registries so that uniform information can be collected.
Adrenal Medulla↗