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This study is based on long-term follow-up of participants in a randomized double-blind sham surgery-controlled trial (1995–1999) designed to determine the effectiveness of implantation of human embryonic mesencephalic tissue containing dopamine neuron precursors into the brains of patients with advanced Parkinson’s disease (PD). We investigated differences between long-term survivors and nonsurvivors at baseline in order to contribute to information regarding optimal patient selection for upcoming stem cell trials.
Forty participants were randomly assigned to receive either neural implantation or sham surgery. Thirty-four patients who ultimately received the implant were followed periodically with the most recent assessment occurring in 2015–2016. Demographic information, neurological measures, positron emission tomography (PET) imaging, neuropsychological assessments, and a personality assessment were included in the current analyses. T-tests were used to compare survivors and nonsurvivors. Logistic regression analyses examined predictors of survivorship.
Five of six survivors were female. They were younger than nonsurvivors (p = .03) and more neuropsychologically “intact” across a broad range of cognitive areas (significance levels ranged from <.001 to .045). There were no differences between survivors and nonsurvivors off medications at baseline on neurological or PET assessments. Survivors reported more “Openness to Experience” (p = .004) than nonsurvivors. Using empirically derived predictor variables, results of logistic regression analyses indicated that Animal Naming (cognitive task) and Openness to Experience (personality variable) were the strongest predictors of survivorship.
Variables to consider when selecting participants for future cell-based therapies include being “intact” neuropsychologically, level of Openness to Experience, younger age, and inclusion of women.
A number of pharmacologic agents have been found to be effective for the dystonias. Anticholinergic drugs have been shown to be the most effective in terms of percentage of subjects who receive moderate to marked benefit. About 50% of children and 40% of adults obtain such improvement. Peripheral adverse effects are usually overcome by pyridostigmine. It may be necessary to utilize pilocarpine eyedrops for blurred vision. Central adverse effects, such as forgetfulness, can be reduced only by a reduction in dosage of the anticholinergic. In comparing trihexyphenidyl and ethopropazine, we found that children tend to have better tolerance of the former and adults tend to have better tolerance of the latter. The antidopaminergics are the group of drugs that were found to be the next most effective agents in terms of percentage of patients who respond. However, these drugs, particularly the dopamine receptor blockers, have the capacity to induce tardive dyskinesia and tardive dystonia. Tardive syndromes are difficult to treat and can persist indefinitely. Other agents that have shown usefulness in controlling dystonia are levodopa, baclofen, carbamazepine, and the benzodiazepines, either alone or in combination with each other and with the anticholinergics. Stereotactic thalamotomy is particularly useful in contralateral hemidystonia. The risk of adverse effects is less than with bilateral thalamotomy, which may need to be employed when generalized dystonia is severely disabling and not responsive to pharmacotherapy.
We define the meaning of early and late treatments and present arguments opposed to early treatment with levodopa. These are based on the development of complications with long-term Sinemet which include clinical fluctuations, loss of efficacy, and painful dystonic cramps. By delaying the onset of levodopa therapy until the symptoms require this most potent of antiparkinsonian agents, we can delay the onset of these disabling problems. Also, using as low a dosage as possible should reduce the risk of any long-term complication related to accumulative dose.
We also present the serial evaluations of 26 patients followed for as long as 7.5 years before levodopa therapy was initiated. Three scoring scales on these patients are compared. Arguments are presented which suggest that the Columbia University and the ADL scales are superior to the UCLA scale, and more closely approximate the curve of the progressive clinical disability of the disease as assessed by global evaluation. We conclude that the ultimate answer to any clinical debate must come from well-designed, controlled studies to assess the differences between two treatment modalities.
The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)
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