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Objective: To establish phenotype-genotype correlations in early-onset Parkinson disease (EOPD), we performed neurologic, neuropsychological, and psychiatric evaluations in a series of patients with and without parkin mutations., Background: Parkin (PARK2) gene mutations are the major cause of autosomal recessive parkinsonism. The usual clinical features are early-onset typical PD with a slow clinical course, an excellent response to low doses of levodopa, frequent treatment-induced dyskinesias, and the absence of dementia., Methods: A total of 44 patients with EOPD (21 with and 23 without parkin mutations) and 9 unaffected single heterozygous carriers of parkin mutations underwent extensive clinical, neuropsychological, and psychiatric examinations., Results: The neurologic, neuropsychological, and psychiatric features were similar in all patients, except for significantly lower daily doses of dopaminergic treatment and greater delay in the development of levodopa-related fluctuations (p < 0.05) in parkin mutation carriers compared to noncarriers. There was no major difference between the two groups in terms of general cognitive efficiency. Psychiatric manifestations (depression) were more frequent in patients than in healthy single heterozygous parkin carriers but did not differ between the two groups of patients., Conclusion: Carriers of parkin mutations are clinically indistinguishable from other patients with young-onset Parkinson disease (PD) on an individual basis. Severe generalized loss of dopaminergic neurons in the substantia nigra pars compacta in these patients is associated with an excellent response to low doses of dopa-equivalent and delayed fluctuations, but cognitive impairment and special behavioral or psychiatric symptoms were not more severe than in other patients with early-onset PD.

Background: Stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD) and is currently performed after a mean disease duration of 14 years, when severe motor complications have resulted in marked loss of quality of life. We examined whether surgery at an early stage would maintain quality of life as well as improve motor function., Methods: Twenty patients with PD of short duration (time elapsed since first symptom +/- SD: 6.8 +/- 1.0 years) with mild to moderate motor signs (Unified Parkinson's Disease Rating Scale III "off" medication: 29 +/- 12) who responded well to levodopa treatment were included in pairs, matched for age, duration and severity of disease, and impairment in socioprofessional functioning. Patients were prospectively randomized to undergo bilateral subthalamic nucleus stimulation (n = 10) or receive optimized medical treatment (n = 10). Parkinsonian motor scores, quality of life, cognition, and psychiatric morbidity were assessed at inclusion and at 6, 12, and 18 months after randomization., Results: Quality of life was improved by 24% in surgical and 0% in nonsurgical patients (p < 0.05). After 18 months, the severity of parkinsonian motor signs "off" medication, levodopa-induced motor complications, and daily levodopa dose were reduced by 69%, 83%, and 57% in operated patients and increased by 29%, 15%, and 12% in the group with medical treatment only (p < 0.001). Adverse events were mild or transient, and overall psychiatric morbidity and anxiety improved in the surgical group., Conclusions: Subthalamic nucleus stimulation should be considered a therapeutic option early in the course of Parkinson disease.

Background: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson disease (PD). The clinical and preoperative predictive factors of the best postoperative outcome have been identified. Radiologic predictive factors were investigated., Methods: Forty patients with PD underwent surgery for bilateral STN stimulation. MRI was performed in stereotactic conditions before surgery. Brain parenchyma, caudate nucleus, putamen, pallidum, and red nucleus volumes and the surface of the mesencephalon were measured and normalized as percentages of the intracranial volume. Clinical evaluation was performed 1 month before and 6 months after surgery., Results: The normalized brain parenchyma volume was lower in patients who were older and had a longer disease duration or a lower frontal score and was not predictive of the postoperative outcome. The residual scores for activities of daily living and parkinsonian motor disability were higher in patients with a smaller normalized mesencephalon. The normalized caudate nucleus volume was predictive of the pre- and postoperative levodopa-equivalent dosage., Conclusions: Brain atrophy is not an exclusion criterion for neurosurgery, indicating that patients' neurologic, psychiatric, and neuropsychological characteristics are the best predictive factors for neurosurgery. The fact that a smaller normalized mesencephalon surface was associated with a lower beneficial effect of the subthalamic nucleus stimulation on the parkinsonian motor disability suggests that the normalized mesencephalon surface is a predictive factor of the postoperative outcome.