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J Neurol. 2018 Sep;265(9):1989-1997. doi: 10.1007/s00415-018-8955-z. Epub 2018 Jun 26.

Beyond 35 years of Parkinson's disease: a comprehensive clinical and instrumental assessment.

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Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, 10124, Turin, Italy.
Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, 10124, Turin, Italy.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal.
Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Department of Psychology, University of Turin, Via Verdi 10, 10124, Turin, Italy.
Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Parkinson Institute, ASST "G.Pini-CTO", Via Bignami 1, Milan, 20133, Italy.



We sought to characterize the clinical, neuropsychological, electrophysiological, and neuroimaging features of Parkinson's disease (PD) after over 35 years since the onset of motor symptoms.


Five consecutively consenting PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) were recruited in a cross-sectional study of motor (Unified PD Rating Scale section-III), non-motor (Non-Motor Symptoms Scale), autonomic (Scale for Outcome in PD-Autonomic), and neuropsychological features associated with the very advanced phase of PD. In addition, patients underwent neurophysiological (autonomic tests and nerve conduction studies) and neuroimaging (brain MRI, 123I-FP-CIT SPECT, and 123I-MIBG myocardial scintigraphy) studies, as well as a genetic analysis of 34 genes and single nucleotide polymorphisms associated with PD.


There was a sustained motor response to L-dopa (range 14.4-35.6%), STN-DBS (23.3-38.4%), and L-dopa plus STN-DBS (37.8-63.0%). There were mild-to-moderate non-motor symptoms (range 19-83 on a scale of 0 to 360) and autonomic dysfunction (8-28 on a scale of 0-69). Two patients were demented, one had mild cognitive impairment, and two were cognitively preserved. Three patients had a sensory-axonal peripheral neuropathy and two a moderate-to-severe autonomic neuropathy. All cases showed a complete nigro-striatal dopaminergic denervation and a severe cardiovascular noradrenergic denervation. The brain MRI revealed only moderate frontal atrophy. The genetic tests were unremarkable.


Even after more than 35 years of disease, L-dopa  and STN-DBS remain effective on PD cardinal symptoms. Although axial, autonomic, and neuropsychological features may become key determinants of disability, some patients maintain a satisfactory quality of life, without significant motor and non-motor impairment.


Deep brain stimulation; Late stage; Parkinson’s disease

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