Objective: To determine the prevalence of α-synuclein (AS) aggregates in abdominopelvic autonomic plexuses in the general population and to evaluate the relationship between this finding and the subsequent development of neurologic dysfunction. Methods: First, surgical specimens from 100 patients (ages 44 to 84) undergoing a wide resection of an abdominopelvic organ were examined by anti-AS immunostaining. Second, 16 patients (6 AS+ and 10 randomly selected AS−) participated in yearly double-blinded neurologic assessments. Results: AS aggregates were found in autonomic plexuses in 9% of the whole sample (95% CI 3.4 to 14.6%) but were more common in vesicoprostatic (26%) than in digestive tract (4%) specimens. At 16 months after the biopsy, no prevalent cases of Parkinson disease, dementia, or autonomic failure were diagnosed among participants. One AS+ patient had previously been diagnosed with REM sleep behavior disorder. Seven of 10 control subjects but none of the 6 AS+ patients had a diagnosis of hypertension (p = 0.01). During phase IV of Valsalva maneuver, AS+ group exhibited a longer blood pressure recovery time (p = 0.03), with one patient showing absence of blood pressure overshoot. Cardiac [¹²³I]metaiodobenzylguanidine uptake was reduced in the AS+ group (p = 0.03). Striatal [¹²³I]ioflupane uptake was abnormally low in only one AS+ patient. At 30 months after the biopsy, lower cardiac and striatal uptake values tended to correlate with higher Unified Parkinson9s Disease Rating Scale III scores (p = 0.07). Conclusion: The common presence of α-synuclein aggregates in peripheral autonomic neurons may represent an early presymptomatic phase in the development of Lewy body disorders.

Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD). Objective: We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD. Methods: Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson’s Disease Rating Scale III score in the off-medication state. Seven patients had ¹⁸F-dopa positron emission tomography scans before and 1 year after transplantation. Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off-period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non-significant 5% increase in mean putaminal ¹⁸F-dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal ¹⁸F-dopa uptake (r = −0.829; p = 0.042). Conclusions: CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.

OBJECTIVE. In this study, we assessed the feasibility of autotransplantation of carotid body (CB) cell aggregates into the striatum for the treatment of

Background: Dystonia is a complex clinical syndrome originated by a wide range of aetiologies. The diagnosis of dystonia is made after the evaluation of aetiological, phenomenological and genetic factors.1 Medications, except in patients with dopa-responsive dystonia, are of limited efficacy. Botulinum toxin injections are not applicable to patients with generalised dystonia, since many muscular groups contribute to disability.2 Clinical studies in children and adults with primary generalised dystonia (PGD) have reported beneficial effects of bilateral GPi deep brain stimulation (DBS) in both motor symptoms and disability produced by dystonia3 4 5 as well as a favourable impact of DBS in the health-related quality of life (HRQoL).6 Some clinical aspects of GPi stimulation in primary dystonia still remain controversial such as the influence of disease duration or age at onset in determining the postoperative clinical outcome. Results: The authors report the results of a multicentric study designed to assess the tolerability and clinical effects of bilateral pallidal DBS on motor impairment, functional disability, quality of life, pain and mood in patients with medically refractory primary generalised or segmental dystonia.