Foltynie, T. (Thomas)

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2013 - 20202

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    Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson’s disease
    (2020) Piccini, P. (Paola); Roussakis, A.A. (Andreas-Antonios); Martín-Bastida, A. (Antonio); Barker, R.A. (Roger A.); Valle-Guzman, N. (Natalie); Soreq, E. (Eyal); Daws, R.E. (Richard E.); Hampshire, A. (Adam); Paul, G. (Gesine); Lao-Kaim, N.P. (Nick P.); Foltynie, T. (Thomas); Li, W. (Weihua)
    Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson’s disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11CPE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. Results: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. Conclusions: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression.
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    Short and long term outcome of bilateral pallidal stimulation in chorea-acanthocytosis
    (Public Library of Science, 2013) Cho, J.W. (Jin Whan); Miquel, M. (Marie); Shin, H. (Hyeeun); Kefalopoulou, Z.M. (Zinovia Maria); Jarman, P. (Paul); Danek, A. (Adrian); Guridi-Legarra, J. (Jorge); Hariz, M. (Marwan); Bertram, K. (Kelly); Zrinzo, L. (Ludvic); Guehl, D. (Dominique); Lozano, A.M. (Andres M.); Bhatia, K. (Kailash); Gimenez-Roldan, S. (Santiago); Limousin, P. (Patricia); Garcia-Ruiz, P.J. (Pedro J.); Walker, R.H. (Ruth H.); Aviles-Olmos, I. (Iciar); Bader, B. (Benedikt); Moro, E. (Elena); Yokochi, F. (Fusako); Burghaus, L. (Lothar); Rodriguez-Oroz, M.C. (María Cruz); Latxague, C. (Chrystelle); Lipsman, N. (Nir); Burbaud, P. (Pierre); Shang, H. (Huifang); Cuny, E. (Emmanuel); Tison, F. (François); Foltynie, T. (Thomas); Spampinato, U. (Umberto); Ngy, D. (Dhita)
    BACKGROUND: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. METHODS: Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). RESULTS: Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥ 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. CONCLUSION: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.