Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

Humans Dyskinesias / etiology Globus Pallidus / surgery Parkinson Disease / complications Treatment Outcome High-Intensity Focused Ultrasound Ablation

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
23 02 2023
Historique:
entrez: 22 2 2023
pubmed: 23 2 2023
medline: 25 2 2023
Statut: ppublish

Résumé

Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies. We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months. Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

Sections du résumé

BACKGROUND
Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies.
METHODS
We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months.
RESULTS
Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.
CONCLUSIONS
Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

Identifiants

DOI: 10.1056/NEJMoa2202721 PMID: 36812432
pubmed: 36812432
doi: 10.1056/NEJMoa2202721
doi:

Banques de données

ClinicalTrials.gov
['NCT03319485']

Types de publication

Randomized Controlled Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

683-693

Commentaires et corrections

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Informations de copyright

Copyright © 2023 Massachusetts Medical Society.

Auteurs

Vibhor Krishna (V)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).
ORCID: 0000-0002-4141-4192

Paul S Fishman (PS)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Howard M Eisenberg (HM)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Michael Kaplitt (M)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Gordon Baltuch (G)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Jin Woo Chang (JW)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Wei-Chieh Chang (WC)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).
ORCID: 0000-0001-6089-2010

Raul Martinez Fernandez (R)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Marta Del Alamo (M)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Casey H Halpern (CH)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Pejman Ghanouni (P)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Roberto Eleopra (R)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Rees Cosgrove (R)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Jorge Guridi (J)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Ryder Gwinn (R)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Pravin Khemani (P)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Andres M Lozano (AM)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Nathan McDannold (N)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Alfonso Fasano (A)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).
ORCID: 0000-0001-5346-0180

Marius Constantinescu (M)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Ilana Schlesinger (I)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

Arif Dalvi (A)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

W Jeff Elias (WJ)

From the University of North Carolina, Chapel Hill (V.K.); University of Maryland, Baltimore (P.S.F., H.M.E.); Cornell University (M.K.) and Columbia University (G.B.) - both in New York; Yonsei University, Seoul (J.W.C.); Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (W.-C.C.); Centro Integral de Neurociencias Abarca Campal-HM Puerta Del Sur, Madrid (R.M.F., M.A.), and Clínica Universidad de Navarra, Pamplona (J.G.) - both in Spain; University of Pennsylvania, Philadelphia (C.H.H.); Stanford University, Stanford, CA (P.G.); Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy (R.E.); Harvard University, Boston (R.C., N.M.); Swedish Hospital, Seattle (R.G., P.K.); University of Toronto, Toronto (A.M.L., A.F.); Rambam Health Care Campus, Haifa, Israel (M.C., I.S.); Palm Beach Neuroscience Institute, Boynton Beach, FL (A.D.); and University of Virginia, Charlottesville (W.J.E.).

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