Massimiliano Todisco1, Roberta Zangaglia1, Brigida Minafra1, Patrizia Pisano1, Giuseppe Trifirò1, Irene Bossert1, Nicoló Gabriele Pozzi1, Joachim Brumberg1, Roberto Ceravolo1, Ioannis Ugo Isaias1, Alfonso Fasano1, Claudio Pacchetti2. 1. From the Parkinson's Disease and Movement Disorders Unit (M.T., R.Z., B.M., N.G.P., C.P.), IRCCS Mondino Foundation; Department of Brain and Behavioral Sciences (M.T.), University of Pavia; Neurosurgery Unit (P.P.), IRCCS San Matteo Foundation; Nuclear Medicine Unit (G.T., I.B.), Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy; Neurology Department (N.G.P., I.U.I.), University Hospital and Julius Maximilian University of Würzburg; Nuclear Medicine Department (J.B.), University Hospital Würzburg, Germany; Unit of Neurology, Department of Clinical and Experimental Medicine (R.C.), University of Pisa, Italy; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic (A.F.), Toronto Western Hospital, University Health Network; Division of Neurology (A.F.), University of Toronto; Krembil Brain Institute (A.F.); and Center for Advancing Neurotechnological Innovation to Application (CRANIA) (A.F.), Toronto, Canada. 2. From the Parkinson's Disease and Movement Disorders Unit (M.T., R.Z., B.M., N.G.P., C.P.), IRCCS Mondino Foundation; Department of Brain and Behavioral Sciences (M.T.), University of Pavia; Neurosurgery Unit (P.P.), IRCCS San Matteo Foundation; Nuclear Medicine Unit (G.T., I.B.), Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy; Neurology Department (N.G.P., I.U.I.), University Hospital and Julius Maximilian University of Würzburg; Nuclear Medicine Department (J.B.), University Hospital Würzburg, Germany; Unit of Neurology, Department of Clinical and Experimental Medicine (R.C.), University of Pisa, Italy; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic (A.F.), Toronto Western Hospital, University Health Network; Division of Neurology (A.F.), University of Toronto; Krembil Brain Institute (A.F.); and Center for Advancing Neurotechnological Innovation to Application (CRANIA) (A.F.), Toronto, Canada. claudio.pacchetti@mondino.it.
Abstract
OBJECTIVE: To determine changes in clinical features and striatal dopamine reuptake transporter (DAT) density after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Participants with probable iNPH were assessed at baseline by means of clinical rating scales, brain MRI, and SPECT with [123I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT). Levodopa responsiveness was also evaluated. Patients who did or did not undergo lumboperitoneal shunt were clinically followed up and repeated SPECT after 2 years. RESULTS: We enrolled 115 patients with iNPH. Of 102 patients without significant levodopa response and no signs of atypical parkinsonism, 92 underwent FP-CIT SPECT (58 also at follow-up) and 59 underwent surgery. We identified a disequilibrium subtype (phenotype 1) and a locomotor subtype (phenotype 2) of higher-level gait disorder. Gait impairment correlated with caudate DAT density in both phenotypes, whereas parkinsonian signs correlated with putamen and caudate DAT binding in patients with phenotype 2, who showed more severe symptoms and lower striatal DAT density. Gait and caudate DAT binding improved in both phenotypes after surgery (p < 0.01). Parkinsonism and putamen DAT density improved in shunted patients with phenotype 2 (p < 0.001). Conversely, gait, parkinsonian signs, and striatal DAT binding worsened in patients who declined surgery (p < 0.01). CONCLUSIONS: This prospective interventional study highlights the pathophysiologic relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and postsurgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of patients with iNPH.
OBJECTIVE: To determine changes in clinical features and striatal dopamine reuptake transporter (DAT) density after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Participants with probable iNPH were assessed at baseline by means of clinical rating scales, brain MRI, and SPECT with [123I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT). Levodopa responsiveness was also evaluated. Patients who did or did not undergo lumboperitoneal shunt were clinically followed up and repeated SPECT after 2 years. RESULTS: We enrolled 115 patients with iNPH. Of 102 patients without significant levodopa response and no signs of atypical parkinsonism, 92 underwent FP-CIT SPECT (58 also at follow-up) and 59 underwent surgery. We identified a disequilibrium subtype (phenotype 1) and a locomotor subtype (phenotype 2) of higher-level gait disorder. Gait impairment correlated with caudate DAT density in both phenotypes, whereas parkinsonian signs correlated with putamen and caudate DAT binding in patients with phenotype 2, who showed more severe symptoms and lower striatal DAT density. Gait and caudate DAT binding improved in both phenotypes after surgery (p < 0.01). Parkinsonism and putamen DAT density improved in shunted patients with phenotype 2 (p < 0.001). Conversely, gait, parkinsonian signs, and striatal DAT binding worsened in patients who declined surgery (p < 0.01). CONCLUSIONS: This prospective interventional study highlights the pathophysiologic relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and postsurgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of patients with iNPH.
Authors: Anna L Bartels; Bauke M de Jong; Nir Giladi; Joanna D Schaafsma; R Paul Maguire; Lammy Veenma; Jan Pruim; Yacov Balash; Moussa B H Youdim; Klaus L Leenders Journal: Mov Disord Date: 2006-09 Impact factor: 10.338
Authors: Nicole C Keong; Alonso Pena; Stephen J Price; Marek Czosnyka; Zofia Czosnyka; Elise E DeVito; Charlotte R Housden; Barbara J Sahakian; John D Pickard Journal: PLoS One Date: 2017-08-17 Impact factor: 3.240
Authors: Phillip A Bonney; Robert G Briggs; Kevin Wu; Wooseong Choi; Anadjeet Khahera; Brandon Ojogho; Xingfeng Shao; Zhen Zhao; Matthew Borzage; Danny J J Wang; Charles Liu; Darrin J Lee Journal: Front Aging Neurosci Date: 2022-04-28 Impact factor: 5.750