Clinical Outcome and Striatal Dopaminergic Function After Shunt Surgery in Patients With Idiopathic Normal Pressure Hydrocephalus

Massimiliano Todisco, Roberta Zangaglia, Brigida Minafra, Patrizia Pisano, Giuseppe Trifirò, Irene Bossert, Nicoló Gabriele Pozzi, Joachim Brumberg, Roberto Ceravolo, Ioannis Ugo Isaias, Alfonso Fasano, Claudio Pacchetti

Research output: Contribution to journalArticlepeer-review

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: Subjects 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 iNPH patients. Of 102 subjects without significant levodopa response and no signs of atypical parkinsonism, 92 performed 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 subjects who declined surgery (p < 0.01).

CONCLUSIONS: This prospective interventional study highlights the pathophysiological relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and post-surgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of iNPH patients.

Original languageEnglish
JournalNeurology
DOIs
Publication statusE-pub ahead of print - Apr 23 2021

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