Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus

Abstract

Background Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. Objectives To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. Methods We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123I]‐N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane and single‐photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l‐dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale. All patients completed a 2‐year follow‐up. Results A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. Conclusions Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society

Effect of Cerebrospinal Fluid Area Mask Correction on 123I-FP-CIT SPECT Images in Idiopathic Normal Pressure Hydrocephalus

“…This previous study has included a small number of iNPH in the group without parkinsonism. Recent studies have revealed that DAT availability decreases from 30.8-62.0% in patients with iNPH [12,13,14]. In other words, the results of discrimination in their study may vary depending on the proportion of iNPH with and without the pathophysiology of DAT reduction, if a large number of iNPH subjects were included.…”

“…These ndings suggest that CSF area mask correction might affect the visual and quantitative assessment of iNPH. The pathophysiology of DAT reduction, which was observed in approximately 30-60% of iNPH, has not been clari ed [12,13,14]. Therefore, future studies of DAT availability in iNPH require more accurate visual and quantitative analyses.…”

“…To date, the DAT imaging ndings of iNPH have been reported to be normal because iNPH does not involve the degeneration of the nigrostriatal neurons [10,11]. However, it has recently been reported that DAT on DAT imaging was reduced in 30.8-62.0% of patients with iNPH [12,13,14]. Furthermore, different from PD showing DAT reduction in the putamen predominantly, iNPH may be characterized by DAT reduction in the caudate as much as the putamen [15].…”

Differentiating comorbidities and predicting prognosis in idiopathic normal pressure hydrocephalus using cerebrospinal fluid biomarkers

“…However, by definition, iNPH shows no abnormalities on these tests. Nonetheless, as is the case with AD, comorbidity of PD and iNPH is not uncommon ( 58 ), and even the confirmation of DESH findings cannot rule out comorbid PD ( 59 ). If comorbidity is suspected, carefully determining the extent of iNPH involvement in the present symptoms using the response to a tap test and observing the reaction to dopamine replacement therapy for PD (L-dopa test) can aid diagnosis ( 60 ).…”

Symptomatische Behandlungsoptionen chronischer, neurologischer Gangstörungen

“…Auch bei einigen Patienten mit NPH findet sich ein reduzierter striataler Dopaminstoffwechsel. Ein unterstützender dopaminerger Therapieversuch erweist sich in diesem Krankheitsbild trotzdem nur in sehr seltenen Fällen als hilfreich, zumal hier durch die Shuntoperation und in Form von antidementiven Medikamenten alternative Optionen bestehen [13].…”