The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) and the outcome of lumboperitoneal shunt treatment remains to be systematically explored. Here, we aim to evaluate whether the severity of dopaminergic degeneration and white matter small vessel disease could be predictors of outcome for iNPH patients subjected to lumboperitoneal shunt treatment. This is a single center retrospective study with 39 patients with probable iNPH undergoing programmable surgical lumboperitoneal shunt from June 2016 to March 2018 at Hualien Tzu Chi Hospital. In all patients, dopaminergic degeneration was determined with 99mTc- TRODAT-1 SPECT scan, while white matter small vessel disease (Fazekas scale) was assessed with Brain MRI. The iNPH grading scale (iNPHGS) score and Karnofsky Performance Score (KPS) pre- and post-operation (6-month follow-up) were available for all patients. Linear regression was used to correlate the severities of dopaminergic degeneration and small vessel disease with lumboperitoneal shunt treatment outcomes. Their iNPHGS score improved significantly after surgery (pre-operatively, 7.8 ± 2.6; post-operatively, 5.7 ± 2.6 (26.9% improvement) (p < 0.05)). Moreover, the KPS was also improved significantly after surgery, by a mean of 24.6% from the baseline score (p < 0.05). A significant correlation was observed between the severity of dopaminergic degeneration and a poorer improvement of iNPHGS score (p = 0.03). However, improvement of the iNPHGS score was not correlated with white matter small vessel disease. Dopaminergic degeneration comorbidity neutralized the degree of improvement after surgery. Although white matter small vessel disease was correlated with iNPH incidence, it may not be a prognostic factor for shunt operation. These findings have implications for the use of dopaminergic imaging, as they might help predict the surgical outcome of patients with iNPH, while vascular mechanisms seem to be involved in iNPH pathophysiology.

Idiopathic normal pressure hydrocephalus (iNPH), albeit characterized by gait impairment, cognitive decline, and urinary incontinence, in clinical diagnosis is poorly defined and is usually coexistent with other neurodegenerative diseases. Surgical operation with shunt implantation is the primary treatment but leads to variable outcomes. Recent studies demonstrated that the pathophysiology of iNPH may include both preceding cerebrovascular events and concomitant Alzheimer's dementia or dopaminergic degenerative neuropathology in patients’ brain. These factors not only help differentiate iNPH from its mimics but also associated with the extent of symptomatic improvement after surgery. In this review, we examined these mechanisms underlying the development of iNPH and the beneficial effects of shunt surgery. Furthermore, the increasing identification and importance of biomarkers from cerebrospinal fluid and neural imaging could also predict the responsiveness of treatment. Finally, these progresses suggest that combination therapy would be necessary for iNPH treatment in the future.

A BSTRACT Objectives: Normal-pressure hydrocephalus is a clinical syndrome consisting of dilated cerebral ventricles with the clinical triad of gait disturbance, cognitive impairment and/or urinary dysfunction. Lumbar-peritoneal (LP) shunt could improve idiopathic normal pressure hydrocephalus (iNPH) while its effectiveness on secondary NPH (sNPH) is elusive. We compared the clinical results of the patients who received LP shunt surgery between iNPH and sNPH. Materials and Methods: We retrospectively analyzed the patients who received LP shunt surgery in a single center from January 1, 2017, to June 30, 2017. Patients selected for LP shunt placement had at least two of three cardinal symptoms of iNPH. The symptoms should persist for more than 3 months with compatible brain magnetic resonance imaging findings. All patients were followed up with iNPH grading scale (iNPHGS) and Modified Rankin Scale (MRS) for evaluation. Results: Thirty-three patients (23 male and 10 female patients) with mean age 76-year-old completed follow-up in this study, and 17 patients received lumbar drainage tests and intracranial pressure measurements. Both iNPH ( n = 22) and sNPH ( n = 11) groups did not have major complications such as infection, nerve root injury, or shunt failure. Both groups have significant improvement in iNPHGS and MRS. Interestingly, we found the correlation between both opening intracranial pressure and pressure gradient difference to the improvement percentage from LP shunt. Conclusion: The safety and effectiveness for sNPH patients who received LP shunt placement are equivalent to the iNPH patients. Lumbar drainage test provides prerequisite outcome prediction and should be considered to identify NPH patients planned to receive LP shunt.