Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus

https://doi.org/10.1016/j.jns.2015.06.029Get rights and content

Highlights

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    Idiopathic normal-pressure hydrocephalus (iNPH) occasionally shows Alzheimer pathology.

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    Amyloid in the brain of iNPH was evaluated using positron emission tomography.

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    Clinical symptoms were assessed before and after shunt surgery.

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    Lower amyloid levels were associated with greater cognitive improvement after surgery.

Abstract

Objectives

In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimer's pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimer's disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery.

Materials & methods

Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, 11C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery.

Results

Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH.

Conclusions

The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery.

Introduction

Idiopathic normal-pressure hydrocephalus (iNPH) manifests as a triad of dementia, gait disturbance, and urinary incontinence, with ventriculomegaly and normal cerebrospinal fluid (CSF) pressure in addition to no preceding events, such as meningitis or subarachnoid hemorrhage. This syndrome is typically treated with CSF shunt surgery, with clinical improvement being documented following shunt placement in 47–90% of cases [1], [2], [3], [4].

In the clinical diagnosis of iNPH, differential diagnosis from AD can be problematic, as both diseases cause dementia and ventriculomegaly. Furthermore, some iNPH cases may present comorbidity of AD, based on symptomatic or radiological features of the disease. Amyloid pathology has been found in 22.2–67.6% of cortical specimens of iNPH patients obtained during intracranial pressure monitoring or shunt surgery [5], [6]. Moderate to severe AD pathology is associated with worse baseline cognitive performance and diminished postoperative improvement of symptoms [6]. Thus, knowledge about the preoperative comorbidity of AD may be useful for clinical decision-making.

Recently, in vivo imaging of AD pathology in the brain has become possible using positron emission tomography (PET). 11C-BF227 is a radiopharmaceutical used for amyloid PET imaging [7]. A previous study using 11C-BF227-PET demonstrated that this tracer is taken up in the cerebral cortices of patients with AD but not in those of normal subjects because of the dense amyloid deposition in patients with AD [8].

In this study, we evaluated amyloid deposition in the brains of iNPH patients before shunt surgery and investigated the association between amyloid deposition in the brain and clinical improvement following shunt surgery in patients with iNPH.

Section snippets

Subjects

Patients who were diagnosed with iNPH and indicated for shunt surgery were enrolled in this prospective study at Tohoku University Hospital, Sendai, Japan between November 2010 and July 2013. Patients were diagnosed with iNPH by board-certified neurologists based on the diagnostic criteria of the Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus from the Japanese Society of Normal Pressure Hydrocephalus [9]. The diagnostic criteria are (1) symptoms developing when the

Results

Eleven patients were enrolled in the present study. Among them, 1 patient was subsequently excluded from the analysis because the patient experienced a cerebral hemorrhage in the perioperative period. The demographic data of the subjects are shown in Table 1. The mean age of the iNPH group was significantly higher than that of the healthy control and AD groups. There was no sex difference between the groups. The mean MMSE scores of both the iNPH and AD groups were significantly lower than those

Discussion

In this study, half of the patients with iNPH had neocortical SUVRs as high as those of patients with AD, whereas the other half of the patients with iNPH had SUVRs as low as those of healthy control subjects. This result suggests that the amyloid burden in the brains of patients with iNPH varies widely. However, this result cannot be interpreted with certainty because the correlation between 11C-BF227 uptake and amyloid deposits in the brain has not been established. Nevertheless, this

Conclusions

Although cortical amyloid deposits may be examined by cortical biopsy, amyloid PET imaging is advantageous because it is less invasive and evaluates all of the cerebral cortex during the diagnostic phase. Through preoperative examinations using 11C-BF227-PET imaging, our study demonstrated that the amount of amyloid deposits in the brain is associated with the cognitive outcome of shunt surgery. Further large-scale trials are required to confirm the validity of this imaging application.

Conflict of interest

The authors declare no financial or other conflict of interest.

Acknowledgments

The authors thank Yoichi Ishikawa (Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University) for the production of 11C-BF227 and Shoichi Watanuki (Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University) for the acquisition of PET data. This study was supported by a Japan Society for the Promotion of Science KAKENHI Grant, Number 23791388.

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