Journal List > Dement Neurocogn Disord > v.17(1) > 1120128

Dement Neurocogn Disord. 2018 Mar;17(1):32-36. English.
Published online Mar 26, 2018.  https://doi.org/10.12779/dnd.2018.17.1.32
© 2018 Korean Dementia Association
Hydrocephalus in a Patient with Alzheimer's Disease
Min Ju Kang,1 Young Ho Park,1 SangYun Kim,1 and SangHak Yi2
1Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea.
2Department of Neurology, Wonkwang University School of Medicine, Iksan, Korea.

Correspondence to SangHak Yi, MD. Department of Neurology, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan 54538, Korea. Email: md0626@naver.com
Received Feb 07, 2018; Revised Feb 26, 2018; Accepted Feb 26, 2018.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

Background

Normal pressure hydrocephalus (NPH) is an etiology of dementia that is reversible following cerebrospinal fluid shunt placement, however, surgical intervention not always clinically effective and the respons to shunt therapy is poorly understood. Furthermore, NPH is a source of comorbidity in diseases with neurodegenerative pathology, such as Alzheimer's disease (AD).

Case Report

A 61-year-old woman presented to the neurology clinic with progressive gait difficulties and cognitive impairment over five years. Nine years after ventriculoperitoneal (VP) shunt treatment, the patient began to experience frequent falls. There was no improvement in clinical symptoms after the alteration of valve pressure on the VP shunt. An 18F-florbetaben amyloid positron emission tomography scan showed increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex.

Conclusions

The patient of NPH was unresponsive to shunt therapy due to the development of AD.

Keywords: Hydrocephalus; Alzheimer Disease; Amyloid

INTRODUCTION

Normal pressure hydrocephalus (NPH), first reported by Hakim and Adams1 in 1965, manifests as a triad of gait disturbance, urinary incontinence, and dementia. Clinically, ventricular dilatation and normal cerebrospinal fluid (CSF) pressure are observed. NPH is one of the few causes of dementia that is potentially reversible.2

NPH can be classified into idiopathic and secondary types. Secondary NPH is associated with known etiologies, such as trauma, hemorrhage, infection, mass lesions.3 The first line treatment is to reduce CSF pressure via shunt placement, which often improves symptoms, in both secondary and idiopathic NPH. Furthermore, a reduction of CSF pressure via lumbar puncture can result in temporary improvement in symptoms.4

CSF shunt surgery does not always reduce the symptoms of NPH. The variable effectiveness is poorly understood. However, co-morbid neurodegenerative pathologies, such as Alzheimer's disease (AD), may play an important role.5 Indeed, several studies have shown the comorbidity of NPH and AD. 5, 6, 7

This report presents a case of NPH that was unresponsive to a ventriculoperitoneal (VP) shunt.

CASE REPORT

A 61-year-old, right-handed woman presented to the neurology clinic with a 5-year history of progressive gait difficulty and cognitive impairment. The patient complained of frequent falls after prolonged walking and short-term memory loss, while her recall of distant memories and visuospatial function were preserved. She reported urinary difficulties, such as urgency and incontinence. In summary, she had a gait disturbance that started around the age of 57, followed by cognitive impairment and urinary incontinence. She managed her activities of daily living without any problem. She had no family history of neurodegenerative disease. Neurological examination revealed a short-stepped, narrow-based non-ataxic gait. No other deficits were noted. Cognitive testing revealed a score of 28 out of 30 on the Mini-Mental State Examination (MMSE). Furthermore, her initial investigation, electrolyte levels and complete blood count were within the normal range, and renal and thyroid functions were within the normal limits. Magnetic resonance imaging (MRI) of the brain revealed ballooning of the ventricles (Fig. 1A). Lumbar puncture showed a normal opening pressure, which is consistent with normal-pressure hydrocephalus. The patient showed a marked improvement in gait after 50 mL of CSF was removed. Urinary incontinence and cognitive function showed improvement. Next, a VP shunt was inserted, which led to marked improvement in the patient's gait. Brain MRI was repeated after the operation, and no change in ventriculomegaly was noted.


Fig. 1
Brain magnetic resonance imaging at diagnosis and follow-up.

Fluid-attenuated inversion recovery images showed severe ventriculomegaly at diagnosis (A). There is no change in ventriculomegaly 9 years after insertion of the ventriculoperitoneal shunt (B).

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Nine years after the operation, at the age of 70, the patient began to experience frequent falls and a fracture to the shoulder. She underwent shoulder surgery and experienced post-operative delirium with disorientation and aggression. Following shoulder surgery, her gait, cognitive function, and urinary symptoms worsened over 6 months. There was no change in symptoms after valve pressure alteration on the VP shunt. Brain MRI did not reveal any indication of significant changes in the hydrocephalus (Fig. 1B). However, neuropsychological assessment showed deficits in memory, frontal/executive, and language domains with an MMSE score of 26. Furthermore, amyloid imaging with 18F-florbetaben positron emission tomography (PET) showed increased diffusion uptake in the bilateral cortices, precuneus, and the posterior cingulate cortex (Fig. 2). A diagnosis of AD was made and the anti-acetylcholinesterase inhibitor, donepezil, was prescribed to the patient.


Fig. 2
Axial images from amyloid imaging with 18F-florbetaben.

18F-florbetaben amyloid positron emission tomography scan showing increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex.

Click for larger imageDownload as PowerPoint slide

DISSCUSSION

NPH is an important cause of treatable dementia, however, there is considerable confusion regarding the clinical and radiographic criteria necessary to ensure a satisfactory outcome with CSF shunting procedures.8, 9

Estimates of the response rate to shunting in NPH vary widely.10 Disappointing results are often obtained when patients with NPH cannot be differentiated from those with AD, prompting the need for studies to distinguish between NPH and AD.

Non-demented NPH patients show specific patterns of executive impairment in neuropsychological tests, distinct from the deficits observed in patients with mild AD.11 Brain MRI reveals that the hippocampi are spared in NPH when compared with AD. Therefore, hippocampal volume is a potential diagnostic parameter to distinguish NPH from AD.12 18-fluorodeoxyglucose PET scans show bilateral temporoparietal hypometabolism in patients with AD, while NPH patients show global hypometabolism.13

Several studies show patients with comorbid NPH and AD.5-7 One study reported that 7 (33%) out of 21 patients with NPH exhibited neuropathological changes consistent with AD in cortical biopsy at the time of shunt placement.6 In another study, 31% - 50% of patients with NPH displayed AD-like neuropathology in cortical samples obtained at shunt implantation.7 A further study showed that 23 (42%) out of 55 patients who underwent biopsy at the time of shunt placement for NPH met the criteria for AD.5

Evidence suggests that CSF secretion and turnover clears toxic molecules, such as amyloid-peptides (Aβ), from the interstitial fluid space of the brain into the bloodstream. In NPH, elevated CSF pressure lowers CSF production resulting in less clearance of Aβ.14

In conclusion, we found that a lack of shunt response in our patient diagnosed with NPH was accompanied by AD pathology. Furthermore, noninvasive techniques that detect AD pathology, such as amyloid PET, facilitate the evaluation of NPH.

Notes

Conflict of Interest:The authors have no financial conflicts of interest.

Author Contributions:

  • Conceptualization: Kang MJ, Yi SH.

  • Data curation: Kang MJ, Park YH.

  • Formal analysis: Kang MJ, Park YH, Kim SY, Yi SH.

  • Investigation: Park YH, Kim SY.

  • Methodology: Park YH, Kim SY.

  • Project administration: Kang MJ, Yi SH.

  • Resources: Park YH.

  • Software: Yi SH.

  • Supervision: Park YH, Kim SY.

  • Validation: Park YH, Kim SY.

  • Visualization: Kang MJ, Yi SH.

  • Writing - original draft: Kang MJ, Yi SH.

  • Writing - review & editing: Kang MJ, Yi SH.

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