特发性正常压力脑积水患者的认知功能损害

目的 通过系列神经心理学测试分析特发性正常压力脑积水(iNPH)患者认知功能损害的特点及各种测试方法对诊断的作用.方法 运用神经心理学测试方法对18例iNPH患者、20例轻度阿尔茨海默病(AD)患者和20名健康对照者进行记忆力、注意力、执行功能、视空间能力评估,同时用受试者工作特征曲线分析这些测试方法对iNPH诊断的敏感度和特异度.结果 与健康对照组比较,iNPH组和AD组的总体认知状态和各认知领域均有受损,差异均有统计学意义.iNPH组与AD组相比较[数值以中位数(四分位数间距)表示],在额叶功能评定量表评分[9.0(2.8)分与13.0(3.5)分]、言语流畅性测验评分[10.0(8.5)分与12.0(8.0)分]、斯特鲁普色词测验卡片A耗时数[65.0(20.8)s与52.0(24.5)s]、斯特鲁普色词测验卡片B耗时数[157.5(44.3)s与108.0(37.3)s]、斯特鲁普干扰量耗时数[68.5(67.0)s与50.0(25.8)s]、积木测试评分[5.0(3.3)分与6.5(3.5)分]方面差异均有统计学意义(Z =4.047、2.025、2.857、3.864、3.218、2.221,均P＜0.05),而AD评估量表中单词回忆和单词辨认、数字广度测验、画钟测验评分差异均无统计学意义.其中,斯特鲁普色词测验卡片A耗时数、斯特鲁普色词测验卡片B耗时数、斯特鲁普干扰量耗时数对iNPH诊断的受试者工作特征曲线下面积分别为0.874、0.929、0.869,敏感度和特异度分别为88.9％和75.0％,88.9％和85.0％,94.4％和72.5％.结论 iNPH患者亦有记忆力、执行功能、注意力、视空间能力损害,其中以执行功能障碍最为突出.另外,斯特鲁普色词测验对iNPH诊断具有很好的识别能力.     

Association between cognitive impairment and gait disturbance in patients with idiopathic normal pressure hydrocephalus

We compared the scores of the Frontal Assessment Battery (FAB), initial fluency subtest, category fluency subtest and subtests of the Mini-Mental State Examination (MMSE) between patients with idiopathic normal pressure hydrocephalus (iNPH) and age-, sex- and MMSE-matched patients with Alzheimer's disease (AD). In patients with iNPH, the time and number of steps required to go and come back a 10-meter distance were measured (Walking test) and the associations between the scores of the cognitive tests and the performance of the Walking test were evaluated. The scores of the FAB and initial fluency subtest in patients with iNPH were significantly lower than those in patients with AD. The scores of the FAB, initial fluency subtest and serial 7 subtest of the MMSE significantly correlated with the two scores of the Walking test in patients with iNPH. The present results indicate that frontal lobe functions were impaired in patients with iNPH and that cognitive impairment was closely associated with gait disturbance in patients with iNPH.     

Cognitive recovery in idiopathic normal pressure hydrocephalus after shunt.

OBJECTIVE: Evaluate long-term changes in cognition after ventriculoperitoneal shunt insertion in patients with idiopathic normal pressure hydrocephalus. BACKGROUND: Although studies have indicated that treatment of normal pressure hydrocephalus with ventriculoperitoneal shunt improves gait, effects of treatment on cognition have been inconsistent. Several studies have reported no significant improvement on neuropsychological tests in patients with idiopathic normal pressure hydrocephalus. Selection of candidates for shunt surgery using a trial of controlled spinal fluid drainage via lumbar catheter may result in more consistent improvement in cognition. DESIGN/METHODS: This was a prospective, longitudinal study of performance on neuropsychological tests before and 6 to 12 months after insertion of a ventriculoperitoneal shunt in 10 patients with idiopathic normal pressure hydrocephalus who showed improvement in at least 1 clinical symptom with temporary lumbar drainage. Nonparametric tests were used to evaluate change. RESULTS: Significant group improvements at follow-up were demonstrated on tests of verbal memory as well as in 1 test of psychomotor speed. Eight of 10 patients showed improvement by more than 1 standard deviation on at least 1 memory test. Six of 10 patients improved significantly on more than 50% of the tests administered. CONCLUSIONS: Patients with idiopathic normal pressure hydrocephalus who show clinical improvement (in any symptom) after lumbar drainage are likely to show significant long-term improvement in memory after ventriculoperitoneal shunt.     

特发性正常压力脑积水脑脊液标志物的变化

目的 探讨特发性正常压力脑积水（iNPH）病人脑脊液（CSF）磷酸化tau蛋白（p-tau）、总tau蛋白（t-tau）、转化生长因子-β1（TGF-β1）的变化。方法 前瞻性收集2018年6月至2020年2月经分流术临床确诊的16例iNPH为确诊组,同期行脑脊液释放试验无效的16例可疑iNPH为可疑组。采用酶联免疫吸附试验检测CSF中p-tau、t-tau、TGF-β1水平。结果 确诊组CSF中p-tau水平显著低于可疑组（P<0.01）,TGF-β1水平显著高于可疑组（P<0.01）。两组CSF中t-tau水平无统计学差异（P>0.05）。8例确诊iNPH术后7 d的CSF中p-tau、t-tau水平较术前均明显降低（P<0.05）,而TGF-β1水平与术前无统计学差异（P>0.05）。结论 本文结果提示CSF中p-tau、t-tau、TGF-β1在iNPH诊断、分流术效果评估中具有一定的作用。     

Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus

Introduction

It has still not been clearly established whether the cognitive deficits of idiopathic normal pressure hydrocephalus (iNPH) are caused by a disturbance in cerebrospinal fluid (CSF) dynamics or an underlying metabolic disturbance.

Objective

To identify the possible associations between biochemical markers, the neuroimaging characteristics, and cognitive deficits of patients undergoing investigations for possible iNPH.

Methods

A CSF sample obtained during a lumbar puncture from 10 patients with iNPH was analyzed for several biochemical markers (lactate, 8-isoprostane, vascular endothelial growth factor [VEGF], neurofilament heavy protein, glial fibrillary acidic protein, amyloid beta 1-42, and total tau). All patients underwent a battery of neuropsychological testing and imaging as part of their selection process for their suitability for CSF diversion surgical procedure. Volumetric analysis of imaging was carried out measuring the ventricular volume (VV), intracranial volume (ICV), periventricular lucencies, deep white matter hyperintensities, and white matter (WM) volume, as well as their ratios.

Results

A significant negative correlation of preoperative symptom duration and total tau levels (R = −0.841, P = .002) was found. There was a significant positive correlation (R = 0.648, P = .043) between the levels of VEGF and the VV/ICV ratio. There was a significant positive correlation of the levels of glial fibrillary acidic protein and the VV/deep white matter hyperintensities ratio (R = 0.828, P = .006). A significant negative correlation was observed between the levels of neurofilament heavy protein and the VV/ICV ratio (R = −0.657, P = .039) and the WM volume (R = −0.778, P = .023). Lactate levels were lower for patients performing in the normal range on the Recognition Memory Test for faces. Patients who performed better in the Recognition Memory Test words test had higher ICV volumes. All the patients in this study showed below normal performance when the subcortical function was assessed.

Conclusion

The positive correlation of VEGF with the severity of ventriculomegaly may indicate that this is because of the transmantle pressure gradient; this response may not be because of hypoxia but represents an attempt at neuroregeneration. The degree of reactive gliosis correlates inversely with the severity of WM lesions. Neuronal degeneration is negatively correlated with the volume of the WM in these patients. The small association of volumetry and the cognitive profile of these patients may be consistent with a direct biochemical disturbance being responsible for the cognitive deficit observed. Ongoing studies with set protocols for neuropsychological assessment and volumetric analysis are warranted to further elucidate on the preliminary results of the current study.     

Survival in treated idiopathic normal pressure hydrocephalus

Journal of Neurology - To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities,...     

Specific patterns of cognitive impairment in patients with idiopathic normal pressure hydrocephalus and Alzheimer's disease: a pilot study

OBJECTIVES: Eleven patients with idiopathic normal pressure hydrocephalus (NPH) were selected from an initial cohort of 43 patients. The patients with NPH fell into two distinctive subgroups: preshunt, group 1 (n=5) scored less than 24 on the mini mental state examination (MMSE) and were classified as demented and group 2 (n=6) scored 24 or above on the MMSE and were classified as non-demented. METHODS: All patients were neuropsychologically assessed on two occasions: preshunt and then again 6 months postshunt. Group 1 completed the mini mental state examination (MMSE) and the Kendrick object learning test (KOLT). In addition to the MMSE and KOLT, group 2 completed further tasks including verbal fluency and memory and attentional tasks from the CANTAB battery. Nine of the 11 patients also underwent postshunt MRI. RESULTS: Group 1, who, preshunt, performed in the dementing range on both the MMSE and KOLT, showed a significant postoperative recovery, with all patients now scoring within the normal non-demented range. Group 2, although showing no signs of dementia according to the MMSE and KOLT either preshunt or postshunt, did show a specific pattern of impairment on tests sensitive to frontostriatal dysfunction compared with healthy volunteers, and this pattern remained postoperatively. Importantly, this pattern is distinct from that exhibited by patients with mild Alzheimer's disease. Eight of the nine patterns of structural damage corresponded well to cognitive performance. CONCLUSIONS: These findings are useful for three main reasons: (1) they detail the structural and functional profile of impairment seen in NPH, (2) they demonstrate the heterogeneity found in this population and show how severity of initial cognitive impairment can affect outcome postshunt, and (3) they may inform and provide a means of monitoring the cognitive outcome of new procedures in shunt surgery.     

Postural function and subjective eye level in patients with idiopathic normal pressure hydrocephalus

Disturbance of posture is a frequent indication of idiopathic normal pressure hydrocephalus (iNPH) and is characterised by an increased sway in the frontal and sagittal planes. Further, iNPH patients with increased backward sway are known to have a defective perception of the subjective visual vertical (SVV), with the upper portion of an articulated rod tilted towards themselves. The objective of the present study was to compare subjective eye level (SEL) with actual eye level (EL) and compare this data with SVV and postural function. Twenty iNPH patients and ten normal controls estimated SEL by placing an adjustable horizontal line at EL. Sway pattern and SVV were also examined as previously described. The patients presented larger errors on downward as compared to upward line adjustments; all patients also presented a SVV tilted towards them. The patients swayed more in the sagittal than in the frontal plane at a higher speed than the normal controls, and they were relatively less helped by their vision. This is in accordance with the tendency to fall backwards seen in many iNPH patients. iNPH patients have a tendency to place SEL higher than EL and this, together with examination of SVV and sway pattern, suggests defective internal processing of gravicentric information.     

Self-reported functional outcome after surgical intervention in patients with idiopathic normal pressure hydrocephalus

The goal of this study was to characterize long-term social and functional outcomes in adults treated for idiopathic normal pressure hydrocephalus (NPH). Data for 252 patients treated medically or surgically for idiopathic NPH were obtained through the Hydrocephalus Association Database Project. Data on post-surgical outcomes including improvement in symptoms, the need for in-home care, ability to drive, and employment status were analyzed. Most patients (73.7%) surveyed were treated with a shunt, an endoscopic third ventriculostomy (ETV), or both. More patients who underwent surgery reported driving and being employed compared to those who did not have surgery. Most shunt patients had improvements in gait (81.1%), urinary incontinence (55.9%), and dementia (64.4%). Overall, shunt patients reported more dramatic improvements in quality of life as compared to ETV patients (72.2% versus 55.6%). Treating idiopathic NPH with cerebrospinal fluid diversion facilitates a return to independence through improved functional and social outcomes.     

Retrograde jugular flow associated with idiopathic normal pressure hydrocephalus

To clarify the relation between the drainage pathway of cerebrospinal fluid and the development of idiopathic normal pressure hydrocephalus (iNPH), we examined flow patterns of internal jugular veins in 20 patients with iNPH and 13 control patients using air-contrast ultrasound venography during the Valsalva maneuver. The iNPH group had a significantly greater frequency of retrograde jugular venous flow (19/20, 95%) than the control group (3/13, 23%) (chi(2) test, p < 0.001). Our results suggest that retrograde jugular venous flow may be associated with the development of iNPH; therefore, the analysis of retrograde jugular venous flow could be a useful element in the diagnosis of iNPH.     

Altered glymphatic system in idiopathic normal pressure hydrocephalus

ObjectiveTo assess the glymphatic activity in patients with idiopathic normal pressure hydrocephalus (NPH) using the “Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS)” method, and determine the feasibility of non-invasive MRI for the evaluation of the glymphatic function.MethodsBetween April 2017 and March 2019, 16 patients diagnosed with NPH and 16 age- and sex-matched controls were included. On 3T DTI-MRI, the diffusivities along x-, y-, and z-axes were measured, and the ALPS-index – a ratio that accentuated water diffusion along the perivascular space – was calculated by two independent readers. The inter-observer agreement was tested using the interclass correlation coefficient. The differences in the diffusivities and the ALPS-index between the NPH and control groups were compared using the Mann-Whitney test. The values were also compared according to the treatment response to the cerebrospinal fluid drainage and correlated with the callosal angle using a correlation coefficient.ResultsThe inter-observer agreements were excellent for the diffusivities and the ALPS-index. The diffusivity along the x-axis in the projection fibers area and the ALPS-index were significantly lower in patients with NPH (median, 0.556/1.181) than in the controls (0.610/1.540), respectively (P = 0.032/< 0.0001). The ALPS-index was significantly lower in the NPH group who did not show treatment response than those who showed symptomatic relief (0.987/1.329; P < 0.0001). The ALPS-index showed a significant positive correlation with the callosal angle (r = 0.82, P = 0.0001).ConclusionsThe DTI-ALPS method can be a useful imaging tool for identifying glymphatic dysfunction and for individually quantifying glymphatic activity in patients with NPH.     

Caudate structural abnormalities in idiopathic normal pressure hydrocephalus

BACKGROUND - Idiopathic normal pressure hydrocephalus (iNPH) is a reversible dementia in which fronto-striatal cognitive deficits and apathy may be present. OBJECTIVES - The study investigated structural volumetric changes in iNPH, apart from ventriculomegaly. MATERIALS AND METHODS - A full-brain voxel-based morphometric analysis between 11 iNPH patients and 14 healthy controls identified regions of interest (ROIs) for manual volumetric analyses. RESULTS - Caudate and corpus callosum ROI measurements revealed diminished caudate nuclei volume in the iNPH group. CONCLUSIONS - The role of the caudate nucleus in cognitive and affective changes in iNPH should now be explored.     

Correlation of midbrain diameter and gait disturbance in patients with idiopathic normal pressure hydrocephalus

Background and purpose Although gait disturbance is an important feature of idiopathic normal pressure hydrocephalus (NPH), only tentative theories have been offered to explain its pathophysiology. It has been suggested that the mesencephalic locomotor region is the anatomical substrate for the development of the hypokinetic NPH gait. To investigate this possibility, we evaluated the correlation between gait disturbance and midbrain diameter. Methods We enrolled 21 patients with NPH and 20 age–matched control subjects for the study. The maximal diameter of the midbrain and pons, and the width of the lateral and third ventricles were measured using midsagittal T1–weighted MRI and axial T2–weighted MRI, respectively. Gait disturbance, cognitive dysfunction, and incontinence were semiquantified. Results The maximal midbrain diameter was significantly smaller in the NPH group than in the controls (14.8 ± 0.9 vs. 17.1 ± 0.7mm, p < 0.001). There were inverse correlations between the midbrain diameter and the widths of the two ventricles (r = –0.562, p = 0.008 for the third ventricle, and r = –0.510, p = 0.018 for the lateral ventricle). The severity of gait disturbance was negatively correlated with the midbrain diameter (r = –0.598, p = 0.004), but the degree of cognitive dysfunction and incontinence showed no significant correlation with midbrain diameter or ventricular width. Conclusions This study suggests that midbrain atrophy is significantly associated with gait disturbance in NPH.     

Cognitive impairment in normal pressure hydrocephalus (NPH). A proposal for clinical evaluation protocol

Normal pressure hydrocephalus (NPH) is characterized by gait disturbance, urinary incontinence and dementia, and is associated with variable ventricular enlargement. The most accepted treatment of NPH is the placement of a cerebrospinal fluid shunt. Owing to the characteristics of the patients and the invasive nature of the surgical treatment, it is fundamental to detect those patients who could obtain a greater benefit from the treatment. Neuropsychological assessment of these patients could significantly contribute to a better diagnosis of NPH, determining a cognitive deterioration profile for these patients, allowing the assessment of treatment efficacy and helping to detect other additional causes of dementia. The aim of this study is to describe the cognitive deterioration profile of NPH patients and to present the clinical, functional and neuropsychological assessment protocol used in our hospital.     

特发性正常压力脑积水的诊断研究进展

特发性正常压力脑积水(idiopathic normal pressure hydrocephalus,iNPH)是1965年最先提出的一种以步态异常、痴呆和尿失禁(又称Hakim三联征)为特征的交通性脑积水综合征.挪威流行病学调查估计iNPH在人群中的发病率为5.5/10万人口,患病率为21.9/10万人口[1].日本的研究表明iNPH主要发生于老年人,65岁以上患病率为1.4％～2.9％[2-3],被认为是痴呆的第一位可治性病因,脑脊液分流术可使半数以上患者症状改善[4-5].因iNPH的临床和影像学表现与其它疾病相似,早期诊断比较困难,但早期干预可获得好的疗效.随着研究深入,一些新的诊断依据不断发现,本文就有关研究进展做一综述.     

Evaluation of autonomic malfunction in idiopathic normal pressure hydrocephalus

OBJECTIVE: The autonomic nervous system plays an important role in urinary disturbance which is one of the main symptoms of idiopathic normal pressure hydrocephalus (iNPH); thus, the focus of the present study was to identify the autonomic function parameters that would be useful as clinical indicators of iNPH. METHODS: The subjects consisted of 18 iNPH patients (group N) and 31 normal controls (group C). Before and after a lumbar puncture test, they were examined for CVR-R and total heart rate. A power spectral analysis of R-R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Urinary incontinence was evaluated using the overactive bladder symptom score (OABSS) questionnaire and bladder capacity. Correlations between the above indicators and clinical indicators of iNPH, such as the mini-mental state examination and the Evans index, were examined. RESULTS: The HF values (ms(2)) were 190.3 in group C and 237.2 in group N; the difference was statistically significant. In group N, the HF value after the lumbar puncture test was lower (160.3) than the value before the lumbar puncture test, confirming that the increased parasympathetic state returned to a near normal level after CSF drainage. A significant positive correlation was noted only between the pre-lumbar puncture HF value and the OABSS. CONCLUSION: iNPH is associated with increased parasympathetic activity, and the lumbar puncture test and shunt surgery may correct this autonomic imbalance to near normal levels.     

Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH), the most common type of adult‐onset hydrocephalus, is a potentially reversible neuropsychiatric entity characterized by dilated ventricles, cognitive deficit, gait apraxia, and urinary incontinence. Despite its relatively typical imaging features and clinical symptoms, the pathogenesis and pathophysiology of iNPH remain unclear. In this review, we summarize current pathogenetic conceptions of iNPH and its pathophysiological features that lead to neurological deficits. The common consensus is that ventriculomegaly resulting from cerebrospinal fluid (CSF) dynamics could initiate a vicious cycle of neurological damages in iNPH. Pathophysiological factors including hypoperfusion, glymphatic impairment, disturbance of metabolism, astrogliosis, neuroinflammation, and blood‐brain barrier disruption jointly cause white matter and gray matter lesions, and eventually lead to various iNPH symptoms. Also, we review the current treatment options and discuss the prospective treatment strategies for iNPH. CSF diversion with ventriculoperitoneal or lumboperitonealshunts remains as the standard therapy, while its complications prompt attempts to refine shunt insertion and develop new therapeutic procedures. Recent progress on advanced biomaterials and improved understanding of pathogenesis offers new avenues to treat iNPH.