Two elderly patients with idiopathic normal pressure hydrocephalus diagnosed by head MRI and tap test

Dementia, gait disturbance and urinary incontinence were noted in two elderly patients, and diagnosed as idiopathic normal pressure hydrocephalus (iNPH). Case 1 was a 79‐year‐old man in whom dementia symptoms appeared 2 years ago. Gait disturbance and urge incontinence of urine developed later, and the patient visited our hospital. Walking was wide‐based and frozen gait was noted at the time of visiting our hospital. The mini‐mental state examination (MMSE) score was 11. A head MRI detected expansion of the cerebral ventricles and sylvian fissures, and narrowing of the cerebral fissures and the subarachnoid space in the higher convexity region. The diagnosis of iNPH was made based on the clinical symptoms and imaging findings, and a shunt operation (cerebrospinal fluid shunt) was performed in the neurosurgery department. Gait disturbance and cognitive function slightly improved after the operation. Case 2 was an 81‐year‐old woman who had had brachybasia for 1 year, and swayed from side to side while walking. Since disorientation and urge incontinence transiently occurred, the patient visited our hospital. The MMSE score was 24. Head MRI findings were similar to those in case 1. The cerebrospinal tap test was performed, and walking improved in the 1‐week course observation. iNPH is not very well recognized, compared to secondary NPH, and is likely to be overlooked because differentiation from Alzheimer's disease and vascular dementia based on symptoms and imaging is difficult in elderly patients. As iNPH is treatable by accurate diagnosis and therapy, the accumulation of cases indicated for shunt operation may be necessary.     

Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test

Idiopathic Normal Pressure Hydrocephalus (iNPH)—the leading cause of reversible dementia in aging—is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH‐specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer''s disease (AD). Here we investigate the resting‐state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer''s pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive‐control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD‐pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross‐network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.     

脑脊液引流试验对原发性正常压力性脑积水分流手术效果的预测

目的应用脑脊液引流试验(Tap试验)对原发性正常压力性脑积水(iNPH)病人进行术前评估,预测分流手术的有效性。方法前瞻性研究50例iNPH病人,先行Tap试验,5 d后行脑室-腹腔分流术(V-P分流术)。Tap试验前1 h、Tap试验后24 h及分流术后7 d分别对病人的神经功能进行评估。通过筛检试验统计分析评估Tap试验并预测iNPH病人分流手术的有效性。结果 Tap试验阳性31例,其中V-P分流术临床症状改善30例,未改善1例;Tap试验阴性19例,其中V-P分流术后症状改善6例,未改善13例。结果提示Tap试验对iNPH分流手术的灵敏度为83.3%,特异度92.9%,阳性预测率96.8%,阴性预测率68.4%。结论 Tap试验是理想的iNPH分流手术疗效的阳性预测指标。     

CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus

BACKGROUND - To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects. METHODS - Lumbar CSF concentrations of sulfatide, neurofilament protein light (NFL), total-tau (T-tau), hyperphosphorylated tau (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analysed. RESULTS - The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery. CONCLUSIONS - The most striking finding was the power of the combined pattern of NFL, P-tau, and Abeta42 in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly.     

Gait analysis in idiopathic normal pressure hydrocephalus--which parameters respond to the CSF tap test?

OBJECTIVES: Normal pressure hydrocephalus (NPH) is an often underestimated cause of hypokinetic gait disorders in the elderly. Diagnosing NPH is a complex problem, since many symptoms overlap with other neurological diseases. The purpose of the present study was to characterize the gait pattern in NPH quantitatively. Additionally, we analyzed the improvement of gait parameters following tapping of cerebrospinal fluid (CSF). METHODS: Gait analysis was performed in 10 patients and 12 age-matched healthy controls during overground and treadmill locomotion. RESULTS: Compared to healthy controls, patients with NPH walked significantly slower, with shorter and more variable strides and a somewhat lower cadence. The feet were not lifted to a normal height and the dorsal extension of the forefoot prior to heel-strike was insufficient. Balance-related gait parameters such as step width and the foot rotation angles were significantly increased in NPH, while their variability was lower. Only some gait parameters improved after tapping 30 ml CSF. Gait velocity increased by about 23% due to an increased stride length, while the cadence remained unchanged. Balance-related gait parameters and the foot-to-floor clearance during swing were not affected by the treatment. CONCLUSIONS: In conclusion, we found a triad of decreased stride length, decreased foot-to-floor clearance and a broad-based gait to be the typical features of the gait abnormality in NPH. Only the stride length improved following a diagnostic spinal tap. These results may help to more reliably diagnose the condition of NPH in a routine clinical setting.     

The CSF tap test in normal pressure hydrocephalus: evaluation time,reliability and the influence of pain

Background: The cerebrospinal fluid tap test (TT) is a diagnostic tool used to select patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. The procedure and the evaluation of the TT vary between centres. We aimed to describe the evaluation time after the TT, to assess the variability between repeated measurements, the interrater agreement of the gait tests chosen and finally to investigate whether pain affects the gait performance post‐TT. Methods: Forty patients (21 men and 19 women) under evaluation for iNPH underwent a TT. Standardized gait analyses were performed before and 2, 4, 6, 8 and 24 h after the TT and repeated twice on every occasion. Independent of each other, two investigators evaluated the quality of gait. At each assessment time, the patients graded headache and back pain on a visual analogue scale. Results: Twenty‐seven patients (15 men and 12 women) responded to TT. Improvements in gait speed and number of steps were significant at every assessment time post‐TT. The variability between two measurements was low (Intra class correlation coefficient = 0.97), and the inter‐rater agreement was good with a κ = 0.74. Pain correlated negatively with improvement in gait speed (r = ?0.40, P < 0.05). Conclusions: We suggest that the TT can be evaluated at any time within the first 24 h and should be repeated if the patient does not initially improve. Gait analysis appears reliable between two evaluators. Further, it is indicated that post‐lumbar puncture pain negatively affects the gait and should be minimized.     

Cognitive impairment in patients with idiopathic normal pressure hydrocephalus

Cognitive impairment in patients with idiopathic normal pressure hydrocephalous (iNPH) has not been clearly documented. We performed standardized neuropsychological assessments of 21 patients with iNPH and of 42 patients with Alzheimer's disease (AD) matched to the patients with iNPH 2:1 by age, sex, and Mini-Mental State Examination score. Compared with the AD group, the iNPH group scored significantly higher on the orientation subtest of the Alzheimer's Disease Assessment Scale and on the general memory and delayed recall subtests of the Wechsler Memory Scale-Revised (WMS-R), and significantly lower on the attention/concentration subtest of the WMS-R and on the digit span, arithmetic, block design and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised. The impairment of frontal lobe functions is disproportionately severe and memory impairment is disproportionately mild in patients with iNPH compared with AD. Recognition of these features contributes to an early diagnosis, which can lead to a better prognosis.     

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.     

Features of gait most responsive to tap test in normal pressure hydrocephalus

OBJECTIVE: To identify components of gait associated with a positive tap test (TT) in patients with idiopathic normal pressure hydrocephalus (iNPH). PATIENTS AND METHODS: Thirty-three patients with iNPH underwent clinical evaluation pre- and post-TT and were classified as responders (Rs) or non-responders (NRs). Elements of gait were assessed with a formal standardized Gait Scale and compared between groups. RESULTS: Analysis of pre/post-TT group differences revealed an interaction for Total Gait Score and Walking Score, with improvements in responders only. Total Gait Scores improved by 29% in the Rs and 4.85% in the NRs. Rs showed significant post-TT improvements on a timed 10m walk, turning, and balance. Tandem walking, turning, truck balance and start stop hesitation showed trends toward improvement. CONCLUSIONS: The classic features of gait often used in determining diagnosis of NPH (wide based stride, reduced foot-floor clearance, and small steps) were not helpful in identifying responders to the TT. Walking speed, steps for turning, and tendency towards falling were most likely to improve post-TT. These straightforward measures can readily be adapted into clinical practice to assist in determination of shunt candidacy.     

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus

Czosnyka Z, Owler B, Keong N, Santarius T, Baledent O, Pickard JD, Czosnyka M. Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.
Acta Neurol Scand: 2011: 123: 414–418.
© 2010 John Wiley & Sons A/S. Objective – Cerebrospinal fluid (CSF) pressure–volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)? Methods – We investigated 92 patients presenting with iNPH. Mean age was 73 (range 47–86). There were 60 men and 32 women. They all presented with gait disturbance and ventricular dilatation. Memory deficit occurred in 72% and urinary incontinence in 52% of patients. All patients underwent computerized CSF infusion tests. Sixty‐four shunted patients were available for follow‐up, and their improvement was expressed using the NPH score. Results – Mean intracranial pressure (ICP) was 10.1 ± 5.1 mmHg, and mean resistance to CSF outflow was 17.3 ± 5.2 mmHg/(ml/min). Mean duration of symptoms was 24 ± 19 months (range from 2 weeks to 86 months). Baseline ICP, magnitude of ICP pulse waveform, brain compliance and improvement after shunting (72% of patients improved) did not exhibit any dependency on the duration of symptoms. The resistance to CSF outflow showed a strong tendency to decrease in time with the duration of symptoms beyond 2 years (R = −0.702; P < 0.005). Conclusion – This is a preliminary observation, and it suggests that for patients with duration of symptoms longer than 2–3 years, the threshold for normal resistance to CSF outflow should be duration‐adjusted.     

CSF neurotransmitter metabolites and neuropsychiatric symptomatology in patients with normal pressure hydrocephalus

Patients with normal pressure hydrocephalus (NPH) may exhibit certain neuropsychiatric symptomatology, possibly related to alterations in central neurotransmitter activity. The aim of this study was to relate psychiatric distress, as expressed by the scores in the SCL-90 subscales, to CSF levels of the main metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA) in NPH patients. The metabolite levels were estimated in CSF samples taken during the tap test in 19 patients with probable NPH, and compared to 19 sex- and age-matched controls. Cognitive impairment was evaluated by the MMSE. Compared to controls, NPH patients had similar MHPG and 5-HIAA levels, and significantly elevated HVA levels, a notable difference from patients with dementias. There were no significant correlations of metabolite levels to the scores in the nine SCL-90 subscales. MMSE score was not related either to metabolite levels, or to the SCL-90 subscale scores. Patients scored higher than controls in most SCL-90 subscales, more pronounced being the difference in obsessive-compulsive symptomatology. Serotonergic neurotransmitter activity seems not to be altered in NPH patients, and this may explain the reported lack of beneficial effect of serotonergic drugs for obsessive-compulsive symptoms in NPH patients.     

Quantitative electroencephalography in idiopathic normal pressure hydrocephalus: relationship to CSF outflow resistance and the CSF tap-test

Quantitative electroencephalography from the occipito-parietal region, gait, and psychometric tests were performed in patients with idiopathic normal pressure hydrocephalus (NPH) before and after drainage of 40 ml CSF. The results were compared to those in demented controls. The EEG results were also analyzed with respect to possible correlations with clinical, CSF dynamics, and psychometric variables. Significant differences between NPH patients and demented controls were not found neither in baseline EEG variables nor regarding the CSF tap-test-related change in EEG. The EEG-response to the CSF tap-test did not often exceed the day-to-day test-retest variability. In NPH patients, EEG slowing (relative delta and theta power) correlated significantly with CSF outflow-resistance (p< 0.002). Relative theta power correlated with the Thurstone's Identical Forms test (p<0.05). Significant correlations between EEG and Bingley's Memory Test were found for the control group but not among NPH patients (p<0.05). Thus, EEG band-power variables seem to reflect some of the pathophysiology involved in idiopathic normal pressure hydrocephalus, particularly increased resistance to CSF outflow. The practical value of the presently applied EEG method in NPH-diagnosis and prognostic evaluation seems to be limited, however.     

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。     

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,...