Outcome predictors in patients with normal pressure hydrocephalus]

Despite the accumulation of knowledge over the years, the postoperative results of shunt implantation in patients with normal pressure hydrocephalus (NPH) have shown little improvement. This means that reliable predictors of the course of the disease need to be identified. In a prospective study carried out between 1982 and 2000 we re-examined 155 (78%) of 200 NPH patients treated by shunt implantation, 7 months after their operation. On the basis of the results of the intrathecal infusion test NPH was graded early stage (no brain atrophy) or late stage (brain atrophy). We looked at the following factors as possible predictors: patient's age, disease duration, idiopathic or secondary aetiology, clinical signs such as gait ataxia, dementia and urinary incontinence, results of spinal tap, valve type and valve infection, and resistance to cerebral spinal fluid outflow and postoperative changes in ventricular size. As a measure for outcome we used the NPH recovery rate, and the Pearson chi-square test for statistical evaluation. 80 patients with early stage NPH, a history < 1 year, absence of dementia and an implanted Miethke dual-switch valve proved to be significant predictors of a positive outcome. Outflow resistance proved to have only minimal impact on outcome. The 75 patients with late-stage NPH had better outcome when dementia was absent, outflow resistance was > 20 mmHgmin/ml, the CSF tap test was positive, and a Miethke dual-switch valve was implanted.     

The grading of normal pressure hydrocephalus.

PATIENTS AND METHOD: During a period of 15 years we investigated 200 patients suspected of normal pressure hydrocephalus (NPH) by means of an intrathecal infusion test. In 107 patients (54%) the diagnosis of a normal pressure hydrocephalus could be confirmed. For the evaluation of the course of disease we used the Black-Grading-Scale for shunt assessment [1] and the clinical grading for chronic hydrocephalus (Kiefer-scale) [4] pre- and postoperatively as well as in a follow-up examination seven months after surgical treatment. The aim of our study was to find out a quick and easy-to-handle bed-side examination for the grading of NPH. DISCUSSION: The Black-Grading-Scale does not allow to distinguish between patients in an unchanged condition and those with a worsening of their symptoms. Therefore this scale is useful for patients with an obstructive hydrocephalus but not for those with a NPH. In our opinion the clinical grading of Kiefer [4] seems to be the most reliable scale for the grading and long term follow-up of a normal pressure hydrocephalus. CONCLUSION: Our own created NPH-Recovery-Rate is based on the clinical grading for chronic hydrocephalus (Kiefer-scale) [4]. It allows the interindividual comparison between the courses of disease in patients with normal pressure hydrocephalus.     

Pressure-dependent flow resistance in craniospinal cerebrospinal fluid dynamics: a calculation model for diagnosis of normal pressure hydrocephalus]

Computer-aided processing of the results obtained with the intrathecal infusion test using our newly developed mathematical model simplifies the investigation technique and thus the diagnosis of normal pressure hydrocephalus. Simultaneous determination of resistance and compliance in a single session markedly reduces the examination-related stress on the patient. In contrast to the classical methods, the new calculation does not require the ICP to reach a plateau. Unlike the static approach, our model describes the functional pressure-dependent course of the resistance. This means that account is taken of the non-linearity of the CSF dynamics during the processing of the biosignal. The intrathecal infusion test used to measure resistance and compliance is a reliable diagnostic method in patients with a normal pressure hydrocephalus.     

What Do Physicians Know About Normal Pressure Hydrocephalus and When Did They Know It? A Survey of 284 Physicians

Normal pressure hydrocephalus (NPH) is a relatively new neurologic disorder first described by Salamon Hakim of Bogotá, Colombia, in 1965. NPH is characterized by three symptoms — impaired gait, incontinence and dementia — and an anatomic abnormality, i.e., enlargement of the cerebral ventricles, which can be seen on computerized tomographic or magnetic resonance imaging. Surprisingly, the intracranial pressure is normal.     

Brain metabolism in adult chronic hydrocephalus

Normal pressure hydrocephalus (NPH) is the most frequent form of chronic hydrocephalus in adults. NPH remains underdiagnosed although between 5% and 10% of all demented patients may suffer from this disorder. As dementia is an increasing demographic problem, treatable forms such as in NPH have become a central issue in neurology. Despite the traditional perception of hydrocephalus being a disorder of disturbed CSF dynamics, in NPH metabolic impairment seems at least as important. So far, the only valid animal model of NPH is chronic adult kaolin hydrocephalus. In this model, opening of alternative CSF outflow pathways leads to normal or near-normal intracranial pressure and CSF outflow resistance. Yet, various metabolic disturbances cause ongoing ventricular enlargement and characteristic symptoms including cognitive decline and gait ataxia. Delayed hippocampal neuronal death, accumulation of beta-amyloid and disturbed cholinergic neurotransmission may contribute to memory dysfunction. Compromised periventricular blood flow, decreased dopamine levels in the substantia nigra and damaged striatal GABAergic interneurons may reflect basal ganglia symptoms. At least in human hydrocephalus cerebrovascular co-morbidity of the white matter plays an important role as well. It seems that in hydrocephalus from a certain 'point of no return' metabolic impairment becomes decoupled from CSF dynamics and, at least partly, self-sustained. This is probably the reason why despite restored CSF circulation by shunting many patients with chronic hydrocephalus still suffer from severe neurological deficits. The present paper offers a comprehensive review of the experimental and clinical data suggesting metabolic disturbances in chronic hydrocephalus.     

Neurochemical Changes in the Cerebral Cortex of Treated and Untreated Hydrocephalic Rat Pups Quantified with In Vitro 1H-NMR Spectroscopy

Abstract: The pathophysiology of infantile hydrocephalus is poorly understood, and shunt treatment does not always lead to a normal neurological outcome. To investigate some of the neurochemical changes in infantile hydrocephalus and the response to shunt treatment, we have used high-resolution ¹H-NMR spectroscopy to analyze extracts of cerebral cortex from H-Tx rats, which have inherited hydrocephalus with an onset in late gestation. Hydrocephalic rats and rats with shunts placed at either 4 or 12 days after birth were studied at 21 days after birth, together with age-matched control littermates. In hydrocephalic rats there was a 46–62% reduction in the following compounds: myo -inositol, creatine, choline-containing compounds, N -acetyl aspartate, taurine, glutamine, glutamate, aspartate, and alanine. Phosphocreatine, glycine, GABA, and lactate were also reduced but not significantly. These changes are consistent with neuronal atrophy rather than ischemic damage. In hydrocephalic rats that received shunt treatment at 4 days, there were no significant reductions in any chemicals, indicating a normal complement of neurons. However, some compounds, particularly taurine, were elevated above control. After treatment at 12 days, N -acetyl aspartate and aspartate remained significantly reduced, suggesting continued neuronal deficiency.     

Measurement of the blood flow velocity in the pericallosal artery of children with hydrocephalus by transcranial Doppler ultrasonography--preliminary results

AIM: The goal of this study was to evaluate selected parameters of the Doppler curve of the pericallosal artery at children with hydrocephalus. METHODS: 12 patients with hydrocephalus were divided into two groups. Group 1 comprised children needing cerebrospinal fluid drainage, and group 2 comprised children without any indication for drainage or with an already inserted well-functioning drainage system. Dilatation of the cerebral ventricles was determined by transcranial ultrasonography. Following parameters of a blood flow of the pericallosal branch of the anterior cerebral artery: peak systolic blood flow velocity (PSFV), end-diastolic blood flow velocity (EDFV) and resistive index (RI) were observed by transcranial Doppler ultrasonography. Parameters of The Doppler curve were measured without pressure (baseline parameters) and during compression of the anterior fontanelle (pressure provocation test). RESULTS: Group 1: baseline parameters: PSFV 68.9 +/- 13.52 cm/s, EDFV 18.26 +/- 10.39 cm/s, RI 0.76 +/- 0.12; parameters during pressure provocation test: PSFV 66.92 +/- 19.75 cm/s, EDFV 10.88 +/- 11.18 cm/s, RI 0.86 +/- 0.14. Group 2: baseline parameters: PSFV 59.95 +/- 19.38 cm/s, EDFV 20.65 +/- 8 cm/s, RI 0.65 +/- 0.04; parameters during the pressure provocation test: PSFV 57.14 +/- 18.91 cm/s, EDFV 17.7 +/- 8.3 cm/s, RI 0.68 +/- 0.05. CONCLUSION: The results show increased baseline and postcompressive values of RI of pericallosal artery in infants with hydrocephalus before drainage procedure and normal values of RI at children without the need for cerebrospinal fluid drainage or with a well-functioning drainage system.     

Ventricle equilibrium position in healthy and normal pressure hydrocephalus brains using an analytical model

The driving force that causes enlargement of the ventricles remains unclear in case of normal pressure hydrocephalus (NPH). Both healthy and NPH brain conditions are characterized by a low transparenchymal pressure drop, typically 1 mm Hg. The present paper proposes an analytical model for normal and NPH brains using Darcy's and Biot's equations and simplifying the brain geometry to a hollow sphere with an internal and external radius. Self-consistent solutions for the large deformation problem that is associated with large ventricle dilation are presented and the notion of equilibrium or stable ventricle position is highlighted for both healthy and NPH conditions. The influence of different biomechanical parameters on the stable ventricle geometry is assessed and it is shown that both CSF seepage through the ependyma and parenchymal permeability play a key role. Although very simple, the present model is able to predict the onset and development of NPH conditions as a deviation from healthy conditions.     

A clinical,pneumoencephalographic and radioisotopic study of normal-pressure communicating hydrocephalus

Human serum albumin labelled with iodine-133 or technetium-99^m was injected by the lumbar or cisternal route into patients suspected of having communicating hydrocephalus, and scintigrams were performed up to 24 hours after injection.The CSF isotope studies were shown to be a valuable adjunct to clinical examination and pneumoencephalography in the diagnosis of hydrocephalus. This was especially true in suspected cases of “normal”-pressure hydrocephalus where there may be considerable uncertainty as to which patients with normal pressure and enlarged ventricles will benefit from a shunting procedure. The CSF isotope study provides useful information to the clinician in differentiating patients with symptomatic hydrocephalus from the larger group with dementia, cerebral atrophy and hydrocephalus ex vacuo.     

Longitudinal Evaluation of an N-Ethyl-N-Nitrosourea-Created Murine Model with Normal Pressure Hydrocephalus

Background

Normal-pressure hydrocephalus (NPH) is a neurodegenerative disorder that usually occurs late in adult life. Clinically, the cardinal features include gait disturbances, urinary incontinence, and cognitive decline.

Methodology/Principal Findings

Herein we report the characterization of a novel mouse model of NPH (designated p23-ST1), created by N-ethyl-N-nitrosourea (ENU)-induced mutagenesis. The ventricular size in the brain was measured by 3-dimensional micro-magnetic resonance imaging (3D-MRI) and was found to be enlarged. Intracranial pressure was measured and was found to fall within a normal range. A histological assessment and tracer flow study revealed that the cerebral spinal fluid (CSF) pathway of p23-ST1 mice was normal without obstruction. Motor functions were assessed using a rotarod apparatus and a CatWalk gait automatic analyzer. Mutant mice showed poor rotarod performance and gait disturbances. Cognitive function was evaluated using auditory fear-conditioned responses with the mutant displaying both short- and long-term memory deficits. With an increase in urination frequency and volume, the mutant showed features of incontinence. Nissl substance staining and cell-type-specific markers were used to examine the brain pathology. These studies revealed concurrent glial activation and neuronal loss in the periventricular regions of mutant animals. In particular, chronically activated microglia were found in septal areas at a relatively young age, implying that microglial activation might contribute to the pathogenesis of NPH. These defects were transmitted in an autosomal dominant mode with reduced penetrance. Using a whole-genome scan employing 287 single-nucleotide polymorphic (SNP) markers and further refinement using six additional SNP markers and four microsatellite markers, the causative mutation was mapped to a 5.3-cM region on chromosome 4.

Conclusions/Significance

Our results collectively demonstrate that the p23-ST1 mouse is a novel mouse model of human NPH. Clinical observations suggest that dysfunctions and alterations in the brains of patients with NPH might occur much earlier than the appearance of clinical signs. p23-ST1 mice provide a unique opportunity to characterize molecular changes and the pathogenic mechanism of NPH.     

蛛网膜下腔出血合并脑积水的治疗方法探讨

目的:探讨蛛网膜下腔出血(SAH)合并脑积水的治疗方法。方法:回顾性分析31例SAH合并脑积水患者的临床资料,除常规脱水、防治血管痉挛、营养神经等治疗方法外,其中10例给予行脑室-腹腔分流术,21例行侧脑室外引流术,对比分析两种治疗方案的利弊。结果:10例脑室-腹腔分流术患者9例手术效果良好,术后复查颅脑CT显示脑室明显减小,间质水肿消失,1例患者术后1月内再次出现脑积水,给予行同侧分流管探查再通、对侧脑室-腹腔分流术,术后效果良好,颅脑CT示脑室减小。21例行侧脑室外引流术患者,术后感染2例,全部患者均术后7天内拔除引流管,术后1月9例复发脑积水,给予再次行脑室-腹腔分流术,术后效果良好。结论:在手术指征明确的情况下,早期给予SAH合并脑积水患者行脑室腹腔分流术,分流管堵塞可能性小,术后感染发生率低,临床效果令人满意。     

Patients with Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases Have Increased Levels of Neurofilament Protein in CSF

Abstract: In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well-characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743 ± 1,661 ng/L; mean ± SD) and AD (346 ± 176 ng/L) compared with controls (138 ± 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 ± 237 ng/L) than those with signs of upper motor neuron disease (2,435 ± 1,633 ng/L) ( p < 0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 ± 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.     

Diagnosis of progressive open internal hydrocephalus in patients after cranio-cerebral injuries and subarachnoid hemorrhage]

Late internal hydrocephalus has been diagnosed in 68 (44%) out of 154 patients treated for the ruptured cerebral aneurysms, and in 37 (31%) out of 120 patients, who underwent cranio-cerebral trauma. To establish the indications for shunts, CT scans of the skull, tomoventriculography, and infusion tests have been carried out in 38 patients. It has been found, that increased transparency of the areas below cerebral ependyma, the lack of cerebral cortex sulci, and imaging of the temporal horns together with internal hydrocephalus in CT scans indicate an active process and are indications to shunting. If there are no signs of active process in CT scans despite of the presence of hydrocephalus, tomoventriculography should be performed to establish more fully the indications to shunting.     

脑室镜和腹腔镜辅助脑室腹腔分流术治疗老年脑积水的疗效

目的:探讨脑室镜和腹腔镜辅助脑室腹腔分流术治疗老年脑积水的疗效。方法:选择我院90例老年脑积水患者,按随机数字表法平均分为A、B、C 3组各30例,A组患者给予传统脑室腹腔分流术治疗,B组患者给予腹腔镜辅助下脑室腹腔分流术治疗,C组患者给予脑室镜和腹腔镜综合辅助下脑室腹腔分流术治疗,比较3组患者治疗有效率及术后并发症发生率。结果:C组患者治疗有效率为90.0%,明显高于A组63.3%及B组76.7%,比较差异具有统计学意义(均P0.05);C组患者术后感染及分流管堵塞并发症发生率明显低于A组和B组,比较差异均有统计学意义(均P0.05);B组和C组脑实质内出血发生率均低于A组,与A组比较差异具有统计学意义(P0.05)。结论:脑室镜和腹腔镜综合辅助下脑室腹腔分流术治疗老年脑积水的疗效显著,术后并发症少,值得推广。     

The pathogenesis of normal pressure hydrocephalus: A theoretical analysis

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles, usually caused by impaired absorption of the fluid into the bloodstream. Despite obstructed absorption and continued secretion of CSF into the ventricles at a near normal rate, the ventricular CSF pressure (VCSFP) is often normal. We attempt to understand how hydrocephalus can exist with normal VCSFP by exploring the role of the brain parenchyma in absorbing CSF in hydrocephalus. We test three theories: (1) the ventricular wall is impermeable to CSF; (2) ventricular CSF seeps into the parenchyma, from which it is efficiently absorbed; and (3) ventricular CSF seeps into the parenchyma but is absorbed inefficiently. We model the brain as a thick spherical shell consisting of a porous, elastic, solid matrix, containing interstitial fluid and blood. We modify the equations of poroelasticity, which describe flow of fluid through porous solids, to allow for parenchymal absorption. For each of the three theories we calculate the steady state changes in VCSFP and in parenchymal fluid pressure caused by an incremental defect in CSF absorption. We also calculate the steady state changes in fluid content, tissue volume, tissue displacement, and stresses caused by a small increment of VCSFP. We conclude that only the second theory—seepage of CSF with efficient parenchymal absorption—accounts for the clinical features of normal pressure hydrocephalus. These features include sustained ventricular dilatation despite normal VCSFP, increased periventricular fluid content, and localized periventricular white matter damage.     

Increased CSF levels of somatostatin in patients with brain tumours and intracranial hypertension

The cerebrospinal fluid (CSF) levels of somatostatin in patients with brain tumours, communicating hydrocephalus, lumbar-disc disease (treated as a control) were measured by specific radioimmunoassay. The somatostatin concentration in the patients with brain tumours and intracranial hypertension was significantly higher compared to those with brain tumours and normal CSF pressure. CSF somatostatin content in patients with communicating hydrocephalus, was similar to patients with brain tumours and normal CSF pressure, and did not show a significant difference from the control group. The authors discuss possible reasons for such results obtained in patients with brain tumours and intracranial hypertension.     

Deficiencia visual y neurológica posterior a la disfunción del sistema de derivación ventrículo-peritoneal: reporte de caso

Neurological visual impairments in children have multiple causes, some of them reversible while others are not. Hydrocephalus is one of the most important and common ones as it can result in permanent impairment. There are multiple causes of hydrocephalus, intraventricular hemorrhage being the main one. This generally occurs when the germinal matrix bleeds and is very common in preterm newborns.We present the clinical case of a patient with cerebral palsy, intraventricular hemorrhage, and hydrocephalus as a result of a preterm multiple pregnancy who developed optic atrophy during childhood secondary to ventricle-peritoneal shunt dysfunction. During the rehabilitation and treatment period, she received neurorehabilitation sessions, which improved her visual acuity and capacity. We found similarities and differences with other cases and we confirmed the importance of the treatment chosen for the recovery of visual capacity.     

Effect of synthetic 1-34 fragment of human parathyroid hormone on plasma adenosine 3',5'-monophosphate (cAMP) concentrations and the diagnostic criteria based on the plasma cAMP response in Ellsworth-Howard test

The effect of synthetic 1-34 fragment of human parathyroid hormone (hPTH(1-34] on plasma adenosine 3',5'-monophosphate (cAMP) in human subjects and the diagnostic criteria for the plasma cAMP response in an Ellsworth-Howard test were studied. 20 or 30 micrograms hPTH(1-34) and 200 USP Parathormone (Eli Lilly & Co.), infused intravenously over 5 min, produced very similar patterns of response in plasma cAMP, peak values being observed within 5 or 10 min after the end of the infusion. The maximum levels of plasma cAMP were over 111.5 pmol/ml in all of the normal subjects (n = 5) and patients with idiopathic hypoparathyroidism (n = 22), including those of children, but the plasma cAMP did not rise above 65.0 pmol/ml in pseudohypoparathyroidism (n = 7). There existed a significant correlation between the maximum plasma cAMP concentrations and increases in urinary cAMP excretion after infusions of both hPTH(1-34) and Parathormone. These results suggest that hPTH(1-34) has effects essentially identical to those of native PTH on plasma cAMP. We would like to propose a new diagnostic criterion in the Ellsworth-Howard test: a peak value of plasma cAMP over 100 pmol/ml after 30 micrograms hPTH(1-34) infusion is regarded as a normal response.     

A one-year, randomised, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with type 2 diabetes.

AIMS: The aim of the trial was to compare the efficacy and safety of the new, long-acting basal insulin, insulin glargine (LANTUS(R)), with NPH human insulin, each administered in a combination regimen with oral antidiabetic drugs in patients with Type 2 diabetes. METHODS: In a multicentre, open, randomised study, 570 patients with Type 2 diabetes, aged 34 - 80 years, were treated for 52 weeks with insulin glargine or NPH insulin given once daily at bedtime. Previous oral antidiabetic therapy was continued throughout the study. RESULTS: There was a clinically relevant decrease in glycosylated haemoglobin (GHb) values from baseline to endpoint with both drugs (insulin glargine: - 0.46 %; NPH insulin: - 0.38 %; p = 0.415); also, this difference was statistically significant in the subgroup of overweight patients with BMI > 28 kg/m 2 (insulin glargine: - 0.42 %, NPH insulin: - 0.11 %; p = 0.0237). Over the entire treatment period, NPH insulin-treated patients (41 %) and insulin glargine-treated patients (35 %) experienced a similar level of symptomatic hypoglycaemia. A statistically significant difference was observed in the number of patients treated with NPH insulin who reported at least one episode of nocturnal hypoglycaemia compared with those treated with insulin glargine in the overall population and in the overweight subgroup (overall: 24 % vs. 12 %, p = 0.002; overweight: 22.2 % vs. 9.5 %, p = 0.0006), using the Cochran-Mantel-Haenszel test. These differences were most pronounced in insulin-na?ve and overweight (BMI > 28 kg/m 2) sub-groups. The incidence of adverse events was similar for the two treatments. CONCLUSIONS: This study demonstrated that insulin glargine is as effective as NPH insulin in achieving glycaemic control in patients with Type 2 diabetes, and is associated with fewer episodes of symptomatic hypoglycaemia, particularly nocturnal episodes.