Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus.

Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.

Choroidal fissure acts as an overflow device in cerebrospinal fluid drainage: morphological comparison between idiopathic and secondary normal-pressure hydrocephalus.

To clarify the pathogenesis of two different types of adult-onset normal-pressure hydrocephalus (NPH), we investigated cerebrospinal fluid distribution on the high-field three-dimensional MRI. The subarachnoid spaces in secondary NPH were smaller than those in the controls, whereas those in idiopathic NPH were of similar size to the controls. In idiopathic NPH, however, the basal cistern and Sylvian fissure were enlarged in concurrence with ventricular enlargement towards the z-direction, but the convexity subarachnoid space was severely diminished. In this article, we provide evidence that the key cause of the disproportionate cerebrospinal fluid distribution in idiopathic NPH is the compensatory direct CSF communication between the inferior horn of the lateral ventricles and the ambient cistern at the choroidal fissure. In contrast, all parts of the subarachnoid spaces were equally and severely decreased in secondary NPH. Blockage of CSF drainage from the subarachnoid spaces could cause the omnidirectional ventricular enlargement in secondary NPH.

Magnetic Resonance Imaging of Normal Pressure Hydrocephalus.

Normal pressure hydrocephalus (NPH) is a syndrome found in the elderly, which is characterized by ventriculomegaly and deep white matter ischemia (DWMI) on magnetic resonance imaging (MRI) and the clinical triad of gait disturbance, dementia, and urinary incontinence. NPH has been estimated to account for up to 10% of cases of dementia and is significant because it is treatable by ventriculoperitoneal shunting. Patients with a known cause of chronic communicating hydrocephalus, that is, meningitis or hemorrhage, tend to respond better than patients with the so-called "idiopathic" form, most likely because of poor selection criteria in the past. Good response to shunting has been associated with hyperdynamic cerebrospinal fluid (CSF) flow through the aqueduct. In the early days of MRI, patients with a large CSF flow void extending from the foramen of Monro through the aqueduct to the fourth ventricle had an excellent chance of responding to ventriculoperitoneal shunting (P < 0.003). Today, we use phase-contrast MRI to measure the volume of CSF flowing through the aqueduct in either direction over a cardiac cycle. When this aqueductal CSF stroke volume is sufficiently elevated, there is an excellent chance of shunt responsiveness (100% positive predictive value in 1 study). Idiopathic NPH appears to be a "two-hit" disease-benign external hydrocephalus (BEH) in infancy followed by DWMI in late adulthood. As BEH occurs when the sutures are still open, these infants present with large heads, a finding also noted in patients with NPH. Although BEH has been attributed to immature arachnoidal granulations with decreased CSF resorptive capacity, this now appears to be permanent and may lead to a parallel pathway for CSF resorption via the extracellular space of the brain. With DWMI, the myelin lipid is lost, exposing the polar water molecules to myelin protein, increasing resistance to CSF outflow and leading to backing up of CSF and hydrocephalus.

Posturography in differential diagnosis of normal pressure hydrocephalus and brain atrophy.

Differentiation between normal pressure hydrocephalus (NPH) and brain atrophy is difficult in clinical practice. The purpose of this paper was to apply two advanced statistical, pattern recognition methods: discriminant analysis (DA) and k-nearest neighbour (K-NN) for the classification of NPH and atrophy patients to approach computer aided differential diagnosis. The classification is based on a few measures of the center of foot pressure (COP) movements (radius, area, and length). The posturography method gives a measure of current postural stability by a quantitative evaluation of postural sways. Measurements have been performed in the standing upright position in two conditions: with eyes open (EO) and closed (EC). The study comprises 18 patients (mean age 64 ±13 years) diagnosed as normal pressure hydrocephalus and qualifying for shunt implantation. The patients were evaluated by static posturography twice: before and after surgery. The NPH patients were compared with 36 atrophy patients (mean age 64±13 years) and 47 healthy persons (mean age 60 ±7 years). There were two basic dissimilarities in the NPH patients before surgery in comparison with the other groups: very large sways and their independence from vision. Over 90% of the NPH cases both before and after surgery were correctly classified. There also were over 90% of correctly classified patients if we compared the before surgery NPH and atrophy patients. Further posturographic measurements and data collection are needed to verify these results.

Familial normal pressure hydrocephalus (NPH) with an autosomal-dominant inheritance: a novel subgroup of NPH.

Normal pressure hydrocephalus (NPH) has two clinical forms: secondary NPH and idiopathic NPH (iNPH). Most patients with NPH occur sporadically: until now, only two families have been reported to have sibling cases of NPH. We here report a large family with 4 patients with elderly-onset NPH in three generations. All of them had cognitive impairment, gait disturbance, and urinary problems, along with normal pressure of cerebrospinal fluid. Their brain MRI showed enlargement of the ventricles and a disproportional narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum, which are the features of iNPH on MRI. The family interview also disclosed additional 4 patients who were suspected as having NPH. The disease seems to be inherited in an autosomal-dominant fashion. No known causes of secondary NPH were found in any of the patients. This is the first report to show a large family with NPH patients in three generations, who had clinical and MRI features indistinguishable from iNPH. This seems to represent a novel subgroup of NPH, familial NPH.

Development of guidelines for idiopathic normal-pressure hydrocephalus: introduction.

OBJECTIVE: There are no currently accepted evidence-based guidelines for the diagnosis and management of the normal-pressure hydrocephalus (NPH) patient. As a result, an independent study group was assembled to address this issue and determine the feasibility of developing standardized guidelines, which would be acceptable in the United States and abroad and would be based on the available scientific evidence. The guidelines were to encompass value of clinical presentation, value of supplementary diagnostic tests, surgical management, and outcome assessment. METHODS: Initially, a series of 10 questions were formulated in the areas of pathophysiology, diagnosis, and treatment to obtain a consensus by panels of experts (see Acknowledgments) assembled in San Antonio, TX, in September 2000. This workshop provided significant insight into the difficulties in developing NPH guidelines, and a consensus was reached as to those questions involving expert opinion. Subsequently, evidentiary tables were developed on the basis of the available evidence. Only those studies with 20 or more idiopathic NPH (INPH) patients were included. RESULTS: Sensitivity, specificity, and positive and negative predictive values for INPH diagnostic criteria were assessed, and guidelines were developed on the basis of the available evidence. Recommendations for classification of INPH and additional studies were documented. CONCLUSION: The development of the guidelines was made difficult because systematic studies of INPH and patient numbers were few. It was decided to maintain the classification of NPH into two major categories, INPH and those of known cause (secondary NPH). Many studies "mixed" these classifications, and as a result, they could not be used in the evidentiary tables. Despite these problems, evidence-based guidelines were developed, and it is hoped that they will be useful in guiding clinical management of the INPH patient.

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.

Hidrocefalia de presion normal / Normal pressure hydrocephalus: a reversible dementia

La hidrocefalia de presión normal es una variedad obstructiva pero comunicante de hidrocefalia que cursa con demencia reversible. Su prevalencia se estima entre 1 a 6 por ciento de todas las demencias. Aproximadamente 0.41 por ciento en personas mayores de 65 años. El mayor número corresponde a la etiología idiopática. Otras causas incluyen hemorragia subaracnoidea, trauma craneoencefálico y enfermedades inflamatorias y neoplásicas. La triada sintomática clásica describe trastorno motor, demencia e incontinencia. El diagnóstico se basa en la clínica, las imágenes escanográficas y la resonancia nuclear magnética encefálicas. Se describe el tratamiento quirúrgico (derivación) y los factores predictores de buena respuesta

[Clinical experience with various shunt systems in normal pressure hydrocephalus]. / Klinische Erfahrungen mit verschiedenen Shuntsystemen beim Normaldruckhydrozephalus.

In patients with normal pressure hydrocephalus in the late stage conventional differential valves have the disadvantage that they open abruptly while changing the body position to the vertical line and that they can therefore induce a suction on the ventricles of the atrophic brain. Can these disadvantages and overdrainage complications be minimized by hydrostatic valves? In 117 patients diagnosed for normal pressure hydrocephalus we have implanted 47 Cordis Standard Valves (CSV), 20 Cordis Orbis Sigma Valves Type I (OSV) and 50 Miethke Dual Switch Valves (DSV). 95 patients (36/19/40) could be re-evaluated by means of a control examination. Normal pressure hydrocephalus was graduated according to the results of the intrathecal infusion test in an early and late stage. According to our NPH-Recovery-Rate and to the clinical grading of normal pressure hydrocephalus by Kiefer and Steudel we compared the post-operative results of each group of patients. There were no statistical differences in mechanical and infectious complications between the different valve types. We found significant differences in overdrainage and subdural hematomas. 4 patients (11%) with a CSV, 5 patients (26%) with an OSV and 2 patients (5%) with a DSV had a decrease of the ventricular width visualised in the CT. Of those patients 2 (6%) with a CSV, 3 patients (16%) with an OSV and 1 patient (3%) with a DSV developed clinical symptoms. The course of the disease in patients with normal pressure hydrocephalus is influenced by the stage of the disease--degree of cerebral atrophy--and also by the implanted valve type. The high amount of overdrainage complications and subdural hematomas in the Cordis Orbis Sigma Valve Type I group is an argument against its use. Our clinical experiences with the Miethke Dual Switch Valve show that this hydrostatic valve is of advantage for patients with a normal pressure hydrocephalus.

Acute phase reactant alpha 1-antichymotrypsin is increased in cerebrospinal fluid and serum of patients with probable Alzheimer disease.

Levels of alpha 1-antichymotrypsin (alpha 1-ACT) in cerebrospinal fluid (CSF) and serum from patients with probable Alzheimer disease (AD) of both early (e-AD) and late (l-AD) onset assessed by a competitive enzyme-linked immunosorbent assay were higher than those found in controls or in patients with vascular dementia (VD). A negative correlation between CSF levels of alpha 1-ACT and the stage of the disease was present in patients with both e-AD and l-AD. No difference in alpha 2-macroglobulin levels in CSF and serum from patients with e-AD, l-AD, VD, and nondemented controls was found. Serum concentrations of alpha 1-antitrypsin from l-AD subjects were within the normal range. Thus, increased levels of alpha 1-ACT in CSF and serum were specifically associated with AD, and the detection of this serpin in CSF may be useful in monitoring the progression of the disease.