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PubMed1982

The clinical effect of lumbar puncture in normal pressure hydrocephalus.

Owing to all the difficulties involved in selecting patients with normal pressure hydrocephalus for shunt-operation, a cerebrospinal fluid-tap-test (CSF-TT) is introduced. Psychometric and motor capacities of the patients are measured before and after lumbar puncture and removal of 40-50 ml CSF. Patients fulfilling criteria for normal pressure hydrocephalus were compared to patients with dementia and atrophy shown by computed tomography. Normal pressure hydrocephalus patients showed temporary improvement after lumbar puncture. The extent of the temporary improvement appeared to be well correlated with the improvement after shunt operation. Accordingly, the CSF-TT seems to be of value when selecting those patients who will probably benefit from a shunt operation.

Adult↗
PubMed1979

Intracranial pressure and conductance to outflow of cerebrospinal fluid in normal-pressure hydrocephalus.

Forty patients with clinical evidence of normal-pressure hydrocephalus were studied by monitoring intraventricular pressure during a 24-hour period, and by a lumboventricular perfusion test for measurement of the conductance to outflow of cerebrospinal fluid (CSF). The purpose of the study was to investigate whether there is a relationship between intraventricular pressure and conductance to outflow of CSF, and whether it is possible to use the results from pressure monitoring in the selection of patients who may be expected to benefit from shunting therapy. The conductance to outflow was used as an evaluation factor in the selection of patients to be treated by a shunt. The conductance to CSF outflow differed by twelvefold between the lowest and highest values. The level of resting intraventricular pressure was within normal limits in all patients. Accordingly, there was no evidence of a relationship between conductance to outflow and intraventricular pressure. So-called B-waves were seen more frequently in patients with decreased conductance to outflow, but were also present in patients with high conductance to outflow. Therefore, the presence of B-waves does not imply a low conductance to outflow of CSF.

Adult↗
PubMed1999

Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

Aged↗
PubMed1999

Normal pressure hydrocephalus: developments in determining surgical prognosis.

Research into normal pressure hydrocephalus has often focused on the clinical dilemma of selecting patients who will benefit from cerebrospinal fluid diversion. Recent developments in imaging and lumbar infusion tests are throwing light on the underlying pathophysiology, providing researchers with new avenues for the development of reliable investigative tools.

Humans↗
PubMed2005

The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus.

OBJECTIVE: The diagnosis and management of idiopathic normal-pressure hydrocephalus (INPH) remains unclear. Moreover, the value of supplementary tests to predict which patients would benefit from placement of a shunt has not been established. This report develops evidence-based guidelines for the use of supplementary tests as an aid in prognosis. METHODS: MEDLINE searches from 1966 to the present were undertaken by use of the query NPH, normal-pressure hydrocephalus, lumbar drain, CSF [cerebrospinal fluid] tap test, and external CSF drainage in humans. This resulted in 242 articles. To provide a scientific, evidence-based review, we have chosen to restrict our analysis to clinically relevant studies usually consisting of large numbers of shunted NPH patients. Studies that did not specify INPH or secondary NPH were considered in a separate evidentiary table. RESULTS: Evidence-based guidelines for use in supplementary tests have been developed. A positive response to a 40- to 50-ml tap test has a higher degree of certainty for a favorable response to shunt placement than can be obtained by clinical examination. However, the tap test cannot be used as an exclusionary test because of its low sensitivity (26-61%). Determination of the CSF outflow resistance via an infusion test carries a higher sensitivity (57-100%) compared with the tap test and a similar positive predictive value of 75 to 92%. Prolonged external lumbar drainage in excess of 300 ml is associated with high sensitivity (50-100%) and high positive predictive value (80-100%). CONCLUSION: To date, a single standard for the prognostic evaluation of INPH patients is lacking. However, supplemental tests can increase predictive accuracy for prognosis to greater than 90%. Additional multicenter prospective randomized clinical trials are needed.

Cerebrospinal Fluid Shunts↗
PubMed2004

Linear deposition of immunoglobulins and complement components on the dura in normal pressure hydrocephalus complicating systemic lupus erythematosus.

We present a case of normal pressure hydrocephalus in a 70-year-old man with previously diagnosed systemic lupus erythematosus. Histological examination demonstrated the linear deposition of IgG, IgA, IgM, C(3) and C(1q) on the dura in the absence of inflammation or thrombosis that has previously been implicated in the aetiology of elevated pressure hydrocephalus in systemic lupus erythematosus. Our results suggest that the deposition of immunoglobulins and complement may play a pivotal role in an insidious manner in the pathogenesis of normal pressure hydrocephalus in systemic lupus erythematosus.

Aged↗
PubMed1991

Binswanger's disease and normal-pressure hydrocephalus. Clinical and neuropsychological comparison.

We investigated the clinical and cognitive aspects of patients with normal-pressure hydrocephalus and possible Binswanger's disease. We studied 19 patients with normal-pressure hydrocephalus and 19 patients with Binswanger's disease, comparing them with the same number of matched controls. The patients with normal-pressure hydrocephalus had a later age and more frequent gait disturbance at the onset, shorter duration of the illness, rare signs of vascular disturbances, and more frequent severe mental deterioration. Ventricular enlargement may play a role in determining the more rapid and worse clinical course of normal-pressure hydrocephalus.

Aged↗
PubMed1987

Idiopathic normal pressure hydrocephalus and systemic hypertension.

Nineteen patients with idiopathic normal pressure hydrocephalus (NPH) were treated with intraventricular shunts. Ten of the 14 who improved and 14 of the total group had systemic hypertension. The prevalence of hypertension in both the improved and whole NPH groups was significantly greater than in a control group with dementia (N = 122) and the published prevalence of hypertension in the US population for this age group. Four possible mechanisms for this association are discussed.

Aged↗
PubMed1992

Normal pressure hydrocephalus. A potentially reversible form of dementia.

1. Normal pressure hydrocephalus (NPH) is a rare but potentially treatable form of dementia. Shunting will improve functioning in 40% to 50% of patients. 2. The classic symptoms of NPH are dementia characterized by mild memory impairment and apathy, ataxic gait, and urinary hesitancy or incontinence. 3. The patient with NPH may present with psychiatric symptoms of depression, paranoia, visual hallucinations, irrational hostility, and aggression or mania. 4. Patients with NPH are indifferent about activities of daily living and personal safety and require close supervision.

Aged↗
PubMed1982

Cerebrospinal fluid proteins and cells in normal-pressure hydrocephalus.

A total of 21 patients with normal-pressure hydrocephalus were examined. Cerebrospinal fluid (CSF) was collected before and after operation with a ventriculoperitoneal shunt. A slight plasma-like protein pattern indicating a blood-brain barrier (BBB) dysfunction was seen in 38% of the patients before operation. No characteristic changes could be found in the "CSF-specific" protein fraction. After the shunt operation 65% of the patients had a BBB dysfunction to macromolecules and 70% had two additional acidic protein bands in the CSF-specific fraction. Ventricular CSF protein content was 73% of lumbar CSF content when shunts were patent. Isotope encephalography showed a radionuclide accumulation at the intracranial part of the shunt system, indicating that the BBB damage might be located round the shunt catheter.

Blood-Brain Barrier↗
PubMed1997

Psychiatric manifestations of normal-pressure hydrocephalus: a short review and unusual case.

Normal-pressure hydrocephalus (NPH) is a common cause of potentially reversible dementia. It can present with psychiatric manifestations that may hinder its diagnosis. A 68-year-old man presented with a paranoid psychosis and mild cognitive impairment, but not neurological signs or classic "triad." Gait disturbance and urinary incontinence developed later in the course of illness after the diagnosis of NPH had already been made on computed tomographic (CT) scanning. A lumbo-peritoneal shunt was performed, followed by full remission of psychotic symptoms, as well as considerable improvement in functioning, continence, and gait. This case demonstrates the need to consider NPH when older patients present with psychotic symptoms, particularly in the presence of cognitive impairment, gait disturbance, or incontinence. The decision whether to perform a shunting operation is often difficult, because selection of patients with good prognosis is still inaccurate. CT scanning of the brain is an important investigation in older patients presenting with both functional and organic disorders.

Aged↗
PubMed2006

Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics.

BACKGROUND: The pathogenesis of idiopathic normal pressure hydrocephalus (INPH) is unknown, and the syndrome of INPH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis and treatment of INPH and thus to study their role in the disease process. METHODS: A comparative proteomic analysis was used for clinical screening of cerebrospinal fluid (CSF) proteins in 15 patients with INPH and compared with 12 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with CSF proteins between individual INPH patients and controls. RESULTS: Seven proteins and their isoforms, including leucine-rich alpha-2-glycoprotein (LRG), alpha1-antichymotrypsin, apolipoprotein D, apolipoprotein J, haptoglobin alpha1, serum albumin, and alpha-1-microglobulin/bikunin precursor showed significant changes in CSF of INPH patients compared with controls by proteomic analysis. And significant higher CSF levels of LRG in INPH patients compared with controls were found by ELISA. CONCLUSIONS: These results indicate that there are significant differences in the expression of certain proteins in the CSF of patients with INPH and normal subjects. In particular, the CSF level assay of LRG suggests that LRG is a specific biomarker for INPH and has potential use in the diagnosis and indication for CSF shunting.

Aged↗
PubMed1992

[Changes in dementia after shunt surgery for normal pressure hydrocephalus].

In order to investigate the pathogenesis of normal pressure hydrocephalus (NPH), dementia was analyzed with regard to the characteristic preoperative picture, the time when dementia improved, and what aspect of dementia was improved, retrospectively. Twenty seven patients of NPH were divided into two groups; young adult group: patients under 64 years old and geriatric group: patients above 65 years old. We found that the only difference found between these two groups was severity in dementia grading, higher in geriatric group. Postoperative course or complications did not differ. Dementia in NPH was not an essential impairment of intellectual ability, but was characterized by the subset symptoms of dementia, such as decrease in spontaneity and interest, slowness and paucity of thought and action. Improvement of memory followed postoperative recovery of these subset symptoms which was observed at earliest three days after shunt surgery. We postulate that recovery of dementia in NPH is associated with not only a decrease in intracranial pressure but also an improvement in the microcirculation of the brain or an improved metabolism.

Adult↗
PubMed2002

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.

Atrophy↗
PubMed2006

In vivo presynaptic and postsynaptic striatal dopamine functions in idiopathic normal pressure hydrocephalus.

Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the trans-synaptic dopamine functions in the striatal region in eight iNPH patients naïve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens (P<0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity (r=0.720, P<0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score (r=0.727, P<0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.

Aged↗
PubMed2003

Normal pressure hydrocephalus triggers intrathecal production of TNF-alpha.

Normal pressure hydrocephalus (NPH) is associated with periventricular white matter lesions and demyelination. The aim of the present study was to examine the cerebrospinal fluid (CSF) levels of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine mediating myelin damage, in patients with NPH. TNF-alpha levels were analyzed by ELISA and measured before and after shunt operation in 35 patients with NPH. The levels of this cytokine were related to the symptomatology and to magnetic resonance imaging (MRI) verified white matter lesions. They were also related to intrathecal levels of sulfatide, a marker for white matter degradation and to levels of neurofilament, a marker for neuronal degeneration. The preoperative levels of TNF-alpha were increased in the CSF of NPH patients compared to controls, and correlated to the levels of sulfatide. The intrathecal TNF-alpha levels were higher in NPH patients with impairment of wakefulness than in those without this symptom. The preoperative TNF-alpha levels were significantly correlated to the improvement of psychometrical test scores, and of wakefulness and to the overall improvement of the patients following shunt operation. Importantly, shunt operation led to complete disappearance of intrathecal TNF-alpha. We conclude that NPH is correlated with intrathecal TNF-alpha production being reversed following shunt operation in parallel with the clinical improvement. The positive correlation between preoperative TNF-alpha and sulfatide levels in the CSF suggest that intrathecal TNF-alpha may contribute to the damage of the white matter known to occur in patients with NPH.

Adult↗