The Dutch normal-pressure hydrocephalus study. How to select patients for shunting? An analysis of four diagnostic criteria.

BACKGROUND: Comparison of the predictive value of four "diagnostic tests" for the outcome of shunting in patients with normal-pressure hydrocephalus (NPH). METHODS: Ninety-five NPH patients who received shunts were followed for 1 year. Gait disturbance and dementia were quantified by an NPH scale and handicap by a modified Rankin scale. Primary outcome measures were differences between the preoperative and last scores on both the NPH scale and the modified Rankin scale. Clinical and computed tomographic (CT) findings typical of NPH, absence of cerebrovascular disease, and a resistance to outflow of cerebrospinal fluid (CSF) >/= 18 mmHg/ml/minute were designated as a positive test outcome; clinical and CT findings compatible with NPH, presence of cerebrovascular disease, and an outflow resistance < 18 mmHg/ml/minute as a negative test outcome. RESULTS: For each of the four tests the percentage of patients classified as improved was significantly greater for those with positive than with negative test results. Measurement of CSF outflow resistance was the only significant prognostic factor for the improvement ratio in NPH scale and CT in the modified Rankin scale according to multivariate logistic regression analysis. The accurate predictive value of the combination of typical clinical and CT findings was 0.65, that of the positive test results of outflow resistance, clinical and CT findings was 0.74. CONCLUSION: The best strategy is to shunt NPH patients if their outflow resistance is >/= 18 mmHg/ml/minute or, when the outflow resistance is lower, if their clinical as well as their CT findings are typical of NPH.

Cystic lesions accompanying extra-axial tumours.

We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural schwannomas. Measuring concentrations of various proteins [albumin, immunoglobulin G (IgG), IgA, alpha 2-macroglobulin and IgM] in cyst fluid, CSF and blood plasma provides insight into the state of the semipermeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier. Peritumoral cysts accompanying intra-axial brain tumours are the end result of disruption of the BBB and oedema formation. Unlike intra-axial tumours which lie embedded within nervous tissue, extra-axial tumours tend to be separated from nervous tissue by arachnoid and pia mater. High concentrations of proteins were measured in the cyst fluid, approaching blood plasma levels, suggesting a local barrier disruption, and passage across the arachnoid, pia mater and cortical/medullary layer into the CNS parenchyma, leaving the protein concentrations of CSF practically unchanged. We confirmed that very high concentrations of protein are to be found in tumour cysts, plasma proteins forming almost 90% of the total protein in the cyst. We review current hypotheses on the pathogenesis of cysts accompanying neoplasms, particularly meningiomas and schwannomas, and conclude that the majority of proteins in cyst fluid in extra-axial, intradural meningiomas and schwannomas are plasma proteins. This provides a strong argument for pathogenesis of extra-axial intradural tumour cysts in favour of leakage of plasma proteins out of the tumour vessels into the nervous tissue.

Dutch Normal-Pressure Hydrocephalus Study: the role of cerebrovascular disease.

OBJECT: This study was conducted to determine the prevalence of cerebrovascular disease and its risk factors among patients with normal-pressure hydrocephalus (NPH) and to assess the influence of these factors on the outcome of shunt placement. METHODS: A cohort of 101 patients with NPH underwent shunt placement and was followed for 1 year. Gait disturbance and dementia were quantified using an NPH scale and handicap was determined using a modified Rankin scale (mRS). Primary outcome measures consisted of the differences between preoperative and last NPH scale and mRS scores. The presence of risk factors such as hypertension, diabetes mellitus, cardiac disease, peripheral vascular disease, male gender, and advancing age was recorded. Cerebrovascular disease was defined as a history of stroke or a computerized tomography (CT) scan revealing infarcts or moderate-to-severe white matter hypodense lesions. The prevalence of risk factors for cerebrovascular disease was higher in the 45 patients with cerebrovascular disease than the 56 without it. Risk factors did not influence outcome after shunt placement. Intent-to-treat analysis revealed that the mean improvement in the various scales was significantly less for patients with a history of stroke (14 patients), CT scans revealing infarctions (13), or white matter hypodense lesions (32 patients) than for those without cerebrovascular disease. The proportion of patients who responded to shunt placement was also significantly lower among patients with than those without cerebrovascular disease (p=0.02). CONCLUSIONS: The authors identified a subgroup of patients with NPH and cerebrovascular disease who showed disappointing results after shunt placement. Cerebrovascular disease was an important predictor of poor outcome.

Analysis of fluid in cysts accompanying various primary and metastatic brain tumours: proteins, lactate and pH.

There is a growing interest in cystic lesions of the brain. By examining the cyst content of brain tumours more insight into the pathogenesis of cyst formation has been found. In this study, 39 samples of cyst fluid of 34 patients with a cyst accompanying a brain tumour were collected and studied biochemically regarding their protein content, lactate and pH. In this study we investigated the relation between the grade of malignancy and the lactate-concentration and the discrepancy between the high levels of lactate in cysts and their alkaline environment. The results of the measurements of the concentrations of albumin, immunoglobulines (IgG, IgA, IgM) and alpha 2-macroglobulin in cysts compared to those in sera suggest that cyst formation associated with tumour is based upon a disruption of the blood-brain barrier with exudation of plasma proteins into the brain parenchyma resulting in accumulation of fluid (oedema) and eventually in formation of a cyst. There appears to be a positive relation between the grade of malignancy and the concentration of lactate in the cysts with a significant 2-fold increase in lactate concentration in malignant tumour cysts compared to the more benign tumour cysts (p < 0.001) probably on account of aerobic glycolysis with production of lactate by the tumour. The measured pH values in the cysts were above normal, resulting in a discrepancy of the high levels of lactate in the cyst with the alkaline environment and this suggests efflux of H(+)-ions by a Na/H exchange mechanism to compensate for the change of pH.

Dutch Normal-Pressure Hydrocephalus Study: randomized comparison of low- and medium-pressure shunts.

OBJECT: The goal of this prospective study was to compare outcome after placement of a low- or medium-pressure shunt in patients with normal-pressure hydrocephalus (NPH). METHODS: Ninety-six patients with NPH were randomized to receive a low-pressure ventriculoperitoneal shunt (LPV; 40 +/- 10 mm H2O) or medium high-pressure ventriculoperitoneal shunt (MPV; 100 +/- 10 mm H2O). The patients' gait disturbance and dementia were quantified by applying an NPH scale, and their level of disability was evaluated by using the modified Rankin scale (mRS). Patients were examined prior to and 1, 3, 6, 9, and 12 months after surgery. Primary outcome measures were determined by differences between preoperative and last NPH scale scores and mRS grades. The LPV and MPV shunt groups were compared by calculating both the differences between mean improvements and the proportions of patients showing improvement. Intention-to-treat analysis of mRS grades yielded a mean improvement of 1.27 +/- 1.41 for patients with LPV shunts and 0.68 +/- 1.58 for patients with MPV shunts (p = 0.06). Improvement was found in 74% of patients with LPV shunts and in 53% of patients with MPV shunts (p = 0.06) and a marked-to-excellent improvement in 45% of patients with LPV shunts and 28% of patients with MPV shunts (p = 0.12). All outcome measures indicated trends in favor of the LPV shunt group, with only the dementia scale reaching significance. After exclusion of serious events and deaths unrelated to NPH, efficacy analysis showed the advantage of LPV shunts to be diminished. Reduction in ventricular size was also significantly greater for patients in the LPV shunt group (p = 0.009). Subdural effusions occurred in 71% of patients with an LPV shunt and in 34% with an MPV shunt; however, their influence on patient outcome was limited. CONCLUSIONS: Outcome was better for patients who had an LPV shunt than for those with an MPV shunt, although most differences were not statistically significant. The authors advise that patients with NPH be treated with an LPV shunt.

The pathogenesis of cysts accompanying intra-axial primary and metastatic tumors of the central nervous system.

Recent reports have suggested that cyst formation accompanying astrocytomas in the central nervous system (CNS) is due to an edematous process caused by blood-brain barrier (BBB) disruption and not a result of necrosis. This study is performed to investigate whether the hypothesis of cyst formation based on BBB disruption also applies to various pathologically different intra-axial gliomatous tumors and metastases. By chemical analysis, using immunokinetic nephelometry, isoelectric focussing, cellulose acetate electrophoresis and a biuretic method, the concentrations of albumin, immunoglobulin G (IgG), IgA, alpha2-macroglobulin, IgM and total protein were measured and proportions of concentrations of these proteins were compared in cyst fluid, blood plasma and cerebrospinal fluid (CSF). Our data, based on the chemical analysis of cyst fluid and blood plasma of 37 patients, including 2 ependymomas (one cerebral; one thoracic), 3 oligodendrogliomas, 4 hemangioblastomas, 5 cerebellar astrocytomas and 1 cervical, 1 giant astrocytoma grade one, 1 gangliocytoma, 1 neuroblastoma and 19 metastases (five lung-; two renal-; three breast-; one melanoma-; one thyroid metastasis and seven metastases of unknown origin) present high protein concentrations in the cysts with a highly similar spectrum of proteins in the tumor cyst fluid and blood plasma, suggesting a BBB disruption followed by exudation of plasma proteins into the brain parenchyma with formation of edema and transition of edematous tissue into a cyst accompanying the tumor. Although histopathologically different types of tumor tissue are involved, data suggests that the pathogenesis of cysts accompanying gliomatous tumors and metastases in the CNS is based on BBB disruption and consequent edema, as is the case in the formation of cysts in anaplastic astrocytomas.

Dutch normal-pressure hydrocephalus study: prediction of outcome after shunting by resistance to outflow of cerebrospinal fluid.

The authors examined whether measurement of resistance to outflow of cerebrospinal fluid (Rcsf) predicts outcome after shunting for patients with normal-pressure hydrocephalus (NPH). In four centers 101 patients (most of whom had idiopathic NPH) who fulfilled strict entry criteria underwent shunt placement irrespective of their level of Rcsf obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified by using an NPH scale and the patient's level of disability was assessed by using the modified Rankin scale (mRS). In addition the Modified Mini-Mental State Examination was performed. Patients were assessed prior to and 1, 3, 6, 9, and 12 months after surgery. Primary outcome measures were based on differences between the preoperative and last NPH scale scores and mRS grades. Improvement was defined as a change measuring at least 15% in the NPH scale score and at least one mRS grade. Intention-to-treat analysis of all patients at 1 year yielded improvement for 57% in NPH scale score and 59% in mRS grade. Efficacy analysis, excluding serious events and deaths that were unrelated to NPH, was performed for 95 patients. Improvement rose to 76% in NPH scale score and 69% in mRS grade. Six cut-off levels of Rcsf were related to improvement in NPH scale score using two-by-two tables. Positive predictive values were approximately 80% for an Rcsf of 10, 12, or 15 mm Hg/ml/minute, 92% for an Rcsf of 18 mm Hg/ml/minute, and 100% for an Rcsf of 24 mm Hg/ml/minute. Negative predictive values were low. More important was the highest likelihood ratio of 3.5 for an Rcsf of 18 mm Hg/ml/minute. Extensive comorbidity was a major prognostic factor. Measurement of Rcsf reliably predicts outcome if the limit for shunting is raised to 18 mm Hg/ml/minute. At lower Rcsf values the decision depends mainly on the extent to which clinical and computerized tomography findings are typical of NPH.

The pathogenesis of syringomyelia in spinal cord ependymoma.

A spinal cord ependymoma with syringomyelia is presented. The pathogenesis of syrinx formation, associated with intramedullary tumors is not fully understood. In order to examine the mechanism of formation of the tumor-associated syrinx, syrinx fluid was obtained during surgery and concentrations of proteins were measured in the syrinx fluid, the cerebrospinal fluid (CSF) and blood serum. Protein analysis of fluid specimens showed the fluid in tumor-associated syrinx to be an exudate. This strongly indicates that, in this case, intramedullary tumor-associated syringomyelia is based on disruption of the blood-brain barrier.