Biomedical subjects

C J Avezaat

Publications and source records attributed to C J Avezaat.

At least 19 recordsLinked to original sources

PubMed2001

Treatment of malignant gliomas with a replicating adenoviral vector expressing herpes simplex virus-thymidine kinase.

We evaluated the interaction between oncolytic, replication-competent adenoviral vectors and the herpes simplex virus-1 thymidine kinase (HSV1-tk) gene/ganciclovir (GCV) suicide system for the treatment of malignant gliomas. We constructed a panel of replication-competent adenoviral vectors in which the luciferase (IG.Ad5E1(+). E3Luc) or HSV1-tk gene (IG.Ad5E1(+).E3TK) replace the M(r) 19,000 glycoprotein (gp19K) coding sequence in the E3 region. IG.Ad5E1. IG.Ad5.ClipLuc and IG.AdApt.TK are E1-deleted viruses that contain the luciferase or the HSV1-tk gene in the former E1 region driven by the human cytomegalovirus promoter. IG.Ad5. Sarcoma 1800HSA.E3Luc contains an irrelevant gene in the E1 region, whereas the gp19K coding sequence in the E3 region is replaced by the luciferase gene as in the replicating virus IG.Ad5E1(+).E3Luc. For in vitro experiments, we used a panel of human glioma cell lines (U87 MG, T98G, A172, LW5, and U251), a rat gliosarcoma cell line (9 L), and human lung (A549) and prostate carcinoma (P3) cell lines. In vitro, GCV sensitivity (10 microg/ml) was studied in U87 MG cells after infection at a multiplicity of infection of 1 and 10. A s.c. U87 MG glioma xenograft model was established in NIH-bg-nu-xid mice. Tumors of 100-150 mm(3) were treated with a single injection of adenovirus 10(9) IU suspended in 100 microl of PBS, and GCV 100 mg/kg was administered i.p. twice daily for 7 days. The cytopathic effect of all three replication-competent adenoviral vectors was similar to the cytopathic effect of wild-type adenovirus 5 on all human cell lines tested, indicating that deletion of the E3 gp19K sequences did not affect the oncolytic effect of the vectors. In vitro, luciferase expression was the same for both E1-deleted vectors (IG.Ad5.ClipLuc and IG.Ad5. Sarcoma 1800HSA.E3Luc), demonstrating the strength of the internal E3 promoter even in the absence of E1A. However, in vitro expression levels obtained with replication-competent IG.Ad5E1(+). E3Luc were 3 log higher (allowing infection with a 2-3-log lower multiplicity of infection) in the human cell lines. In U87 MG glioma cells, the oncolytic effect of replication-competent IG.Ad5E1(+).E3TK was significantly enhanced by the addition of GCV and greatly exceeded the cytotoxicity of replication-incompetent IG.AdApt.TK combined with GCV. In established s.c. U87 MG glioma xenografts, a single injection of IG.Ad5E1(+).E3TK resulted in a significant slowing of tumor growth and prolonged survival compared with injection of IG.AdApt.TK. Addition of GCV slowed tumor growth, further adding to survival. In conclusion, the oncolytic effect of replicating adenoviral vectors and HSV1-tk/GCV have potent antitumor effects in gliomas. When combined, these two approaches are complementary, resulting in a significantly improved treatment outcome. In addition, replication-competent adenoviral vectors missing the E3 gp19K coding sequences, have oncolytic efficacy comparable with wild type. In combination with high expression levels obtained with the natural E3 promoter, such vectors are promising new anticancer agents.

Adenoviridae↗

PubMed2001

['Benign' meningioma].

Meningioma was diagnosed in four women, aged 40, 24, 41 and almost 75 years, respectively. The first of these patients was treated with surgery, the second and third patients underwent surgery followed by conventional radiotherapy because of a tumour residue or dural tail, and the last patient was treated with stereotactic radiosurgery. They recovered well and were followed by means of regular outpatient check-ups. Twenty percent of all primary brain tumours are meningiomas, over 90% of which are benign. Nevertheless, a large hospital-based population study showed a 5-year survival rate of only 70%. Microsurgery is usually the treatment of first choice. However, in about 25% of cases, excision is incomplete and tumour growth almost always continues. Further surgery influences prognosis unfavourably. New sophisticated radiation techniques help to control tumour progression in about 80-90% of cases. This success, however, may be associated with new cranial nerve deficits or panhypopituitarism. Prospective, comparative studies are not available.

Adult↗

PubMed2001

Spatial variability of genomic aberrations in a large glioblastoma resection specimen.

In the present study, the distribution of genetic aberrations in a glioblastoma resection specimen of unusually large size (9x8x2 cm) was investigated using comparative genomic hybridization (CGH). CGH was performed on 20 samples taken from the specimen, and the genetic aberrations found were compared with the regional histology. The samples were histopathologically graded according to WHO criteria, and a division in high- and low-grade areas and infiltration rims was made. In high-grade areas, low-grade areas as well as infiltration rims, gains on 10p11.2-pter (14/20), 11q12-q22 (6/20) and losses on 4q13-qter (9/20), 10q22-qter (8/20), 11p14-pter (5/20), 13q12-qter (7/20) were revealed. Gains on 1q21-32 (2/4) and losses on 7p21-pter (3/4) were exclusively found in the high-grade areas. In the low-grade tumor samples and in the infiltration rim, gains on 16p11.2-pter (6/16), 17p11.2-pter (6/16), 17q11.2-qter (5/16), 20q11.2-q13 (3/16) and deletions on 5q31-qter (4/16) were detected. Gains on 7q21-qter (8/11) and 8q11.2-qter (6/11), and loss of chromosome 9 (4/11) and the Y-chromosome (4/11) were found in the high-grade and low-grade samples, not in the infiltration rims. The finding of a set of identical chromosomal aberrations throughout the resection specimen, most of which have been previously reported in gliomas, confirms a mechanism of clonal tumor proliferation operative in gliomas. The previously unreported genetic alterations which were predominantly traced in the tumor rims, might reflect either selection for properties related to infiltrating behavior, or genomic instability of subclones. The findings illustrate the importance of searching for high-grade genetic aberrations in low-grade tumor samples taken from cases in which sampling error is suspected.

Brain Neoplasms↗

PubMed2001

Analysis of hearing loss after shunt placement in patients with normal-pressure hydrocephalus.

OBJECT: Following shunt placement for treatment of normal-pressure hydrocephalus (NPH), several patients suffered hearing loss. The authors undertook a study to analyze this outcome. METHODS: Sixteen patients in whom NPH was diagnosed were treated by placement of a ventriculoperitoneal shunt. Their hearing was assessed pre- and postoperatively by using pure tone audiometry. Two thirds of the ears tested showed a postoperative hearing loss of more than 10 dB. Recovery of the hearing loss occurred 6 to 12 weeks after shunt placement in 75% of the ears examined. CONCLUSIONS: Although shunt insertion for treatment of NPH results in a decrease in hearing, most of the loss can be recovered.

Aged↗

PubMed2000

Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels.

BACKGROUND: Eletriptan is a 5-HT(1B/1D) receptor agonist with proven efficacy in the acute treatment of migraine. OBJECTIVE: To assess the craniovascular selectivity of eletriptan and sumatriptan in blood vessels predictive of therapeutic efficacy (human middle meningeal artery) and adverse coronary side effects (human coronary artery and human saphenous vein). METHOD: The authors obtained coronary artery from organ donors (n = 9), middle meningeal artery from patients (n = 11) undergoing craniotomy, and saphenous vein from patients (n = 9) undergoing coronary bypass surgery. Concentration-response curves to eletriptan and sumatriptan were constructed to obtain measurements of efficacy (maximum contraction, E(max)) and potency (concentration eliciting 50% of E(max), EC(50)). The contraction that is likely to be induced at the maximal free plasma concentration (C(max)) was determined by calculating C(max)/EC(50) ratios and by interpolation of the concentration-response curves. RESULTS: Eletriptan and sumatriptan induced concentration-dependent contractions of meningeal artery, coronary artery, and saphenous vein. Eletriptan was less potent than sumatriptan in coronary artery, whereas both compounds had similar potency in meningeal artery and saphenous vein. However, the potency of eletriptan and sumatriptan was higher in meningeal artery than in coronary artery (86-fold for eletriptan and 30-fold for sumatriptan) or saphenous vein (66- and 25-fold). The efficacy of eletriptan and sumatriptan was similar within tissues. The predicted contraction by eletriptan (40 mg and 80 mg) and sumatriptan (100 mg) at free C(max) observed in clinical trials was similar in meningeal artery, whereas in coronary artery and saphenous vein it was lower for 40 mg eletriptan than for sumatriptan. CONCLUSIONS: At therapeutic concentrations both eletriptan and sumatriptan contract middle meningeal artery more than coronary artery. This suggests that in patients with healthy coronary arteries, they have a limited propensity to cause adverse coronary side effects. However, both drugs remain contraindicated in patients with coronary artery disease.

Aged↗

PubMed2000

Pharmacological analysis of contractile effects of eletriptan and sumatriptan on human isolated blood vessels.

Eletriptan, a second-generation triptan with high affinity for 5-HT(1B/1D) receptors, is highly effective in migraine, with or without aura. We compared the effects of eletriptan and sumatriptan on the human isolated middle meningeal and coronary arteries and saphenous vein, used as models for therapeutic efficacy and potential side effects, and have investigated the role of 5-HT(1B/1D) receptors in contractions induced by these triptans. Concentration-response curves to eletriptan and sumatriptan were constructed in the absence or presence of a selective 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-py rid yl) benzamide (GR125743). All three blood vessels constricted in response to eletriptan and sumatriptan, but the middle meningeal artery relaxed following the highest concentration (100 microM) of eletriptan. In the middle meningeal artery, GR125743 antagonised the contractions induced by both eletriptan (pEC(50): 7.34+/-0.13) and sumatriptan (pEC(50): 6.91+/-0.17) to a similar degree (pA(2): 8. 81+/-0.17 and 8.64+/-0.21, respectively). In the human coronary artery and saphenous vein, sumatriptan-induced contractions (pEC(50): 6.24+/-0.14 and 6.19+/-0.12, respectively) were also potently antagonised by GR125743 (pA(2): 8.18+/-0.27 and 8.34+/-0.12, respectively). The eletriptan-induced contractions of the human saphenous vein (pEC(50): 6.09+/-0.13) were antagonised less effectively by GR125743 (pK(B): 7.73+/-0.18), and those of the human coronary artery (pEC(50): 5.54+/-0.22) remained unaffected by GR125743 up to a concentration of 100 nM. These results suggest that (i) based on the differences in pEC(50) values, the cranioselectivity of eletriptan (63-fold) is higher than that of sumatriptan (5-fold) in coronary artery, (ii) the contractile effects of sumatriptan and eletriptan (lower concentrations) in the three blood vessels are mediated via the 5-HT(1B) receptor, and (iii) additional mechanisms seem to be involved in coronary artery and saphenous vein contractions and middle meningeal artery relaxation following high concentrations of eletriptan.

Adult↗

PubMed2000

Interobserver variability of cisternal blood on CT after aneurysmal subarachnoid hemorrhage.

Interobserver variability in the prediction of delayed cerebral ischemia by means of blood on CT was investigated in 159 patients with aneurysmal subarachnoid hemorrhage, admitted within 72 hours after the bleed. The authors found considerable interobserver variability in the assessment of the amount of blood in the individual cisterns. A high sum score was an independent predictor for delayed cerebral ischemia only for rater 1 (rater 1: hazard ratio, 3.26; 95% confidence interval [CI], 1.14 to 7.75; rater 2: hazard ratio, 1.72; 95% CI, 0.72 to 4.09). The authors conclude that interobserver variability limits the predictive power of the amount of blood on CT for the occurrence of cerebral ischemia.

Brain Ischemia↗

PubMed2000

Hydrostatic and hydrodynamic considerations in shunted normal pressure hydrocephalus.

Symptoms of overdrainage, a frequent complication following shunting procedures especially in patients with normal-pressure hydrocephalus (NPH), are presumed to be caused by siphoning: gravity-enhanced flow of cerebro spinal fluid (CSF) through shunts in upright position. A critical reappraisal of siphoning and overdrainage (OD) is presented considering the occurrence of subdural hygromas (SDH) encountered in a group of patients shunted for NPH. The patients participated in the multicentre Dutch NPH study: 101 NPH patients were randomised for treatment with shunts with low or medium-high working pressure. Treatment with shunts with low working pressure resulted in an increased incidence of SDH (iSDH). Current physiological concepts of overdrainage are discussed and criticised. A new theory is presented on the basis of general physiological considerations. The theoretical model proposed yields a revised explanation for the origin of extremely low ventricular pressure in the upright position found with overdrainage. The efficacy of siphoning-preventing shunts and subtemporal decompression is explored in the light of the proposed theory.

Cerebrospinal Fluid↗

PubMed2000

Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity.

High doses of adenotk were injected into the cerebrospinal fluid of rats and nonhuman primates (Macaca mulatta). Vector administration was followed by ganciclovir administration for 14 days. Despite the absence of clinical symptoms, analysis of the cerebrospinal fluid (CSF) and histopathological examination of the central nervous system (CNS) of the monkeys (3 weeks after vector injection) were consistent with a viral meningitis. Immunohistochemical analysis of the inflammatory infiltrates in the monkeys revealed the presence of T and B lymphocytes, indicating a combined cellular and humoral immune response to the vector. This latter was supported by the finding of intrathecal anti-adenovirus antibody synthesis. Rats receiving high intrathecal adenotk doses showed a transient and dose-dependent clinical toxicity consisting of lethargy, hyperemic eyes and weight loss. Histopathological examination of the meninges showed a shift from polymorphonuclear infiltrates during the first post-injection days to clusters of mononuclear cells after 7 days. Acute toxicity is probably related to the early, innate immune response to the vector. In a separate experiment, high levels of IL-8 and IL-6, were measured during the first 2-3 post-injection days in the CSF of two monkeys which received intrathecal adenoLacZ. Therefore, these cytokines seem to play an important role in initiating the nonspecific immune response. In one monkey which received adenotk, recombinant adenovirus was cultured from serum samples obtained at the 7th post-injection day. At this time-point, no vector could be isolated from CSF samples. Based on these preclinical data, we recommend careful dose finding for clinical studies that aim to treat patients with leptomeningeal metastases.

Adenoviridae↗

PubMed2000

CO2 reactivity and brain oxygen pressure monitoring in severe head injury.

OBJECTIVE: To investigate the effect of hyperventilation on cerebral oxygenation after severe head injury. DESIGN: A prospective, observational study. SETTING: Neurointensive care unit at a university hospital. PATIENTS: A total of 90 patients with severe head injury (Glasgow Coma Scale score < or =8), in whom continuous monitoring of brain tissue oxygen pressure (PbrO2) was performed as a measure of cerebral oxygenation. INTERVENTIONS: Arterial PCO2 was decreased each day over a 5-day period for 15 mins by increasing minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2 reactivity was calculated. Outcome at 6 months was evaluated according to the Glasgow Outcome Scale. MEASUREMENTS AND MAIN RESULTS: Effective hyperventilation, defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%) of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60 kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2 decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day 1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/- 4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2 was not related to outcome. In later phases in patients with unfavorable outcome, relative reactivity was increased more markedly, reaching statistical significance on day 5. CONCLUSIONS: Increased hyperventilation causes a significant reduction in PbrO2, providing further evidence for possible increased risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2 reactivity on day 1 indicates the decreased responsiveness of cerebral microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing. The increasing PbrO2/PaCO2 reactivity from days 2 to 5 suggests that the risk of compromising cerebral oxygenation by hyperventilation may increase over time.

Adolescent↗

PubMed2000

Brain oxygen tension in severe head injury.

OBJECTIVE: Ensuring adequate cerebral oxygenation and perfusion is of fundamental importance in the treatment of patients with acute cerebral disorders. Online continuous monitoring of brain oxygenation is possible with a parenchymal microelectrode that measures local brain oxygen tension. The ultimate question is whether therapeutic approaches can be targeted on the basis of such monitoring. Before this question can be addressed, the technique requires validation in the clinical setting. The frequency of occurrence of low values and its relation to outcome need to be established. METHODS: One hundred one comatose head-injured patients (Glasgow Coma Scale score < or = 8) were studied. Local brain oxygen tension probes were inserted in an undamaged part of the frontal region. Patients were treated in conformance with the European Brain Injury Consortium guidelines. Outcome at 6 months was determined by Glasgow Outcome Scale score. RESULTS: Early brain tissue hypoxia was frequently observed, despite aggressive treatment for intracranial pressure and cerebral perfusion pressure. Values lower than 15 mm Hg, for a duration longer than 30 minutes, were observed in 57 patients. Values lower than 10 mm Hg in 42 patients, and lower than 5 mm Hg in 22 patients, were observed during the first 24 hours. Depth and duration of tissue hypoxia were related to outcome and proved to be an independent predictor of unfavorable outcome and death. CONCLUSION: Monitoring the partial oxygen pressure of local brain tissue is a safe and reliable method for regulating cerebral oxygenation. Because brain tissue hypoxia occurs frequently and is significantly related to poor outcome, future efforts should be aimed at the treatment of brain tissue hypoxia. The effects of such brain hypoxia-targeted treatment need to be established in a multicenter study.

Adolescent↗

PubMed1999

Distribution of recombinant adenovirus in the cerebrospinal fluid of nonhuman primates.

Gene therapy by administration of vectors into the cerebrospinal fluid (CSF) may be used in treatment of leptomeningeal metastases (cancer gene therapy) as well as in treatment of neurodegenerative disorders, traumatic injury, and chronic pain. Recombinant adenoviruses are attractive vectors for intra-CSF administration because they can efficiently transfer genes into the nonreplicating cells of the central nervous system (CNS). In addition, they can be produced in high titers and, because no producers cells are introduced, the risk of CSF obstruction by clustering cells is circumvented. However, successful application requires favorable distribution dynamics, high transduction efficiency, and long-lasting transgene expression. In this study we examined the distribution of a recombinant adenovirus containing the lacZ gene after administration into the CSF of nonhuman primates. After intraventricular and suboccipital administration, homogeneous distribution of the vector along the meninges covering the brain and spinal cord was obtained, as demonstrated by extensive and intense blue staining of cells, predominantly in the arachnoid and pia mater. In one animal we also found beta-galactosidase activity in the cervical paraspinal fat and in one of the deep cervical lymph nodes, indicating drainage of the vector or vector products with CSF into cervical lymph. This route of vector clearance from the CNS may result in antigenic presentation and an effective immune response and may explain the sixfold higher serum antibody titers after intrathecal injection of adenovirus as compared with intranasal application in Fischer rats. We conclude that distribution dynamics of recombinant adenovirus after intra-CSF administration are excellent. However, because of the immune response elicited by the virus, even after administration to the CNS, development of immunomodulating strategies remains a challenge.

Adenoviridae↗

PubMed1999

Validity of prediction of the site of ruptured intracranial aneurysms with CT.

OBJECTIVE: We studied the diagnostic power of blood distribution on CT (performed within 72 hours after the bleed) for the site of ruptured aneurysm in 168 consecutive patients with subarachnoid hemorrhage with either a single aneurysm or no aneurysm on the four-vessel angiogram or postmortem examination. METHODS: A neurosurgeon and a neuroradiologist blind to the results of the angiography independently scored the distribution of blood on the CT and predicted the site of the ruptured aneurysm. RESULTS: Overall agreement among raters was 52% and chance-adjusted agreement (kappa) was 0.42 (weighted kappa value 0.47). A parenchymal cerebral hematoma was an excellent predictor for the site of a ruptured aneurysm but was present in only a minority of cases (15%). The next most valid predictor was blood distribution on CT in patients with a ruptured anterior cerebral artery aneurysm or anterior communicating artery aneurysm (sensitivity 0.79, specificity 0.96, and positive predictive value 0.79 for rater 1; sensitivity 0.77, specificity 0.97, and positive predictive value 0.90 for rater 2). The validity of the predictive value of blood distribution on CT in patients with a ruptured aneurysm of the middle cerebral artery, internal carotid artery, or posterior circulation arteries was either inconsistent between raters or low. CONCLUSION: With the exception of the presence of a parenchymal hematoma, the site of the ruptured aneurysm can be predicted by CT only in ruptured anterior cerebral artery or anterior communicating artery aneurysms.

Adult↗

PubMed1999

Genetic aberrations in oligodendroglial tumours: an analysis using comparative genomic hybridization (CGH).

Four low-grade oligodendrogliomas, nine anaplastic oligodendrogliomas and two mixed oligoastrocytomas were investigated for chromosomal aberrations by comparative genomic hybridization on formalin-fixed, paraffin-embedded tissue samples. The most frequent losses observed involved 1p, 9p, 10pq, 14q, 16p, 19q, while the most frequent gains were seen on 7pq, 11pq, 17p, 19pq, and Xp. In one oligodendroglioma, a highly specific amplification of 1q32.1 was seen. The frequent losses of 14q have not been reported previously. In the two cases of mixed oligoastrocytomas multiple gains and losses were found that did not show a clear overlap with the alterations found in the pure oligodendrogliomas.

Adult↗

PubMed1999

The prognostic importance of the volume of traumatic epidural and subdural haematomas revisited.

The size of a traumatic intracranial haematoma at the moment of diagnosis can be impressive. Haematoma thickness is an inaccurate estimator of haematoma volume, and association with patient outcome is controversial. In this study computerized volumetry of offline digitized CT scans was used to relate haematoma volume with both patient characteristics on admission and at the six months outcome. This retrospective study covered the time period 1981/1990. Ninety eight patients operated upon for an epidural haematoma and 91 patients operated upon for an acute subdural haematoma were analyzed. The relative importance of clinical data, CT scan parameters, and calculated haematoma volumes was determined by multivariate analysis. Volume of the haematoma did not correlate with preoperative neurological condition or the six months outcome in either group, and consequently is not of additional prognostic value.

Acute Disease↗

PubMed1999

Leptomeningeal metastasis after surgical resection of brain metastases.

OBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RESULTS: In this period 28 patients underwent surgery for brain metastasis, of whom 27 were available for evaluation in this study. Median survival after craniotomy was 11 months. Nine patients (33%) developed leptomeningeal metastasis 2-13 months after surgery, which included six of the nine patients operated on for posterior fossa metastasis (p=0.05). In five patients, leptomeningeal metastasis was the only site of recurrence. Three patients developed the leptomeningeal metastasis as bulky tumour along the spinal cord, which is a rare presentation. No other risk factors for the development of leptomeningeal metastasis other than surgery for posterior fossa metastasis were identified. CONCLUSIONS: There is an increased risk of leptomeningeal metastasis after surgery for posterior fossa metastasis. Future trials should consider the value of an active approach to this complication in these patients.

Adult↗

PubMed1998

Monitoring brain oxygen tension in severe head injury: the Rotterdam experience.

Cerebral ischemia is considered the central mechanism leading to secondary brain damage in patients with severe head injury. We investigated the technique of continuous monitoring of local brain tissue oxygen tension as parameter for cerebral oxygenation. Eighty-two patients with non penetrating severe head injury were studied. No complications of the monitoring technique were seen. Postmeasurement calibration of the catheters showed a very low zero drift and acceptable sensitivity drift. Low PbrO2 values were seen within the first 12 to 24 hours of injury. Early occurrence of values below 10 mm Hg indicated a poor prognosis. Comparative measurements between two catheters performed in six patients showed differences in absolute values measured, but a good correlation of relative changes was observed. We conclude that continuous monitoring of PbrO2 is reliable, clinically applicable and provides the clinician with a better insight in cerebral oxygenation and hopefully should help in targeting therapy towards improved cerebral oxygenation.

Brain Ischemia↗

PubMed1998

Does CSF outflow resistance predict the response to shunting in patients with normal pressure hydrocephalus?

The value of the measurements of CSF outflow resistance (Rcsf) relative to predicting outcome after shunting was studied. In a group of 101 patients with mainly idiopathic normal pressure hydrocephalus (NPH) Rcsf was obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified using an NPH scale (NPHS) and disability by the Modified Rankin scale (MRS). Patients were assessed before and at 1, 3, 6, 9 and 12 months after surgery. Outcome measures were differences between the preoperative and last NPHS and MRS scores. Improvement was defined as a change of > or = 15% in NPHS and > or = 1 grade in MRS. Intention-to-treat analysis of all patients at one year yielded improvement of 57% in NPHS and 59% in MRS. Efficacy analysis, excluding comorbidity unrelated to NPH, revealed positive predictive values of around 80% at Rcsf < 18, and between 90% and 100% at Rcsf > or = 18 mm Hg/ml/min. For Rcsf > or = 18, the likelihood ratios were also higher. We conclude that the best predictor of the response to shunting is an Rcsf > or = 18 mm Hg/ml/min. Since two-thirds of the patients with Rcsf < 18 showed improvement as well, these patients should not be denied shunting.

Cerebrospinal Fluid Pressure↗