Impact of early surgery after aneurysmal subarachnoid haemorrhage.

OBJECTIVES: To investigate the effect of early aneurysm surgery (<72 h) on outcome in patients with subarachnoid haemorrhage (SAH). MATERIALS AND METHODS: We studied two consecutive series of patients with aneurysmal SAH [postponed surgery (PS) cohort, n = 118, 1989-1992: surgery was planned on day 12 and early surgery (ES) cohort, n = 85, 1996-1998: ES was performed only in patients with Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis to assess outcome at 3 months. RESULTS: Favourable outcome (Glasgow Outcome Scale 4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly more often in the ES cohort. The occurrence of rebleeds was similar in both cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable outcome: 6.4, 95% confidence interval (CI) 1.0-39.8] and patients with both CSS <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5, 95% CI 1.1-99.4). CONCLUSIONS: Our results support the widely adopted practice of ES in good-grade SAH patients.

Risk factors for infections related to external ventricular drainage.

BACKGROUND: External ventricular drainage (EVD) is frequently used in neurosurgery for cerebrospinal fluid (CSF) drainage in patients with raised intracranial pressure. The major complication of this procedure is an EVD-related infection, i.e., meningitis or ventriculitis. The purpose of the present retrospective single centre study is to assess the possible causes of these infections. PATIENTS AND METHODS: Two hundred and twenty-eight patients were included in the period from January 1993 until April 2005. Patient and disease demographics, as well as EVD data, and the occurrence of infection were reviewed, compared, and included in a risk-analysis study. RESULTS: The population's mean age was 56 +/- 15 years and the sexes were equally distributed. Most frequently, the indication for EVD was hydrocephalus due to intraventricular haemorrhage (48.2%). An infection was documented in 23.2% of all patients. Duration of EVD drainage appeared to be a risk factor for infection (>11 days: OR 4.1; 95% CI 1.8-9.2, p = 0.001). CSF sampling frequency was also a significant risk-factor (no sampling: OR 0.2, 95% CI 0.2-0.5, p = 0.003). CONCLUSIONS: We found a relatively high percentage of EVD-related infections. After multivariate analysis there appears to be a relation with duration of drainage and frequent CSF sampling. As a result, a new EVD protocol is proposed in our institution that we believe will decrease the number of EVD-related infections to a minimum.

Safety and efficacy of frameless and frame-based intracranial biopsy techniques.

BACKGROUND: Frameless stereotaxy or neuronavigation has evolved into a feasible technology to acquire intracranial biopsies with good accuracy and little mortality. However, few studies have evaluated the diagnostic yield, morbidity, and mortality of this technique as compared to the established standard of frame-based stereotactic brain biopsy. We report our experience of a large number of procedures performed with one or other technique. PATIENTS AND METHODS: We retrospectively assessed 465 consecutive biopsies done over a ten-year time span; Data from 391 biopsies (227 frame-based and 164 frameless) were available for analysis. Patient demographics, peri-operative characteristics, and histological diagnosis were reviewed and then information was analysed to identify factors associated with the biopsy not yielding a diagnosis and of it being followed by death. RESULTS: On average, nine tissue samples were taken with either stereotaxy technique. Overall, the biopsy led to a diagnosis on 89.4% of occasions. No differences were found between the two biopsy procedures. In a multiple regression analysis, it was found that left-sided lesions were less likely to result in a non-diagnostic tissue sample (p = 0.023), and cerebellar lesions showed a high risk of negative histology (p = 0.006). Postoperative complications were seen after 12.1% of biopsies, including 15 symptomatic haemorrhages (3.8%). There was not a difference between the rates of complication after either a frame-based or a frameless biopsy. Overall, peri-operative complications (p = 0.030) and deep-seated lesions (p = 0.060) increased the risk of biopsy-related death. Symptomatic haemorrhages resulting in death (1.5% of all biopsies) were more frequently seen after biopsy of a fronto-temporally located lesion (p = 0.007) and in patients with a histologically confirmed lymphoma (p = 0.039). CONCLUSIONS: The diagnostic yield, complication rates, and biopsy-related mortality did not differ between a frameless biopsy technique and the established frame-based technique. The site of the lesion and the occurrence of a peri-operative complication were associated with the likelihood of failure to achieve a diagnosis and with death after biopsy. We believe that using intraoperative frozen section or cytologic smear histology is essential during a stereotactic biopsy in order to increase the diagnostic yield and to limit the number of biopsy specimens that need to be taken.

Human adenovirus type 35 vector for gene therapy of brain cancer: improved transduction and bypass of pre-existing anti-vector immunity in cancer patients.

Clinical trials in malignant glioma have demonstrated excellent safety of recombinant adenovirus type 5 (Ad5) but lack of convincing efficacy. The overall low expression levels of the Coxsackie and Adenovirus receptor and the presence of high anti-Ad5-neutralizing antibody (NAb) titers in the human population are considered detrimental for consistency of clinical results. To identify an adenoviral vector better suited to infect primary glioma cells, we tested a library of fiber-chimeric Ad5-based adenoviral vectors on 12 fresh human glioma cell suspensions. Significantly improved marker gene expression was obtained with several Ad5-chimeric vectors, predominantly vectors carrying fiber molecules derived from B-group viruses (Ad11, Ad16, Ad35 and Ad50). We next tested Ad35 sero prevalence in sera derived from 90 Dutch cancer patients including 30 glioma patients and investigated the transduction efficiency of this vector in glioma cell suspensions. Our results demonstrate that the sero prevalence and the titers of NAb against Ad35 are significantly lower than against Ad5. Also, recombinant Ad35 has significantly increased ability to transfer a gene to primary glioma cells compared to Ad5. We thus conclude that Ad35 represents an interesting candidate vector for gene therapy of malignant glioma.

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.

[High level of satisfaction among patients despite persistent symptoms in the mid-long-term following surgery for lumbosacral radicular syndrome]. / Na operatie wegens lumbosacraal radiculair syndroom bij meer dan de helft van de patiënten nog klachten op middellange termijn, maar wel grote tevredenheid.

OBJECTIVE: To determine the mid-long-term outcomes after surgery in patients with lumbosacral radicular syndrome (LRS) and to identify prognostic factors for persisting LRS symptoms. DESIGN: Descriptive retrospective and prospective. METHOD: A total of 250 consecutive patients operated on by 7 neurosurgeons in four hospitals between May and December 2001 were selected from medical records. They were asked to take part in a telephone questionnaire at 6 and 19 months after operation. They had all undergone discectomy for LRS at L4-L5 or L5-S1 and were aged from 18 to 65. RESULTS: Of the 250 patients, 163 participated in the study: 63% reported that they still had LRS-related symptoms 19 months after surgery. However, severe leg pain had decreased in 83% of the patients. In general the patients were satisfied with their treatment. Female gender and an age of 51-65 were prognostic factors for persistent LRS symptoms. CONCLUSION: More than half of the patients reported LRS symptoms 19 months after surgery.

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.

Herpes simplex virus thymidine kinase gene therapy for rat malignant brain tumors.

Transfer of a herpes simplex virus-derived thymidine kinase (HSV-tk) gene into brain tumor cells and subsequent ganciclovir (GCV) treatment has been shown by others to be an effective treatment in rats with intracerebrally inoculated 9L gliosarcomas. Mechanism of action and reproducibility are, however, still a matter of debate. We have used the same model to test the therapeutic effects of both retrovirus- and adenovirus-mediated transfer of the HSV-tk gene followed by GCV treatment. Survival time of rats with intracerebral 9L tumors was significantly prolonged after a single administration of adenovirus carrying a HSV-tk gene as compared to controls. Retrovirus-mediated gene transfer also resulted in significantly prolonged survival time when recombinant retrovirus-producing cells were transplanted. Direct injection of the recombinant retrovirus, HSV-tk-expressing cells, virus-producing cells without GCV administration and recombinant retrovirus-lacZ or interleukin-2 (IL-2)-producing cells did not result in tumor cell kill. In the present study, no significant difference in survival of 9L brain tumor carrying rats was found after treatment with adenovirus as compared to retrovirus-mediated HSV-tk-mediated gene transfer and subsequent GCV treatment.

Cytogenetic, molecular genetic and pathological analyses in 126 meningiomas.

In a series of 126 meningiomas, tumor and patient characteristics were investigated and statistically analyzed. A combined cytogenetic and molecular genetic approach was used to study chromosomal abnormalities and loss of markers on chromosome 22q. This approach was successfully applied to 93 meningiomas. In 66 cases, complete or partial loss of chromosome 22 was observed and in at least 12 of them this chromosome was involved in structural aberrations. In addition to chromosome 22 changes, chromosomes 1, 6, 11, 13, 14, 18, 19, X, and Y were also frequently involved in structural and numerical aberrations. Statistical analysis revealed a significant association between the number of chromosomal abnormalities and tumor grade. Complex karyotypes predominated in the group of grade II/III meningiomas. Furthermore, other variables showed statistically (or marginally statistically) significant differences. Meningiomas from the convexity were more often grade II/III, displayed predominantly (partial) loss of chromosome 22 and had complex karyotypes more often. These features were frequently found in meningiomas from males. Base meningiomas, on the other hand, occurred more often in females; they were usually grade I, showed loss of (parts of) chromosome 22 less often and displayed fewer additional chromosomal abnormalities.

Somatostatin inhibits the activity of adenylate cyclase in cultured human meningioma cells and stimulates their growth.

It has been reported previously that most human meningiomas have receptors for somatostatin. Here we report the results of investigations of the effect of somatostatin and the somatostatin analog octreotide on the growth in vitro of human meningioma cells. Neither somatostatin nor its analog showed a direct growth inhibitory action on cultured human meningioma cells. Rather, there was a slight but significant stimulation of growth in the presence of somatostatin. The somatostatin receptors in meningioma tissue were shown to be functional since somatostatin inhibited forskolin-stimulated formation of cAMP by meningioma membranes. In addition, cAMP inhibited the growth of cultured meningioma cells. We conclude that the stimulation by somatostatin of the growth of human meningioma cells in vitro is caused by its inhibitory effect on cAMP formation. These results suggest that therapeutic trials of patients with (recurrent) inoperable meningiomas with somatostatin analogs have to be carried out with great caution.

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.

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.

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.

Inhibition of the growth of cultured human meningioma cells by recombinant interferon-alpha.

In this paper the results of investigations on the effect of interferon-alpha (IFN-alpha) on the growth of meningioma cells in culture is reported. A consecutive series of six meningiomas and one meningioma/neurofibroma derived from a patient with neurofibromatosis type 2 was investigated and it was found that the growth of all seven tumours in response to mitotic stimuli (fetal bovine serum or epidermal growth factor) is strongly inhibited by IFN-alpha. Maximal response varied between 100% and 70% inhibition of the incorporation of tritiated thymidine. In some cases an inhibitory response was obtained already at very low doses (less than or equal to 10 U of IFN-alpha per ml). These results indicate that further clinical investigation of the application of IFN-alpha to the treatment of meningioma is warranted.

Progesterone, oestradiol, somatostatin and epidermal growth factor receptors on human meningiomas and their CT characteristics.

The presence of progesterone, oestrogen, somatostatin and epidermal growth factor receptors of 24 meningiomas was related with their radiological CT appearance. Progesterone receptors were present in 16 of 21 (76%), oestrogen receptors in 4 of 21 (19%), somatostatin receptors on 23 of 24 (96%) and epidermal growth factor receptors on 17 of 19 (89%) meningiomas. There was no relationship between the presence of these receptors and the age or sex of the patients, tumour histology, tumour localisation, the presence of perifocal oedema, displacement of the midline cerebri or obstructive hydrocephalus on CT scan. There was a negative correlation (P less than 0.05) between the number of progesterone receptors and "malignant" behaviour of the meningiomas on CT (e.g. the presence of necrosis, cyst formation, intratumoral haemorrhage, irregular surface and/or inhomogeneous attenuation of contrast). The observation that aggressive tumour behaviour on CT is accompanied by low numbers or absence of progesterone receptors makes these meningiomas less attractive candidates for medical therapy with antiprogestins.

Brain parenchyma/pO2 catheter interface: a histopathological study in the rat.

Local cerebral oxygenation can be monitored continuously using an intraparenchymal Clark-type pO2 sensitive catheter. Measured values of brain tissue pO2 (PbrO2) not only depend on the clinically interesting balance between oxygen offer and demand, but also on catheter properties and characteristics of the probe tissue interface. Microdamage surrounding pO2-sensitive needles, inserted into various tissues, has been reported; we evaluated histologic changes at the probe tissue interface after insertion of pO2 probes, suitable for clinical use, in the rat brain. The effect of insertion of the probe itself (mechanical damage), the application of micropotential during the measurements, and the effect of time was evaluated using digital image analysis of H&E-stained histological slices. Surrounding the probe tract, a zone of edema with an average radius of 126.8 microm was seen; microhemorrhages with an average surface area of 56.2 x 10(3) microm2 were observed in nearly all cases. The area of edema and the presence of microhemorrhages were not influenced by performed measurements or by time. Intraventricular blood was observed in 10 of 19 rats studied. Measured low PbrO2 values were related to the presence of a microhemorrhage in either probe tract or ventricles. Tissue damage due to the measurements is negligible, and the amount of edema itself does not influence the accuracy or response time of the pO2 probe. Low PbrO2 readings, however, could be caused by local microhemorrhages, undetectable on CT or MRI.

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.

Cerebrospinal fluid pulse pressure and the pulsatile variation in cerebral blood volume: an experimental study in dogs.

The cerebrospinal fluid pulse pressure (CSFPP) has found application as a measure of intracranial elastance. However, CSFPP is also dependent on the magnitude of the pulsatile variation in cerebral blood volume (delta Vb). The purpose of the present study was to assess the effect on delta Vb of changes in systemic arterial pressure (SAP) and arterial carbon dioxide tension (PaCO2) as well as elevation of intracranial pressure (ICP). Therefore, delta Vb was computed from the electromagnetically measured flow profile in the vertebral artery of the dog on the assumption of a nonpulsatile cerebral venous outflow. During arterial hypotension, delta Vb was increased due to a shift of flow from diastole to systole, whereas mean flow was not affected. The reverse phenomenon was observed when SAP was raised. Changes in PaCO2 had little effect on pulsatile blood flow. The changes in total blood flow that occurred were evenly distributed over the cardiac cycle. Consequently, delta Vb was not significantly affected, although CSFPP was considerably changed. When ICP was raised, a breakpoint pressure was observed above which cerebral blood flow (CBF) decreased and CSFPP and delta Vb increased. This contradiction was explained by the finding of a decrease in diastolic flow, causing the fall in CBF, whereas systolic flow relative to mean flow was increased, resulting in an increased delta Vb. The underlying mechanisms of the pulsatile flow changes are extensively discussed. It is argued that the arterial inflow profile is largely determined by the compliance of the inflow section of the cerebral vascular bed. Vascular compliance is significantly altered by changes in SAP and ICP because they affect the transmural pressure of the vessels, whereas this is not the case during changes in PaCO2.

Continuous monitoring of partial pressure of brain tissue oxygen in patients with severe head injury.

Ischemia is one of the major factors causing secondary brain damage after severe head injury. We have investigated the value of continuous partial pressure of brain tissue oxygen (PbrO2) monitoring as a parameter for cerebral oxygenation in 22 patients with severe head injury (Glasgow Coma Scale score, < or = 8). Jugular bulb oxygenation, intracranial pressure, and cerebral perfusion pressure were simultaneously recorded. O2 and CO2 reactivity tests were performed daily to evaluate oxygen autoregulatory mechanisms. PbrO2 monitoring was started an average of 7.0 hours after trauma with a mean duration of 74.3 hours. No complications were seen, and the calibration of the catheters after measurement showed a zero drift of 1.2 +/- 0.8 mm Hg and a sensitivity drift of 9.7 +/- 5.3%. In 86% of patients, PbrO2 was < 20 mm Hg in the acute phase. Mean PbrO2 significantly increased during the first 24 hours after injury. Two distinct patterns of change of PbrO2 over time were noted. The first pattern was characterized by normal stable levels after 24 hours, and the second was characterized by transiently elevated levels of PbrO2 during the second and third days. PbrO2 values < or = 5 mm Hg within 24 hours after trauma negatively correlated with outcome. O2 reactivity was significantly lower in patients with good outcomes. CO2 reactivity showed no constant pattern of change over time and was not correlated with outcome. Increased hyperventilation was shown to decrease PbrO2 in some patients. Accurate detection of the moment of cerebral death was possible on the basis of the PbrO2 measurements. The correlation between PbrO2 and other parameters, such as intracranial pressure and cerebral perfusion pressure, was weak. We conclude that PbrO2 monitoring is a safe and clinically applicable method in patients with severe head injury. The early occurrence of ischemia after head injury can be monitored on a continuous basis. Deficiency of oxygen autoregulatory mechanisms can be demonstrated, and their occurrence is inversely related to outcome. For practical clinical use, the method seemed to be superior to jugular oximetry.

Sagittal sinus occlusion, caused by an overlying depressed cranial fracture, presenting with late signs and symptoms of intracranial hypertension: case report.

A case of delayed signs of intracranial hypertension after open depressed cranial fracture occluding the superior sagittal sinus is reported. Elevating depressed fractures overlying a cranial venous sinus is hazardous. Conservative management of the intracranial hypertension, including repeated lumbar punctures, led to an unimpaired outcome. The options of management of delayed problems caused by traumatic venous occlusion are discussed.