Shunting to the sagittal sinus.

OBJECTIVES: To develop a shunt that drains CSF from the ventricles to the sagittal sinus under normal-physiological conditions. This shunting principle will not lead to any over-drainage, and a large proportion of the known shunt-complications will be avoided. METHODS: On the basis of the normal values for ICP, resistance to outflow and the production rate of CSF we have developed a shunt that drains CSF to the sagittal sinus and restores normal condition for the CSF dynamics. The shunt consists of two unidirectional valves, a pre-chamber, a resistance tube made of titanium, and a titanium tube leading CSF into the sagittal sinus. The shunt has been tested in 18 patients. Observation time ranged from 2 to 430 days, mean time 54 days. RESULTS: The first results from the use of the new shunt are very promising. It has an immediate effect on the clinical symptoms, it restores CSF dynamics (investigated with the shunt inserted) and the size of the ventricles is only gradually diminished. Slit ventricles have not yet been observed. In all patients the symptoms of hydrocephalus were relieved. No occlusion or thrombosis of the sagittal sinus have been observed. This is in agreement with the reports in the literature of shunting to the sagittal sinus, where 99 cases have been presented with an observation period of up to 6 years. The shunt has proven easy and safe to implant. CONCLUSIONS: Shunting to the sagittal sinus has proven easy and safe with regard to short term results. By using a dedicated shunt that drains at normal physiological parameters for the CSF dynamics any over-drainage is avoided, and it may be expected that the complication rate will be substantially smaller than with existing shunting systems.

Childhood medulloblastoma in Denmark 1960-1984. A population-based retrospective study.

Medulloblastoma is a common paediatric brain tumour, located in the cerebellum and in the IV ventricle, surpassed in frequency only by astrocytomas. 180 children below the age of 15 with a medulloblastoma of the posterior fossa were treated in Denmark in the 25-year period from 1960 to 1984 and followed up until the end of 1996, or until death. During the 25 years they accounted for 20% of all intracranial tumours in children in Denmark. All tumours were histologically verified. The mean annual incidence was 6.4x10(-6), decreasing slightly with a factor of 0.12x10(-6) per year. The male/female ratio was 2.1 - twice that of the background population of children (1.05). The 5-year survival rate following diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was 16%. The 5-year survival rate was 8% in the first 5-year period of 1960-1964, increasing to 36% in the last period 1980-1984. Presumably the increase in survival depends on many factors, e.g. improved diagnostic methods and neuroanaesthesia, better operative technique (microscope), improvements in radiotherapy and the introduction of chemotherapy. The best predictive factors of a good prognosis were preoperative CSF shunting, radical tumour removal and complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord. The survival rate in the last five-year period was seven times higher than the survival rate found in a comparable Danish study from the years 1935-1959. Most of the children followed Collins law of risk index. The results of treatment in children with medulloblastoma remain unsatisfactory. Accordingly, participation in international prospective studies of multimodal treatment should be encouraged, possibly using chemotherapy prior to surgery.

Epidemiology and prognosis in children treated for intracranial tumours in Denmark 1960-1984.

A total of 911 Danish children under 15 years of age were treated for an intracranial tumour in the 25-five year period 1960-1984. All cases were followed up to the end of 1994 or to emigration or death if one of these came sooner. The mean annual incidence was 32.5 per million children with a slight increase over the 25 years. The male/female ratio was 1.15 and close to the M/F ratio for the entire Danish population of children. Of the tumours, 46% were located in the supratentorial and 54% in the infratentorial compartment, and 94% were verified histologically. In order of frequency the most common types were astrocytomas (all grades, 35%), medulloblastomas (20%), ependymomas (14%), and craniopharyngiomas (5%). Total removal of the tumour was performed in 277 and partial removal, including biopsy, in 490 children. In 57 patients a shunt operation only was performed, and 87 children did not have an operation or died before the correct diagnosis was established. Radiotherapy was administered in 55%. The outcome depended on extent of removal, radiation, location and histology of the tumour. Most (784 or 86%) of the children survived more than 1 month after diagnosis or operation, and 353 children (39% of the whole series, 47% of those alive more than 1 month after diagnosis) were alive at follow-up. Of the survivors 29% had a tumour in the supratentorial midline, 26% one in the lateral part of the supratentorial area, 31% a cerebellar tumour and 13% a IV ventricle tumour. It was possible for 66% of the survivors with supratentorial and 90% of those with infratentorial tumours to lead a normal life. The long-term prognosis was especially good for children with cerebellar and supratentorial astrocytomas and optic chiasma tumours. Children with juvenile cerebellar astrocytoma had the best prognosis: 90% were alive at the end of the follow-up period, as against 20% of those with medulloblastoma and 6% of those with glioblastoma. A comparison of the data from the present series and from a similar Danish series of intracranial tumours in 533 children seen in the years 1935-1959 shows no significant differences in location or histology, a slight increase in annual incidence, and improved survival rates during the 50 years in question.

[Metastatic spinal cord compression in patients with lung cancer]. / Metastatisk spinalt tvaersnitssyndrom hos patienter med lungecancer.

Metastatic spinal cord compression (MSCC) is a disabling complication to cancer for which the optimal treatment of choice is not settled. An analysis was performed in patients with MSCC secondary to lung cancer in order to elucidate clinical symptoms and treatment results according to regression of neurological deficits and survival. The total series consisted of 102 retrospectively evaluated patients referred for treatment, in the Eastern part of Denmark in the period 1979-1988. Patients included 40% cases with Small Cell Carcinoma (SCLC), Adeno-carcinoma (ACL) (26%), Squamous Cell Carcinoma (SQLC) (18%) and Large Cell Carcinoma (LCC) (9%). Symptoms, clinical presentations and therapeutic results are described. The outcome of treatment depended fundamentally on the patient's neurological condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory while 15% of the non-ambulatory SCLC patients regained walking ability; in non-SCLC, 95% of patients retained walking ability while 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histological types of lung cancer as to the different treatment modalities were observed, however, 82% of the patients with non-SCLC had benefit from treatment with laminectomy followed by radiotherapy compared with either laminectomy (47%) or radiotherapy (39%) alone (p = .03, Chi-square test). The group of patients treated with laminectomy followed by radiotherapy had a better survival (median value 3.5 months, range 0-132 months) than patients treated with either laminectomy (median value 1.5 months, range 0-32 months) or radiotherapy (median value 1 month, range 0-59 months) alone (p = .03, Log-Rank test). No significant difference was observed in survival between the various histological types of lung cancer (p = .18, Log-Rank test). Despite a short survival, early diagnosis and immediate treatment is crucial, since it may preserve the gait function in 97% of lung cancer patients developing malignant spinal cord compression.

The effect of ketanserin on ICP and CBF in patients with normal-pressure hydrocephalus.

Eight patients with normal-pressure hydrocephalus were studied. Intracranial pressure (ICP) and mean arterial blood pressure (MAP) were measured continuously before and during administration of ketanserin i.v. (10 mg bolus followed by an infusion of 3 mg over a 60-min period, 6 mg over the next 30 min, and 12 mg over the last 30 min). The mean baseline MAP and ICP were 103 and 8 mm Hg, respectively. Five minutes after the bolus dose, the maximum decrease in MAP occurred (mean, 17 mm Hg; p < 0.05). The maximum ICP (10 mm Hg) occurred at 5 min and at 100 min after the bolus dose but was not significantly different from the baseline value. There was no change in relative global cerebral blood flow (CBF) expressed as 1/(arteriovenous oxygen difference). It is concluded that ketanserin in a clinically recommended dose decreases blood pressure without significantly influencing the ICP or CBF.

Cerebral blood flow velocity during high volume plasmapheresis in fulminant hepatic failure.

High volume plasmapheresis has previously been found to improve neurological statuses in patients with fulminant hepatic failure. We investigated the relationship between the neurological status and cerebral blood flow velocity (Vmean) during high volume plasmapheresis in 18 consecutive patients (ten females and eight males) with fulminant hepatic failure, with a mean age of 43 (range 9 to 57) years. The mean arterial pressure (MAP) and intracranial pressure (ICP) were also recorded. A total of 16% of body weight was exchanged with fresh frozen plasma per day. Thirty-six plasma exchanges wer performed with a median of 2 (range 1 to 8) per patient. Eleven of the patients survived (61%), nine after liver transplantation. Following the first high volume plasmapheresis, the coma score improved from 6 (1-8) to 2 (0-8) (p < 0.05), Vmean increased from 40 (14-152) to 62 (16-186) cm s-1 (p < 0.05), and MAP from 72 (35-118) to 94 (47-138) mmHg (p < 0.05). The intracranial pressure (ICP) was monitored and remained unchanged in nine patients whereas the cerebral perfusion pressure (MAP minus ICP) increased in the surviving group from 55 (40-74) to 80 (50-91) mmHg (p = 0.07) in contrast to no changes in the non survival group. In conclusion this study suggests that the neurological status, may improve during high volume plasmapheresis as MAP and Vmean increase the cerebral oxygen delivery.

The effect of tirilazad mesylate (U74006F) on cerebral oxygen consumption, and reactivity of cerebral blood flow to carbon dioxide in healthy volunteers.

BACKGROUND: The 21-aminosteroids are a series of compounds designed to inhibit lipid peroxidation in the cell, and, as such, may have cerebral protective effects. The current study was performed to evaluate the effect of a 21-aminosteroid, tirilazad mesylate (U74006F), on cerebral blood flow, metabolism, and carbon dioxide reactivity. METHODS: Using a double-blind study design, eight volunteers received tirilazad mesylate, and eight others received only vehicle. The cerebral blood flow was measured by single photon emission computerized tomography using 133Xe inhalation in the resting condition at the beginning of the study and after infusion of tirilazad mesylate (1.5 mg/kg) or vehicle. Cerebral oxygen metabolism was calculated from the cerebral blood flow and the measured cerebral arteriovenous oxygen content difference. After both of the above cerebral blood flow measurements, arterial carbon dioxide tension was decreased by voluntary hyperventilation, and, later, increased by breathing an air/carbon dioxide mixture. The relative changes in cerebral blood flow induced by the PaCO2 variations were estimated from the changes in the arteriovenous oxygen content difference. RESULTS: Blood pressure, pulse rate, and PaCO2 were similar before and after the infusion of tirilazad mesylate in both groups, and there was no difference between the groups. The cerebral blood flow and oxygen metabolism did not change after the tirilazad mesylate infusion. The slope of the regression line of relative change of estimated cerebral blood flow and PaCO2 (regression coefficients in both groups, > 0.90) was unchanged after infusion. CONCLUSIONS: Tirilazad mesylate has no effect on cerebral blood flow, cerebral oxygen metabolism, or reactivity of cerebral blood flow to carbon dioxide in healthy volunteers.

Metastatic spinal cord compression secondary to lung cancer.

PURPOSE: Metastatic spinal cord compression (MSCC) is a disabling complication to cancer, the optimal treatment for which is not settled. An analysis was performed for all patients with MSCC secondary to lung cancer in East Denmark from 1979 to 1988. PATIENTS AND METHODS: The total series included 102 cases with small-cell carcinoma (SCLC; 40%), adenocarcinoma (ACL; 26%), squamous cell carcinoma (SQLC; 18%) and large-cell carcinoma (LCC; 9%). Symptoms, clinical presentations, and therapeutic results are described. RESULTS: The outcome of treatment depended fundamentally on the patient's neurologic condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory, whereas 15% of the nonambulatory SCLC patients regained walking ability. In non-SCLC, 95% of patients continued to be able to walk, whereas 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histologic types of lung cancer and the different treatment modalities were observed; however, 82% of the patients with non-SCLC benefited from treatment with laminectomy followed by radiotherapy (RT) compared with either laminectomy (47%) or RT (39%) alone (P = .03, chi 2 test). The group of patients who were treated with laminectomy followed by RT had a better survival (median value, 3.5; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5; range, 0 to 32 months) or RT (median value, 1; range, 0 to 59 months) alone (P = .03, log-rank test). No significant difference was observed in survival between the various histologic types of lung cancer (P = .18, log-rank test). CONCLUSION: Despite a short survival, early diagnosis and immediate treatment is crucial because it may preserve the gait function in 97% of lung cancer patients who develop malignant spinal cord compression.

[Metastatic spinal compression syndrome. Symptoms, diagnosis, treatment and prognosis]. / Metastatisk spinalt tvaersnitssyndrom. Symptomer, diagnose, behandling og prognose.

A retrospective study of 398 patients suffering from metastatic compression of the spinal cord or cauda equina is presented. The study comprised almost all relevant medical records of patients admitted to hospital in the eastern part of Denmark in the period 1979 through 1985. Carcinoma of the lung, prostate, breast and kidney were the most frequent primary malignancies causing spinal compression. Most patients were treated with laminectomy, or radiotherapy or with laminectomy and radiotherapy combined. The effect of the treatment was estimated by evaluation of motor function and sphincter control. Treatment with laminectomy followed by radiotherapy was significantly superior to treatment with laminectomy or radiotherapy alone. But if the patients' motor function and primary tumour were taken into account, no significant difference between the treatments was observed. The efficacy of treatment depended upon the symptoms when the diagnosis was established, and accordingly early diagnosis is of the utmost importance. The incidence of metastatic compression increased during the period covered by the study, and since this condition must not go untreated, awareness of the symptoms, primarily pain, is essential.

Metastatic epidural spinal cord compression. Results of treatment and survival.

All medical records of patients treated for metastatic compression of the spinal cord or cauda equina in the eastern part of Denmark from 1979 through 1985 were reviewed. With regard to treatment response and survival, 345 patients could be evaluated. Carcinoma of the lung (19%), prostate (18%), breast (13%), and kidney (10%) were the most frequent primary malignancies causing spinal compression. The outcome of treatment depended primarily on the patients' condition at the time of diagnosis: 79% of the patients who were able to walk before the treatment remained ambulatory, whereas only 21% of the nonambulatory paraplegic patients and 6% of the paralytic patients regained walking ability. Patients treated with laminectomy followed by radiotherapy seemed to respond better than patients treated with radiotherapy or laminectomy alone, but when the patients' pretreatment motor function was taken into account no significant difference was found between the three forms of treatment. In the subgroup of nonambulatory patients, however, a significantly better restoration of gait was observed in patients treated with the combination of laminectomy and radiotherapy than in patients treated with radiotherapy alone. A longer survival in the group treated with the combination of laminectomy and radiotherapy may reflect that these patients were in a lower stage of disease and thus had a better potential of regaining motor function. The results call for prospective randomized studies.

Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations and prognosis in 398 patients with spinal cord compression.

We reviewed all medical records concerning patients suffering from spinal cord or cauda equina compression (SCC) secondary to cancer, in the eastern part of Denmark, from 1979 through 1985. During the period the incidence of SCC in cancer patients went up from 4.4% to 6%. However, this increase was not significant. The series comprised 398 cases, with carcinoma of the prostate (19%), lung (18%), breast (14%) and kidney (10%) accounting for 61%. The symptoms were evaluated in accordance with the patients rating of pain, motor deficits, sphincter control and paraesthesia, whereas the clinical manifestations were classified on the basis of motor deficit and bladder dysfunction. During the period preceding the diagnosis of SCC, 83% of the patients suffered from back pain, 67% from deteriorating gait and 48% had retention of the urine. In 35% of the patients there was no sphincter disturbance and 10% had normal sensory function. The outcome of treatment was estimated by changes in motor deficits and sphincter function, and depended primarily on the patients condition at the time of the diagnosis. Of the patients who were able to walk before treatment, 79% remained ambulatory, whereas only 18% of the non-ambulatory patients regained walking ability. Patients treated by decompressive laminectomy followed by radiotherapy apparently had a better response than patients treated with surgery or irradiation alone, but when the patients pre-treatment motor function was taken into account, no significant difference was observed. The study may call for a properly randomized trial with careful stratification of tumour biology, performance status and neurological deficits.

Sensitive and specific enzyme-linked immunosorbent assay for urokinase-type plasminogen activator and its application to plasma from patients with breast cancer.

An enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of human urokinase-type plasminogen activator (u-PA) in plasma and serum. Microtiter plates were coated with a monoclonal antibody and incubated with standard or sample. Bound u-PA was quantitated with polyclonal antibodies conjugated with biotin, followed by avidin-peroxidase. The assay was 10 times as sensitive as previously reported immunoassays, the detection limit being approximately 1 pg u-PA in a volume of 100 microliter, with a linear dose-response up to 15 pg u-PA. The assay detected active u-PA and its inactive proenzyme form equally well, and the recovery of both forms was higher than 90% in plasma. It also detected u-PA complexed with plasminogen activator inhibitor type 1. Various structurally related proteins, including t-PA, were tested, but no reaction was observed with proteins other than u-PA and its amino-terminal fragment. The intra-assay and interassay coefficients of variation for determination of u-PA in plasma were 7.6% and 8.4%, respectively. The ELISA was used to measure the concentration of u-PA in plasma from 34 healthy donors and 92 patients with breast cancer with a varying extent of disease. The mean value for the healthy donors was 1.1 +/- 0.3 ng/ml (SD) of u-PA in plasma. This value is substantially lower than those previously reported. The mean value for the patients with breast cancer was 1.3 +/- 0.4 ng/ml. This moderate increase was statistically significant at the 1% level. Approximately one quarter of the patients had plasma u-PA concentrations above the range observed for the healthy controls. There was a positive correlation between the mean u-PA plasma concentration and the extent of disease in different groups of patients.