CME for neurosurgeons in the Netherlands: the "quality" conferences.

In 1993 the Netherlands Society for Neurosurgery started a yearly event, a "Quality Conference", specifically devoted to continuous medical education (CME). These conferences differ from "normal" scientific meetings, in the choice for specific topics, in the preparation with inquiries among all the Dutch neurosurgical centres, and in the way the results of these inquiries are discussed, preceded by lectures concerning the chosen topic by guest faculty and Dutch neurosurgeons. Each year's principal guest delivers the "Beks Lecture", named after the former professor in Neurosurgery in Groningen, Jan Beks. On several occasions, the foreign guests suggested to present this format for a larger neurosurgical forum. Therefore, it was decided to describe the various aspects of this format for CME in the Netherlands in a paper for Acta Neurochirugica. Examples of topics are given, a summary of two recent inquiries are presented and discussed, and the way of organizing such a conference including finance and the obligatory character are described.

Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in The Netherlands.

BACKGROUND: There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. METHOD: In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. CONCLUSIONS: In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment.

BACKGROUND: Magnesium is a neuroprotective agent which might prevent or reverse delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Although the dosage for short-term magnesium therapy is well established, there is lack of knowledge on the dosage for extended use of magnesium. Our aim was to find a dosage schedule of magnesium sulphate to maintain a serum magnesium level of 1.0-2.0 mmol/L for 14 days to cover the period of DCI. METHODS: We prospectively studied 14 patients admitted within 48 hours after aneurysmal subarachnoid haemorrhage (SAH) to our hospital. Magnesium sulphate was administrated intravenously for 14 days, using 3 different dosage schedules. Group A (n=3) received a bolus injection of 16 mmol magnesium sulphate followed by a continuous infusion of 16 mmol/daily; group B (n=6) a continuous infusion of 30 mmol/daily; and group C (n=5) a continuous infusion of 64 mmol/daily. Serum magnesium was measured at least every two days and all patients were under continuous observation during magnesium treatment. Renal magnesium excretion was measured only in group C. FINDINGS: In treatment group A the mean serum magnesium level during treatment was 1.03+/-0.14 (range 0.82-1.34) mmol/L, in group B 1.10+/-0.15 (range 0.87-1.43) mmol/L, and in group C 1.38+/-0.18 (range 1.11-1.98) mmol/L. The renal magnesium excretion in group C was equal to the administrated doses within 48 hours after treatment had started. All patients in group A reported a flushing sensation during the bolus injection; no other side effects were noted. INTERPRETATION: With a continuous intravenous dosage of 64 mmol/L per day, serum magnesium levels maintained within the range of 1.0-2.0 mmol/L for 14 days.

Direct costs of modern treatment of aneurysmal subarachnoid hemorrhage in the first year after diagnosis.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the current direct costs of modern management of patients with aneurysmal subarachnoid hemorrhage in the first year after diagnosis. METHODS: During a 1-year period, we studied all admitted patients with subarachnoid hemorrhage from a population of 2 million people. We calculated the direct costs of treatment, which included the costs of medical and nursing care and the related travel expenses of patients. We calculated true costs for all major healthcare resources. National census data, if available, and standard charges were used to determine healthcare resource expenses. RESULTS: Hospital admissions and diagnostic and therapeutic interventions in 110 patients accounted for 85% of all costs; 64% of the total direct medical costs during admission were the medical, nursing, and overhead costs alone. Patients discharged directly to home generated 4% of the total budget, whereas admission to a nursing home accounted for the remaining 11% of the total costs. Of the diagnostic and therapeutic costs, 45% was caused by imaging and 42% by surgery or coiling. Angiography alone accounted for 52% of the total imaging costs and 24% of the total diagnostic and therapeutic costs. Prescribed medication accounted for only 3% of the total budget of diagnostic and therapeutic costs. CONCLUSIONS: Most direct costs during the first year after aneurysmal subarachnoid hemorrhage are caused by the hospital inpatient days, accounting for two thirds of the total costs generated during the first year after the initial bleeding. If new costly treatments succeed in reducing the average length of inpatient hospital stays, then progress in therapy may prove cost effective and might even be cost saving.

High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin.

The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because recent studies on Daunorubicin in liposomes in the treatment of Kaposi sarcoma have shown effectiveness with diminished systemic toxicity, we administered intravenously a single dose of Daunorubicin in liposomes in eight patients at different intervals prior to surgery (12-50 h). In samples taken from tumor, tumor-edge and where possible from adjacent brain, the levels of Daunorubicin and its active metabolite Daunorubicinol were assessed with high performance liquid chromatography. Here we report that high concentrations of Daunorubicin and Daunorubicinol were found in malignant gliomas after systemic administration of liposomal Daunorubicin.

Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands.

OBJECTIVE: The aim of this study was to investigate prospectively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are, what the outcome is, how many of these patients have "modern treatment"-that is, early obliteration of the aneurysm and treatment with calcium antagonists-what factors cause a delay in surgical or endovascular treatment, and what the estimated effect on outcome will be of improved treatment. METHODS: A prospective, observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherlands. The condition on admission, diagnostic procedures, and treatments were recorded. If a patient had a clinical deterioration, the change in Glasgow coma score (GCS), the presence of focal neurological signs, the results of additional investigations, and the final diagnosed cause of the deterioration were recorded. Clinical outcome was assessed with the Glasgow outcome scale (GOS) at 3 month follow up. In patients with poor outcome at follow up, the cause was diagnosed. RESULTS: Of the 110 patients, 47 (43%) had a poor outcome. Cerebral ischaemia, 31 patients (28%), was the most often occurring complication. Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34% and 30% of the patients with poor outcome respectively. Of all patients 102 (93%) were treated with calcium antagonists and 45 (41%) patients had early treatment to obliterate the aneurysm. The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission, in 31% and 23% respectively. CONCLUSIONS: In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding. Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage.

MR angiography as a screening tool for intracranial aneurysms: feasibility, test characteristics, and interobserver agreement.

OBJECTIVE: MR angiography may be an appropriate tool to screen for unruptured intracranial aneurysms. Feasibility, test characteristics, and interobserver agreement in evaluation of MR angiograms were assessed by members of the MARS (Magnetic resonance Angiography in Relatives of patients with Subarachnoid hemorrhage) Study Group. SUBJECTS AND METHODS: We screened 626 first-degree relatives of a consecutive series of 193 patients with subarachnoid hemorrhage examined at two institutions. We used MR imaging and MR angiography (three-dimensional time-of-flight imaging at both institutions and additional three-dimensional phase-contrast imaging at one institution). Three observers independently assessed the MR angiograms. Conventional angiography was performed in relatives with possible or definite aneurysms on MR angiography and was considered the standard of reference. RESULTS: Thirty-three aneurysms were found in 25 (4%; 95% confidence interval [CI], 3-6%) of 626 relatives. Thirteen (8%) of 169 relatives who refused screening had MR-related reasons; an additional six persons could not be screened because of contraindications for MR imaging (pregnancy, n = 1; claustrophobia, n = 5). The positive predictive value of MR angiography was 100% (95% CI, 79-100%) for "definite" aneurysms and 58% (95% CI, 28-85%) for "possible" aneurysms. Sensitivity of MR angiography was estimated at 83% (95% CI, 65-94%) and specificity at 97% (95% CI, 94-98%). Interobserver agreement in the evaluation of MR angiograms was poor (kappa < .30), probably because different diagnostic strategies used by individual observers resulted in different use of the assessment category "possible aneurysm." CONCLUSION: MR angiography is a feasible screening tool for detection of intracranial aneurysms. Positive predictive value, sensitivity, and specificity are acceptable when at least two neuroradiologists independently assess MR angiograms.

Type III collagen deficiency in saccular intracranial aneurysms. Defect in gene regulation?

BACKGROUND AND PURPOSE: We sought to determine whether there are mutations in the COL3A1 gene in patients with saccular intracranial aneurysms with a type III collagen deficiency and whether there is an association between a marker in the COL3A1 gene and saccular intracranial aneurysms. One of the heritable factors possibly involved in the pathogenesis of saccular intracranial aneurysms is a reduced production of type III collagen, demonstrated earlier by protein studies. METHODS: We analyzed the type III collagen gene in a group of 41 consecutive patients with an intracranial aneurysm, of whom 6 patients had shown a reduced production of type III collagen in cultured diploid fibroblasts from a skin biopsy. RESULTS: No mutations could be demonstrated in the COL3A1 gene, especially not in the globular N- and C-terminal regions. A null allele was excluded in 25 patients, including 1 patient with a decreased type III collagen production. No differences were found between 41 patients and 41 controls in allele frequencies of a DNA tandem repeat polymorphism located in the COL3A1 gene. CONCLUSIONS: It is concluded that the COL3A1 gene is not directly involved in the pathogenesis of most of intracranial aneurysms. The reduced type III collagen production in cultured fibroblasts found in some patients with an intracranial aneurysm is not explained by the present study and needs further exploration.

Primary nerve-sheath tumours of the trigeminal nerve: clinical and MRI findings.

We reviewed the clinical and MRI findings in primary nerve-sheath tumours of the trigeminal nerve. We retrospectively reviewed the medical records, imaging and histological specimens of 10 patients with 11 primary tumours of the trigeminal nerve. We assessed whether tumour site, size, morphology or signal characteristics were related to symptoms and signs or histological findings. Histological proof was available for 8 of 11 tumours: six schwannomas and two plexiform neurofibromas. The other three tumours were thought to be schwannomas, because they were present in patients with neurofibromatosis type 2 and followed the course of the trigeminal nerve. Uncommon MRI appearances were observed in three schwannomas and included a large intratumoral haemorrhage, a mainly low-signal appearance on T2-weighted images and a rim-enhancing, multicystic appearance. Only four of nine schwannomas caused trigeminal nerve symptoms, including two with large cystic components, one haemorrhagic and one solid tumor. Of the five schwannomas which did not cause any trigeminal nerve symptoms, two were large. Only one of the plexiform neurofibromas caused trigeminal nerve symptoms. Additional neurological symptoms and signs, not related to the trigeminal nerve, could be attributed to the location of the tumour in three patients.

Intraoperative changes of transcranial Doppler velocity: relation to arterial oxygen content and whole-blood viscosity.

The association of arterial oxygen content (CaO2) and viscosity with transcranial Doppler (TCD) blood flow velocity in the middle cerebral artery was studied in 20 adults without cerebrovascular disease undergoing abdominal surgery associated with significant fluctuations in hematology. TCD measurements and arterial blood samples were obtained before and directly after surgery but before blood transfusion. There was an inverse association between baseline mean velocity and CaO2 (r = -0.56), hematocrit (r = -0.50), hemoglobin (r = -0.51), and high-shear viscosity (r = -0.46). After intraoperative blood loss, intraindividual fluctuations of TCD measurements, blood oxygenation, and rheologic factors were studied. In multiple regression analysis, changes in CaO2 had the strongest association with changes in TCD values, accounting for 55% of the variation in mean velocity. Addition of hematocrit and viscosity could not account for more variation in mean velocity than CaO2 alone.

[Two children with unusual causes of torticollis: primitive neuroectodermal tumor and Grisel's syndrome]. / Twee kinderen met bijzondere oorzaken van dwangstand van het hoofd: primitieve neuro-ectodermale tumor en syndroom van Grisel.

Two children were presented with a torticollis. One, a 2-year-old girl, had a primitive neuroectodermal tumour of the cervical spinal cord which could not be radically removed surgically (the patient died three days later), the other, a 9-year-old boy, had the syndrome of Grisel. He was treated with antibiotics, head traction and atlantoaxial posterior spondylodesis. Acquired torticollis is a frequent innocent symptom in children with cervical lymphadenopathy following a respiratory tract infection. These cases demonstrate that additional investigation should not be delayed if relief of symptoms is not achieved very soon.

Some patients with intracranial aneurysms have a reduced type III/type I collagen ratio. A case-control study.

A reduced production of type III collagen has been reported in previous studies to be associated with intracranial aneurysms. The purpose of this prospective case-control study was to assess the possible role of a reduced type III collagen production as a risk factor for having an intracranial aneurysm. The study group consisted of 41 consecutively admitted patients with intracranial aneurysms. Intracranial aneurysms were demonstrated by intraarterial digital subtraction cerebral angiography or during operation. The control group consisted of 41 healthy volunteers matched for age and sex. Fibroblasts were cultured from skin biopsies from patients and control subjects, and the type III/type I collagen ratios were determined. The type III/type I collagen ratios in the controls ranged from 5.5 to 19.8%, with a median ratio of 10%, and none had a ratio below 5.5%. The type III/type I collagen ratios in patients ranged from 1.1 to 25.1%, with a median ratio of 10.5%, and eight patients (19.5%) had a low (< 5.5%) ratio (p = 0.005, Fisher's exact test). Our findings support the hypothesis that a reduced production of type III collagen may contribute to the formation of intracranial aneurysms in some patients.

Timing of surgery in patients with aneurysmal subarachnoid haemorrhage: rebleeding is still the major cause of poor outcome in neurosurgical units that aim at early surgery.

OBJECTIVE: To investigate prospectively the proportion of patients actually operated on early in units that aim at surgery in the acute phase of aneurysmal subarachnoid haemorrhage (SAH) and what is the main current determinant of poor outcome. METHODS: A prospective analysis of all SAH patients admitted during a one year period at three neurosurgical units that aim at early surgery. The following clinical details were recorded: age, sex, date of SAH, date of admission to the neurosurgical centre, whether a patient was referred by a regional hospital or a general practitioner, Glasgow coma scale and grade of SAH (World Federation of Neurological Surgeons (WFNS) score) on admission at the neurosurgical unit, results of CT and CSF examination, the presence of an aneurysm on angiography, details of treatment with nimodipine or antifibrinolytic agents, and the date of surgery to clip the aneurysm. At follow up at three months, the patients' clinical outcome was determined with the Glasgow outcome scale and in cases of poor outcome the cause for this was recorded. RESULTS: The proportion of patients that was operated on early--that is, within three days after SAH--was 55%. Thirty seven of all 102 admitted patients had a poor outcome. Rebleeding and the initial bleeding were the main causes of this in 35% and 32% respectively of all patients with poor outcome. CONCLUSIONS: In neurosurgical units with what has been termed "modern management" including early surgery, about half of the patients are operated on early. Rebleeding is still the major cause of poor outcome.