Second surgery for progressive glioblastoma: a multi-centre questionnaire and cohort-based review of clinical decision-making and patient outcomes in current practice.

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

Kernohan-Woltman notch phenomenon: a review article.

Kernohan-Woltman notch phenomenon (KWNP) is a false localising sign which may still cause diagnostic confusion. It was first described by Kernohan and Woltman in 1929, through post-mortem studies on 297 patients following cases of false localisation. They proposed that raised intracranial pressure causes uncal herniation, which can compress the contralateral cerebral peduncle against the tough tentorium, manifesting as hemiparesis ipsilateral to the primary brain lesion. A number of case reports have been written since the original description of this phenomenon, primarily secondary to intracranial bleeds, and little has been written about long-term outcome of patients who develop KNWP. We performed a literature search of all published cases of KWNP, and reviewed its clinical, pathophysiological, imaging and neurophysiological characteristics. Furthermore, we summarise the long-term outcomes of these patients as described by case reports, with the aim to improve understanding of rehabilitation potential. Thirty-eight cases were found through a PubMed search. We also included a case from our own Trust, making the total number of cases in the analysis 39. Thirty-six cases were secondary to intracranial bleeds (22 of which were traumatic), the remainder were due to an arachnoid cyst, high grade glioma, and reabsorption bone syndrome. Additional clinical manifestations to hemibrachiocrural syndrome included third nerve palsy, mydriasis of the contralateral and ipsilateral pupils, facial nerve palsies, and parkinsonism. Twenty-six (67%) patients had improvement in motor function of varying degrees, with twelve (31%) patients attaining complete motor recovery or independence. More studies on long-term outcome of patients who develop KWNP are needed to understand rehabilitation potential.

Internal carotid blood flow and cerebral hemispheric perfusion in patients with subarachnoid haemorrhage: a study of the quantix/NDtrade mark system and CT perfusion technology.

OBJECTIVE: To assess whether carotid blood flow measurements predict abnormalities in cerebral hemispheric perfusion. DESIGN: The Quantix/NDTM system was used to measure carotid artery blood flow in nine patients with subarachnoid haemorrhage who underwent CT perfusion scanning. RESULTS: No significant correlation was found between internal carotid artery blood flow and ipsilateral cerebral hemispheric perfusion (013, p>0.05) but there was a statistically significant correlation between total internal carotid and global cerebral perfusion (0.63, p<0.05). CONCLUSIONS: This is the first report comparing the Quantix/NDTM system with CT perfusion. Our data do not show a statistically significant correlation between extracranial blood flow and cerebral hemispheric perfusion. This is in contrast to two previous studies where Quantix/NDTM measurements were compared with measurements of cerebral perfusion using the Xenon clearance technique.

Intralobular variations in barrier thickness in the mature human placenta.

Following perfusion fixation, the harmonic mean thickness of the villous membrane was measured for terminal villi sampled at various sites within a single lobule. Comparisons were made between central and peripheral regions of the lobule at the levels of the basal plate, the mid-zone and just under the chorionic plate. Ten placentae were examined, and in each case the centre of a lobule was identified by the presence of a villus-free cavity. At each level the harmonic mean thickness was significantly reduced in the peripheral regions compared to the central regions. By contrast, no change was found in the arithmetic mean thickness, the volume fraction of the fetal capillary lumina, or the mean capillary diameter. This variation in harmonic mean barrier thickness may be related to the pattern of maternal blood flow through the lobule and any PO2 gradient that results therefrom. It is clear that changes in the thickness of vasculosyncytial membranes can take place independently of any alterations in the calibre of the underlying fetal capillary network.

Rapid molecular mass and structural determination of plant cell wall-derived oligosaccharides using off-line high-performance anion-exchange chromatography/mass spectrometry.

A method has been developed for the rapid molecular mass determination and structural elucidation of mixtures of oligosaccharides derived from plant cell walls. The oligosaccharides were fractionated using gel permeation chromatography and 'analytical' high-performance anion-exchange chromatography (HPAEC), neutralized, dried and the mixtures of eluent salt and oligosaccharides were per-O-acetylated directly. The derivatized oligosaccharides were isolated by dissolution in dichloromethane and the salts were removed by aqueous partitioning. The per-O-acetylated oligosaccharides were analysed using electrospray (ES) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MS). Exploiting the fact that acid-catalysed per-O-acetylation of oligosaccharides can be achieved even under the extremely salty conditions that are found in post-column neutralized HPAEC fractions, and combining this derivatization step with off-line ESMS, allow rapid screening for molecular mass and thus yield information on the composition of the various oligosaccharides in these complex mixtures. Subsequent per-O-methylation of the per-O-acetylated, salt-free fractions and collision-induced dissociation tandem mass spectrometric analysis was used for additional sequence and branching determination of the oligosaccharides.

Cerebral trypsinogen expression in human and rat cerebrospinal fluid.

Trypsinogen was identified in cerebrospinal fluid (CSF), where it has not previously been reported and its activation state in experimental subarachnoid haemorrhage (SAH) in rats and in neurosurgical patients was determined. Trypsinogen activation peptide (TAP) release provided an equimolar marker for trypsinogen. Total TAP was significantly reduced to 26% of the baseline level (P<0.02) following experimental SAH in 15 rats but not in ten sham operated controls (P=0.3). TAP was also measured in patients with ruptured (n=11) and unruptured (n=9) aneurysms who underwent craniotomy to clip an aneurysm. Postoperatively there was a significant fall in TAP concentration (P<0.005) in both groups. Trypsinogen, as identified by CSF levels of TAP, is activated by SAH in rats and by craniotomy for aneurysmal clipping in patients.

Cerebral blood flow and tissue oxygenation monitoring during aneurysm surgery.

Regional cerebral blood flow may be compromised during aneurysm surgery. This may occur during vessel occlusion by temporary clips or result from malposition of the definitive aneurysm clip. Post-operative cerebral vasospasm may also compromise cerebral blood flow and is an important cause of morbidity. This study addresses the need for a sensitive indicator of compromised cerebral function during aneurysm surgery by measuring brain tissue oxygenation and laser Doppler flow. Four patients were studied, all of whom had ruptured middle cerebral artery aneurysms. Brain tissue oxygenation measurements were made with a closed polarographic sensor placed in the ipsilateral cerebral hemisphere to the aneurysm. A laser Doppler flow probe and intracranial pressure monitor were similarly placed. The data were simultaneously processed using multimodality recording monitoring. The monitoring was continued during the post-operative period and totalled over 190 hours. Data were analysed as specific events and as trends. Initial tissue oxygen levels were low but improved in all cases as the intracranial pressure was reduced. This effect was independent of the cerebral perfusion pressure. Laser Doppler flow provided an indicator of compromised brain function and tissue oxygenation an indicator of established ischemia.

Complications of varicose vein surgery.

A retrospective review was carried out of patients who had undergone surgery for varicose veins over an 8 year period between 1985 and 1993. We wished to determine the incidence of various complications so that the risks of surgery could be openly discussed with patients. A total of 973 limbs were operated upon in 599 patients (413 F, 186 M; mean age 49 years). All patients were under the care of a single consultant vascular surgeon who was present at 92% of operations and all patients were reviewed postoperatively. There was no perioperative mortality. Wound complications (haematoma, cellulitis or abscess) occurred in 2.8% of limbs and minor neurological disturbance (numbness or tingling) in 6.6%. Leakage of lymph from the groin occurred in five patients, all of whom had undergone exploration for groin recurrence. Major complications included three cases of deep venous thrombosis (0.5%), one pulmonary embolus, and one foot-drop. There was one major vascular injury, the common femoral vein being damaged in a patient having a third operation on the groin for persistent recurrence. Vein patch repair was performed and patency was maintained. The overall incidence of major complications was 0.8%. Minor complications occurred in 17% of patients. It is unlikely that major complications can be eliminated. In this retrospective review there will be some under-reporting, but we are confident that this is restricted to minor complications.

How much can be concluded from the International Subarachnoid Aneurysm Trial (ISAT)?

Recently published data from the International Subarachnoid Aneurysm Trial (ISAT) shows that for patients enrolled in the trial there is a 7.4% reduction in the incidence of death or dependency at 1 year if they undergo coiling, rather than clipping. Furthermore, extrapolation of longer-term follow-up data for patient mortality appears to suggest that this advantage will be maintained in the longer term. Based on a reassessment of the published data, the authors note: (1) the incidence of rebleeding following treatment is approximately three times higher in the coiled group (p<0.001); (2) the need for aneurysm retreatment is likely to be higher in the coiled group; (3) trends in longer-term mortality data are not a reliable basis for predicting future outcomes of the trial; (4) trends in longer-term morbidity data are more reliable and suggest that the advantage of coiling diminishes with time; (5) The absence of up-to-date published rates of aneurysm retreatment and of longer-term rates of death or dependence makes ISAT extremely hard to interpret. It is far from clear that the early advantage of coiling will be maintained in the future and, hence, longer follow-up is required. Treatment of aneurysms is a continually evolving field and there is currently no other major source of information concerning management of aneurysms. For these reasons the authors recommend the instigation of a national aneurysm registry to prospectively collect data.

Angiography postclipping and coiling of cerebral aneurysms.

Postclipping cerebral angiography is generally not practised in the UK. The International Subarachnoid Trial (ISAT) data show that coiling compared favourably with clipping in the early posttreatment phase. We present a 4-year, single unit experience comparing cerebral angiography at 6 months postclipping and postcoiling, defining the proportion of aneurysms in either group, which were incompletely excluded from the cerebral circulation after treatment. There were 4 'dog-ear' remnants (4.6%) in the clipping group of 86 aneurysms, one of which required further surgery. Thirty-one out of 82 (37.8%) coiled aneurysms that underwent check angiography were inadequately excluded from the cerebral circulation at 6 months. Of these, to date, four patients have undergone re-coiling. Although the immediate complications of coiling may be less than those of clipping (ISAT), it seems that the degree and permanence of exclusion of an aneurysm from the cerebral circulation may be more secure with surgery. In summary, the rates of incomplete aneurysmal exclusion from the cerebral circulation, the requirement for reintervention and the requirement for continuing surveillance were all higher in the coiled population than in the clipped population.

Postoperative subdural empyema caused by Propionibacterium acnes--a report of two cases.

Two patients with postoperative subdural empyema following burr hole evacuation of chronic subdural haematoma are reported, both caused by Propionibacterium acnes. The need to consider this diagnosis in patients developing recurrent symptoms after surgical drainage of chronic subdural haematoma is emphasized.

Vim thalamotomy for the relief of the intention tremor of multiple sclerosis.

We have reviewed the outcome of patients who have undergone thalamotomy for the intention tremor of multiple sclerosis (MS). Twenty-four patients underwent 29 procedures between 1988 and 1995. These patients were assessed for the degree of disability due to MS and for the impairment of arm function due to the tremor. Preoperative, postoperative and last follow-up score (mean 2.2 years) were determined for arm function following thalamotomy. Patient satisfaction, where expressed, was recorded. Twenty-three procedures (79%) resulted in immediate improvement in arm function. Thirteen complications were recorded. Postoperative fatigue was demonstrated after seven procedures. Sustained benefit was seen after 18 procedures (62%). Out of 23 patients whose opinions are recorded four were enthusiastic and 10 satisfied with the outcome. We conclude that, despite severe disability, a majority of patients with intention tremor of MS may still benefit from thalamotomy and are satisfied with the results.

Granular cell tumour of the spinal cord: case report.

A granular cell tumour presenting within the spinal cord of a 17-year-old woman is described. This distinctive tumour has a widespread distribution, but has been reported only rarely in the central nervous system. The literature is reviewed.

Injury rates in Shotokan karate.

OBJECTIVE: To document the injury rate in three British Shotokan karate championships in consecutive years. In these tournaments strict rules governed contact, with only "light" or "touch" contact allowed. Protective padding for the head, hands, or feet was prohibited. METHODS: Prospective recording of injuries resulting from 1770 bouts in three national competitions of 1996, 1997, and 1998. Details of ages and years of karate experience were also obtained. RESULTS: 160 injuries were sustained in 1770 bouts. The overall rate of injury was 0.09 per bout and 0.13 per competitor. 91 (57%) injuries were to the head. The average age of those injured was 22 years, with an average of nine years of experience in karate. CONCLUSIONS: The absence of protective padding does not result in higher injury rates than in most other series of Shotokan karate injuries. Strict refereeing is essential, however, to maintain control and minimise contact.

Biocatalytic synthesis of acrylates in organic solvents and supercritical fluids: III. Does carbon dioxide covalently modify enzymes?

We have previously demonstrated that the activity of the lipase (Candida cylindracea) catalyzed transesterification reaction between methylmethacrylate and 2-ethylhexanol in supercritical carbon dioxide is comparatively low. In this article, we have investigated the same reaction in supercritical carbon dioxide with a special emphasis on determining the extent of any interaction between the enzyme and carbon dioxide. Transesterification reaction rates in hexane and supercritical carbon dioxide are compared at different temperatures. In supercritical carbon dioxide, temperature was found to have no significant effect on reaction rate in the range of 40 degrees to 55 degrees C. Above 55 degrees C, however, the reaction rate increased significantly as a function of temperature. It appears that carbon dioxide forms reversible complexes with the free amine groups on the surface of the enzyme. Direct evidence of modification was obtained using mass spectroscopy to detect the extent of modification of a pure protein. The kinetics of the reaction have been studied in hexane, and they obey a ping-pong bi-bi mechanism with inhibition by 2-ethylhexanol. The effect of bubbling carbon dioxide and/or fluoroform on the reaction rate in hexane at different temperatures suggests that the enzyme undergoes shear inactivation in hexane. (c) 1995 John Wiley & Sons, Inc.

Fragmentation of complex carbohydrates following ionization by matrix-assisted laser desorption with an instrument fitted with time-lag focusing.

Matrix-assisted laser desorption/ionization time-of-flight spectra of carbohydrates recorded with an instrument using time-lag focusing (delayed extraction) were found to exhibit fragment ions, whereas, in the non time-lag-focusing mode, fragment ions were not observed. Fragment ions consisted both of glycosidic and cross-ring cleavage products whose absolute, but not relative abundance increased with the delay time and indicated that they were formed within the ion source. Only the glycosidic cleavage ions were present in post-source decay spectra and their abundance was inversely correlated with the delay time. The results indicated that the cross-ring cleavages were predominately the products of fast reactions whereas the glycosidic cleavages occurred over a longer time frame.

Comparison of fragmentation modes for the structural determination of complex oligosaccharides ionized by matrix-assisted laser desorption/ionization mass spectrometry.

Fragment ions from underivatized N-linked oligosaccharides ionized by matrix-assisted laser desorption/ionization mass spectrometry were obtained by spontaneous fragmentation on a magnetic sector mass spectrometer, by post-source decay (PSD) on a reflectron time-of-flight (TOF) instrument and by collision-induced dissociation on a magnetic sector instrument fitted with an orthagonal-TOF analyser. Spontaneous fragmentation on the magnetic sector instrument produced ions mainly by glycosidic cleavage together with two abundant ions formed by cross-ring cleavage of the reducing-terminal residue. The PSD spectra were similar, the majority of ions being formed by glycosidic cleavage. Internal fragment ions were abundant. High-energy collision-induced dissociation spectra recorded with the orthagonal-TOF analyser, differed considerably from the other types of spectra, particularly in the appearance of major fragment ions produced by cross-ring cleavages of most of the constituent monosaccharide residues. These ions allowed much sequence and branching information to be obtained from the oligosaccharide.