Volume reduction with surgery for ICH: when is it effective? Analysis of the CT scans from the STICH II trial.

BACKGROUND: The surgical trial of lobar intracerebral haemorrhage (STICH II) was a randomised controlled trial evaluating early surgical removal of a clot. This paper investigates volume change in both arms of the trial with respect to Extended Glasgow Outcome Scale (GOSE) groups. METHODS: Patients randomised into STICH II had an initial diagnostic CT and a second CT 5 days after randomisation. Each scan was anonymously assessed by at least two central readers. An analysis of agreement between the two readers was conducted using kappa tests and intraclass correlation. The change in volume in both the early surgery (ES) and the initial conservative treatment (ICT) arms were analysed with respect to the six-month GOSE outcome. RESULTS: Of the 597 patients randomised in the trial there were 582 pre-randomisation scans and 566 5-day scans available for analysis of agreement. There was good agreement between the assessors for the radiological inclusion criteria including volume (ICC = 0.87) and this was better than the agreement between the assessor and local investigator (ICC = 0.73). There were 526 patients with two scans available for analysis of change in volume measurement. The median percentage change in volume for the ES group was a reduction of 92.4% (IQR 75.6%, 99.0%) while for the ICT group, in which some cases crossed over to delayed surgery, it was only 5.7% (IQR 16.4% increase, 29.5% reduction). ES patients with almost complete removal (99-100%) had the best outcome with only 30% dead or lower severely disabled. For the ICT group outcome was related to the final volume: the smaller the final volume the better the outcome. CONCLUSIONS: This analysis provides evidence for central assessments of scans in exploratory analyses and further information regarding the potential advantage of early and more complete clot removal on outcome in ICH and should inform the planning of future trials.Clinical trials registration: ISRCTN22153967.

Five-year results of randomized bioactive versus bare metal coils in the treatment of intracranial aneurysms: the Matrix and Platinum Science (MAPS) Trial.

BACKGROUND: No randomized trial of intracranial aneurysm coiling has compared long-term efficacy of polymer-modified coils to bare metal coils (BMCs). We report 5-year results comparing Matrix2 coils to BMCs. The primary objective was to compare the rates of target aneurysm recurrence (TAR) at 12 months. Secondary objectives included angiographic outcomes at TAR or 12 months and TAR at 5 years. METHODS: A total of 626 patients were randomized to BMCs or Matrix2 coils. Detailed methods and 1-year results have been published previously. RESULTS: Of 580 patients eligible for 5-year follow-up, 431 (74.3%) completed follow-up or reached TAR. Matrix2 coils were non-inferior to BMCs (P=0.8) but did not confer any benefit. Core lab reported post-treatment residual aneurysm filling (Raymond III) correlated with TAR (P<0.0001) and with aneurysm hemorrhage after treatment (P<0.008). Repeat aneurysmal hemorrhage after treatment, but before hospital discharge, occurred in three patients treated for acutely ruptured aneurysms. Additionally, two patients treated for unruptured aneurysms experienced a first hemorrhage during follow-up. All five hemorrhages resulted from aneurysms with Raymond III residual aneurysm filling persisting after initial treatment. After 5 years follow-up, 2/626 (0.3%) patients are known to have had target aneurysm rupture following hospital discharge. The annualized rate of delayed hemorrhage after coiling was 2/398/5=0.001 (0.1%) per year for unruptured aneurysms and 0 for ruptured aneurysms. CONCLUSIONS: After 5 years Matrix2 coils were non-inferior to BMCs but no benefit was demonstrated. Post-treatment residual angiographic aneurysm filling (Raymond III) is strongly associated with TAR (P<0.0001) and post-treatment aneurysmal hemorrhage (P=0.008).

Multimodality treatment of cerebral arteriovenous malformations.

BACKGROUND: Many arteriovenous malformations (AVMs) can be treated with one modality, but with increasing complexity a combination of techniques, including surgical excision, embolization, and radiosurgery, may be beneficial. The 2 senior authors' experience in the multimodal management of AVMs from 1980-2008 is reported, including the results in all patients with rehemorrhage while awaiting treatment or after partial initial treatment has begun. The series contains a disproportionately high number of Spetzler-Martin grade IV and V lesions, owing to the nature of the referral practice. METHODS: Data were collected prospectively. Only patients who were managed until treatment options were exhausted were included; this entailed either treatment to the point of AVM obliteration or inability to treat further using any or all modalities. Patients who presented with intracranial hemorrhage (ICH) in extremis in whom the AVM was excised during the first operation were also included. RESULTS: Of the 290 patients, 265 underwent treatment, and 25 were managed conservatively. An unruptured AVM was present in 48% of patients. Cure was achieved in 233 (88%) of treated patients. Cure was achieved in 25 of 37 patients undergoing radiosurgery only, 56 of 57 undergoing surgery, 100 of 101 undergoing embolization and microsurgical excision, 20 of 34 undergoing embolization alone, 12 of 17 undergoing embolization and radiosurgery, 5 of 5 undergoing surgery and radiosurgery, and 14 of 14 patients undergoing all 3 modalities. Spetzler-Martin grade was found to correlate negatively with cure (P < 0.001). There was a good outcome in 210 patients (72%), moderate disability in 40 patients (14%), severe disability in 22 patients (8%), vegetative state in 1 patient, and 17 patients (6%) died. There was a favorable outcome (no or only moderate deficits) in 93% of patients with Spetzler-Martin grade I-III lesions. The outcome was favorable in 13 of 25 patients (52%) having no treatment, 32 of 37 (86%) having radiosurgery only, 30 of 34 (88%) having embolization only, 54 of 57 (95%) having surgery only, 87 of 101 (86%) having embolization and surgery, 16 of 17 (94%) having embolization and radiosurgery, 5 of 5 (100%) having surgery and radiosurgery, and 13 of 14 (93%) having all 3 modalities. These outcomes included morbidity from initial presenting symptoms, from treatment, and from rehemorrhage. Good recovery was more likely in patients who were treated with surgery as one of the treatments (P = .025). Considering only new deficits related to treatment, 9 patients (3%) incurred severe neurologic deficits, 11 patents died after treatment, 2 patients died of postoperative hematomas, and 6 died of rehemorrhage from residual AVM. Increasing age, Spetzler-Martin grade, and rehemorrhage were correlated with a poorer Glasgow Outcome Scale score (P < 0.05). CONCLUSIONS: These data suggest a higher risk of hemorrhage after partial obliteration of AVM. One should ascertain an acceptably high likelihood of complete obliteration before embarking on treatment. Using a multimodality approach, the authors were able to cure 92% of treated Spetzler-Martin grade I-IV lesions but only 53% of treated Spetzler-Martin grade V lesions. A major neurologic deficit, disabling to the patient, was incurred in 3% of cases, and 11 patients died.

Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial.

BACKGROUND: The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10-100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients. METHODS: In this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967. FINDINGS: 307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI -4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367). INTERPRETATION: The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage. FUNDING: UK Medical Research Council.

Update on the Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II): statistical analysis plan.

BACKGROUND: Previous studies had suggested that the outcome for patients with spontaneous lobar intracerebral haemorrhage (ICH) and no intraventricular haemorrhage (IVH) might be improved with early evacuation of the haematoma. The Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) set out to establish whether a policy of earlier surgical evacuation of the haematoma in selected patients with spontaneous lobar ICH would improve outcome compared to a policy of initial conservative treatment. It is an international, multi-centre, prospective randomised parallel group trial of early surgery in patients with spontaneous lobar ICH. Outcome is measured at six months via a postal questionnaire. RESULTS: Recruitment to the study began on 27 November 2006 and closed on 15 August 2012 by which time 601 patients had been recruited. The protocol was published in Trials (http://www.trialsjournal.com/content/12/1/124/). This update presents the analysis plan for the study without reference to the unblinded data. The trial data will not be unblinded until after follow-up is completed in early 2013. The main trial results will be presented in spring 2013 with the aim to publish in a peer-reviewed journal at the same time. CONCLUSION: The data from the trial will provide evidence on the benefits and risks of early surgery in patients with lobar ICH. TRIAL REGISTRATION: ISRCTN: ISRCTN22153967.

Surgical trial in lobar intracerebral haemorrhage (STICH II) protocol.

BACKGROUND: Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively. There is equipoise about the management of patients between these two extremes. In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation. The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment. METHODS/DESIGN: An international multicentre randomised parallel group trial. Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible. All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage (≤1 cm from the cortex surface of the brain and 10-100 ml in volume). Any clotting or coagulation problems must be corrected and randomisation must take place within 48 hours of ictus. With 600 patients, the study will be able to demonstrate a 12% benefit from surgery (2p < 0.05) with 80% power.Stratified randomisation is undertaken using a central 24 hour randomisation service accessed by telephone or web. Patients randomised to early surgery should have the operation within 12 hours. Information about the status (Glasgow Coma Score and focal signs) of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days (+/- 2 days). Outcome is measured at six months via a postal questionnaire to the patient. Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale. Secondary outcomes include: Mortality, Rankin, Barthel, EuroQol, and Survival. TRIAL REGISTRATION: ISRCTN: ISRCTN22153967.

Aneurysmal subarachnoid hemorrhage: management strategies and clinical outcomes in a regional neuroscience center.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) affects six to eight people per 100,000 annually, yet the optimum management of this condition remains controversial. Although the International Subarachnoid Aneurysm Trial (ISAT) explored this area, only 28% of patients from our center were randomized in that study. Our purpose was to evaluate the treatment and outcomes of patients not recruited into ISAT. METHODS: Procedural data, adverse events, additional procedures, and length of hospital stay were recorded for 122 patients who came to our center with aneurysmal SAH. Modified Rankin Scale (MRS) was assessed at 2 months and at 1 year by a postal questionnaire and telephone interview. RESULTS: Nine patients were treated conservatively, 67 underwent surgical clipping, and 46 underwent endovascular therapy. At 2 months, a good grade (MRS 0-2) was achieved in 67% of patients treated with endovascular therapy and in 45% of patients treated with surgery. At 1 year, a good grade was achieved in 72% in the endovascular group and 49% in the surgical group. CONCLUSION: Endovascular therapy was a safe and effective treatment in a series of subjects who were not randomized in ISAT and in whom endovascular therapy was chosen over surgical clipping. The outcomes at 2 months and 1 year for those subjects treated with endovascular therapy were superior to the outcomes in those treated with surgical clipping. Our study was small and from a single center, but in this population the outcomes of endovascular treatment were similar to those reported by ISAT.

Unruptured intracranial aneurysms: benign curiosity or ticking bomb?

15 years ago, the treatment of incidentally discovered intracranial aneurysms was straightforward with a good evidence base behind it. When intracranial aneurysms were identified, people were referred to neurosurgeons who would offer surgical repair if the patient was in reasonable health and had a good life expectancy. Since that time, several studies have given contradictory evidence for what should be done with these lesions, and a new technique for the repair of aneurysms, endovascular coil embolisation, has been developed. Here we review the research and make several recommendations. First, incidentally discovered aneurysms in the anterior circulation less than 7 mm in size in people with no personal or family history of subarachnoid haemorrhage should be left untreated. Second, people with remaining life expectancy of less than 20 years or so (ie, those over age 60 years) should be informed that from a statistical point of view the benefits of treatment do not outweigh the risks. Third, in all other cases treatment with surgical clipping or coil embolisation should be advised. And finally, if surgical treatment is not feasible then medical hypotensive treatment may be a viable alternative.