Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

BACKGROUND:Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. CONCLUSION: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) is a minimal invasive method to produce thermonecrosis in cerebral tumour tissue. Clinical data are sparse due to its limited application until now and the value of this approach for tumour control and survival time remain to be defined. Twenty-four patients (7 low-grade gliomas, 11 anaplastic gliomas, 6 glioblastomas) with brain tumours, most recurrences, were treated with SLITT, in total 30 laser procedures were performed. Under local anaesthesia a 600 micro m laser-fiber was inserted by the stereotactic-guided technique. In open low-field MR the denaturation of the tumour by a Nd-YAG-laser (1064 nm) was monitored using T 1 -weighted 3-D turbo FLASH sequences. The ablation procedure had to be stopped twice because of neurological deficit, one major infection occurred. In two cases neurological improvement was observed. Mean survival times for low grade astrocytomas, anaplastic gliomas and glioblastomas were 144 months, 39 months, 17 months, respectively. Mean survival times after SLITT were 34 months, 30 months and 9 months, respectively. Mean times to progression after SLITT for the 3 histological subgroups were 16 months, 10 months and 4 months, respectively. Five patients with low grade astrocytoma and a KI greater or equal 70 maintained a high quality functional status for 11, 20, 21, 33 and 43 months. In anaplastic tumours patients maintained a KI of 70 for a median time of 15 months and for those with glioblastoma the respective high quality duration was 7.5 months after SLITT. SLITT for selected patients with glioma could have a clinical value in a multimodality treatment schedule maintaining quality of live. Due to the minimal invasive technique, the method is a therapy of choice and may be favoured to reoperation. Major indications of this treatment are small tumours, in eloquent regions and deep seated, as well as in older patients or patients in poor functional status.

The purpose of this study was to achieve a more radical resection of tumors in the area of the motor cortex via minimal craniotomy using a combination of neuronavigation and neurophysiological monitoring with direct electrical cortical stimulation and to compare retrospectively the clinical outcome and postoperative magnetic resonance imaging with a control group that was operated on in our service when the combination of these monitoring techniques was not available. A total of 42 patients with tumors in or near the central region underwent surgery with neuronavigation guidance and neurophysiological monitoring. The primary motor cortex was identified intraoperatively by the somatosensory evoked phase reversal method and direct cortical stimulation. The functional areas were transferred into the neuronavigation system. By stimulating the identified primary motor cortex and displaying the motor area in the operating microscope a permanent control of the motor function was possible during the whole operation. Using these techniques a more radical tumor resection - evaluated by postoperative MRI - was achieved in the study group (p = 0.04) and also a trend toward a better neurological outcome.