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

Extracellular matrix (ECM) alterations in the central nervous system (CNS) of multiple sclerosis (MS) patients result from blood-brain barrier breakdown, release and activation of proteases, and synthesis of ECM components. To elucidate their potential pathophysiologic roles, we analyzed expression of major CNS ECM proteoglycans (PGs) in MS and control CNS tissues. In active MS plaque edges, 3 CNS lecticans (versican, aggrecan, and neurocan) and dermatan sulfate PG were increased in association with astrocytosis; in active plaque centers they were decreased in the ECM and accumulated in foamy macrophages, suggesting that these ECM PGs are injured and phagocytosed along with myelin. In inactive lesions they were diminished and in normal-appearing white matter they showed heretofore-unappreciated abnormal heterogeneous aggregation. Phosphacan, an ECM PG abundant in both gray and white matter, was less markedly altered. Since in development the spaciotemporal expression of ECM PGs influences neurite outgrowth, cell migration, axon guidance, and myelination, these data suggest that 1) enhanced white matter lectican and dermatan sulfate PG expression in the pro-inflammatory milieu of expanding lesion edges contributes to their sharp boundaries and the failure of neuronal ingrowth; 2) decreases in plaque centers may preclude regeneration and repair; and 3) diffuse ECM PG damage relates to axon degeneration outside of overt lesions. Thus, ECM PG alterations are specific, temporally dynamic, and widespread in MS patients and may play critical roles in lesion pathogenesis and CNS dysfunction.

Over the past decade, electrocorticography (ECoG) has been used for a wide set of clinical and experimental applications. Recently, there have been efforts in the clinic to adapt traditional ECoG arrays to include smaller recording contacts and spacing. These devices, which may be collectively called “micro-ECoG” arrays, are loosely defined as intercranial devices that record brain electrical activity on the submillimeter scale. An extensible 3D-platform of thin film flexible micro-scale ECoG arrays appropriate for Brain-Computer Interface (BCI) application, as well as monitoring epileptic activity, is presented. The designs utilize flexible film electrodes to keep the array in place without applying significant pressure to the brain and to enable radial subcranial deployment of multiple electrodes from a single craniotomy. Deployment techniques were tested in non-human primates, and stimulus-evoked activity and spontaneous epileptic activity were recorded. Further tests in BCI and epilepsy applications will make the electrode platform ready for initial human testing.

Object Blood blister–like aneurysms (BBAs) arise from the supraclinoid internal carotid artery (ICA) at non-branching sites. These aneurysms are challenging to treat primarily with either surgical clip placement or endovascular therapy. The authors describe a series of 4 patients who presented with high-grade subarachnoid hemorrhage (SAH) due to a BBA, which was treated with an extracranial–intracranial (EC–IC) bypass followed by trapping of the aneurysm. Methods Four patients presented with SAH due to a BBA of the ICA. Three of these patients were treated with an endovascular procedure; following the vasospasm period, definitive treatment with EC–IC bypass followed by trapping of the aneurysmal parent vessel was performed. Results Two of the patients who were treated endovascularly suffered rebleeding prior to bypass and trapping. Three of the 4 patients had a good outcome (modified Rankin Scale Score 1 or 2), and 1 patient who suffered 2 episodes of rebleeding died. Conclusions Treatment of BBAs of the ICA remains difficult, particularly in the setting of high-grade SAH. Patients with this challenging condition often require multiple procedures and have a high incidence of rebleeding. Definitive treatment of these aneurysms consists of EC–IC bypass and surgical or endovascular trapping.

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.

Obsessive-compulsive disorder (OCD) is a common, chronic, disabling anxiety disorder characterized by recurrent obsessive thoughts and uncontrolled repetitive acts. Although many patients respond to various pharmacological treatments, there is a cohort of patients with intractable or refractory disease. The authors present the case of a patient with intractable OCD who was treated with bilateral electrical stimulators, which were stereotactically placed in the anterior limbs of the internal capsules. Following psychiatric consultation and 10 years of empirical medication regimens for OCD, a woman was referred for neurosurgical evaluation. After informed consent had been obtained from the patient, the authors placed bilateral stimulator leads in the anterior limbs of the internal capsules. The stereotactic coordinates were based on data in pertinent current literature. The stimulation parameters, which are presented in this paper, were set at 2 weeks and reviewed at 6 weeks and 3 months postoperatively. No changes were required. Postoperative analysis included evaluation by the patient's referring psychiatrist, a second independent psychiatrist, and pre- and postoperative administration of the Yale-Brown Obsessive Compulsive Scale. A marked improvement was noted in thispatient's OCD symptomatology and general psychosocial function. Previous documentation of patient responses to psychosurgical procedures for intractable or refractory OCD has been met with little enthusiasm, presumably because of the invasiveness and irreversibility of the surgery. In this report the authors suggest that deep brain stimulation of appropriate targets may be an effective and safe treatment for certain patients with OCD and a potentially reversible treatment for those patients who do not obtain therapeutic benefit.

Object The angioarchitectural features of an AVM provide key information regarding natural history and treatment planning. Because of rapid filling and vascular overlap, 2D and 3D-DSA are often suboptimal for evaluation of these features. We have developed an algorithm that derives a series of fully time resolved 3D-DSA volumes (4D-DSA) at up to 30frames/sec from a conventional 3D-DSA. The temporal/spatial resolution of 4D reconstructions is significantly higher than that provided by current MRA and CTA techniques. 4D reconstruction allows viewing of an AVM from any angle at any time during its opacification. This feasibility study investigated the potential of 4DDSA to improve the ability to analyze angioarchitectural features as compared to conventional 2D and 3D-DSA. Methods 2D, 3D and 4D-DSA reconstructions of angiographic studies of 6 AVMs were evaluated by 3 cerebrovascular neurosurgeons and 1 interventional neuroradiologist. These observers evaluated the ability of each modality to visualize the angioarchitectural features of the AVMs. They also compared the information provided using the combination of 2D and 3D-DSA with that provided by a 4D-DSA reconstruction. Results By consensus, 4D-DSA provided the best ability to visualize the internal features of the AVM including intranidal aneurysms, fistula, venous obstructions and sequence of filling and draining. 2D and 3D images in comparison were limited because of overlap of the vasculature. Conclusion In this small series 4D-DSA provided better ability to visualize an AVM’s angioarchitecture than did conventional methods. Further experience is required to determine the ultimate utility of this technique.

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