Characteristics associated with outcome in patients with first-ever posterior fossa stroke.

BACKGROUND AND PURPOSE: Factors such as infarct volume, infarct location and symptom severity can considerably influence long-term outcome in posterior fossa strokes. The decision about therapy can sometimes be complicated by discrepancies between infarct volume and clinical severity. We aimed to evaluate imaging and clinical parameters possibly influencing long-term outcome in patients with first-ever posterior fossa stroke. METHODS: Imaging was performed on a 3-T magnetic resonance imaging scanner. Sixty-one of 1795 patients from the observational 1000Plus and LOBI studies (NCT00715533 and NCT02077582, clinicaltrials.org) were enrolled, meeting the inclusion criteria of first-ever posterior fossa stroke and magnetic resonance imaging examination within 24 h after symptom onset. Infarcts were classified as belonging to a proximal, middle or distal territory location in the posterior fossa. Good outcome was defined as a modified Rankin scale score of ≤1 at 3 months. RESULTS: The largest lesion volumes on diffusion-weighted imaging on day 0 and fluid attenuation inversion recovery (FLAIR) on day 6 were found in the middle territory location with a median volume of 0.4 mL on diffusion-weighted imaging and 1.0 mL on FLAIR on day 6 versus 0.1/0.3 mL in the proximal and 0.1/0.1 mL in the distal territory location of the posterior fossa, respectively. Parameters associated with poor outcome were older age (P = 0.005), higher National Institutes of Health Stroke Scale score on admission/discharge (P = 0.016; P = 0.001), larger lesion volumes on FLAIR on day 6 (P = 0.013) and dysphagia (P = 0.02). There was no significant association between infarct location and modified Rankin scale score on day 90. CONCLUSION: Infarct volume and clinical severity, but not infarct location, were the main contributors to poor long-term outcome in first-ever posterior fossa strokes.

Matrix metalloproteinases in human spontaneous intracerebral hemorrhage: an update.

BACKGROUND: In default of a plausible and satisfactory causal treatment for hemorrhagic stroke, a role of matrix metalloproteinases (MMPs) in the pathogenesis of cerebrovascular diseases has recently been widely discussed. The well-known impact of MMPs on extracellular matrix destruction triggered by inflammation as a foundation for several diseases, including stroke, is very much in evidence. Newly, some additional aspects of MMP function considering their intracellular activity crucial for neuronal death following ischemic brain damage have emerged. The effect of blood-brain barrier disruption caused by MMPs on the prognosis in patients suffering from spontaneous intracerebral hemorrhage (ICH) has been of interest since it throws a new light upon the pathogenesis, course and possible therapeutic approaches for this least treatable and at the same time most life-threatening form of stroke. Hence, we primarily aimed to review the current clinical knowledge on the significance of metalloproteinase activation in the course of spontaneous intracranial hemorrhage in humans. We also provide a brief characterization of the MMP enzyme family and report on the latest findings on issues arising from experimental studies. METHODS: A Medline search using the following key words was performed: matrix metalloproteinases + spontaneous intracerebral hemorrhage/intracranial hemorrhage/bleeding/hemorrhagic stroke. We accepted studies reporting on MMP expression in adult patients with spontaneous ICH, as well as its relation to radiological and clinical features and patients' outcome. For the final review, 18 clinical studies were considered. MMP inhibition was reviewed on the basis of 11 relevant experimental studies. Also, some relevant reports on the biology of MMPs and their pathophysiology in ICH were reviewed. RESULTS AND CONCLUSIONS: Many studies provide convincing evidence of a detrimental role of MMPs in ICH, stressing their association with neuroinflammation. The role of MMPs in hemorrhagic stroke appears critical for hematoma and brain edema growth as well as for neuronal death, which are understood as secondary brain injury and may have a considerable clinical impact. Although data on human spontaneous ICH are scarce and mostly based on small populations, they reveal the apparent correlation between MMPs and clinical and radiological ICH features as well as the functional outcome, which might rationalize future therapeutic strategies. However, attempts at MMP inhibition in spontaneous ICH have solely been made under experimental conditions and were associated with a wide range of possible side effects. Therefore, further comprehensive, elucidating investigations in this field are vital before any conclusions could be translated to humans.