Outcome of intravenous thrombolysis in stroke patients weighing over 100 kg.

BACKGROUND: Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. METHODS: Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0-2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. RESULTS: Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). CONCLUSION: Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families.

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed.

Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients.

BACKGROUND: No randomized study has yet compared efficacy and safety of aspirin and anticoagulants in patients with spontaneous dissection of the cervical carotid artery (sICAD). METHODS: Prospectively collected data from 298 consecutive patients with sICAD (56% men; mean age 46 +/- 10 years) treated with anticoagulants alone (n = 202) or aspirin alone (n = 96) were retrospectively analyzed. Admission diagnosis was ischemic stroke in 165, TIA in 37, retinal ischemia in 8, and local symptoms and signs (headache, neck pain, Horner syndrome, cranial nerve palsy) in 80 patients, while 8 patients were asymptomatic. Clinical follow-up was obtained after 3 months by neurologic examination (97% of patients) or structured telephone interview. Outcome measures were 1) new cerebral ischemic events, defined as ischemic stroke, TIA, or retinal ischemia, 2) symptomatic intracranial hemorrhage, and 3) major extracranial bleeding. RESULTS: During follow-up, ischemic events were rare (ischemic stroke, 0.3%; TIA, 3.4%; retinal ischemia, 1%); their frequency did not significantly differ between patients treated with anticoagulants (5.9%) and those treated with aspirin (2.1%). The same was true for hemorrhagic adverse events (anticoagulants, 2%; aspirin, 1%). New ischemic events were significantly more frequent in patients with ischemic events at onset (6.2%) than in patients with local symptoms or asymptomatic patients (1.1%). CONCLUSIONS: Within the limitations of a nonrandomized study, our data suggest that frequency of new cerebral and retinal ischemic events in patients with spontaneous dissection of the cervical carotid artery is low and probably independent of the type of antithrombotic treatment (aspirin or anticoagulants).

Intravenous thrombolysis in stroke patients with hyperdense middle cerebral artery sign.

BACKGROUND AND PURPOSE: We assessed the safety and efficacy of intravenous thrombolysis (IVT) in acute stroke patients with hyperdense middle cerebral artery sign (HMCAS). PATIENTS AND METHODS: Data from consecutive patients with acute (within 6 h of symptom onset) ischaemic stroke admitted between January 1999 and November 2007, in whom HMCAS was diagnosed on admission CT scan was retrospectively analysed. Seventy-one patients, admitted within the 3-h window, were treated with IVT, whilst further 42, admitted 3-6 h after symptom onset, were not. At 3-month clinical follow-up, outcome, mortality at 3 months and incidence of symptomatic intracranial haemorrhage were evaluated. RESULTS: The two groups were comparable concerning age, stroke risk factors, prior antithrombotic treatment and NIHSS scores on admission. Good outcome (mRS score

Gender differences in spontaneous cervical artery dissection.

We analyzed sex differences in 696 patients with spontaneous cervical artery dissection. There were more men (n = 399; p < 0.0001), and men showed a higher frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/- 9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18 vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p = 0.001). Outcome and mortality were similar in both sexes.

Seasonal variability in spontaneous cervical artery dissection.

We examined the seasonal variability of spontaneous cervical artery dissection (sCAD) by analysing prospectively collected data from 352 patients with 380 sCAD (361 symptomatic sCAD; 305 carotid and 75 vertebral artery dissections) admitted to two university hospitals with a catchment area of 2,200,000 inhabitants between 1985 and 2004. Presenting symptoms and signs of the 380 sCAD were ischaemic stroke in 241 (63%), transient ischaemic attack in 40 (11%), retinal ischemia in seven (2%), and non-ischaemic in 73 (19%) cases; 19 (5%) were asymptomatic sCAD. A seasonal pattern, with higher frequency of sCAD in winter (31.3%; 95% confidence interval (CI): 26.5 to 36.4; p=0.021) compared to spring (25.5%; 95% CI: 21.1 to 30.3), summer (23.5%; 95% CI: 19.3 to 28.3), and autumn (19.7%; 95% CI: 15.7 to 24.1) was observed. Although the cause of seasonality in sCAD is unclear, the winter peaks of infection, hypertension, and aortic dissection suggest common underlying mechanisms.

Thrombolysis in stroke patients aged 80 years and older: Swiss survey of IV thrombolysis.

This databank-based, multicenter study compared all stroke patients with IV tissue plasminogen activator aged > or = 80 years (n = 38) and those < 80 years old (n = 287). Three-month mortality was higher in older patients. Favorable outcome (modified Rankin scale < or = 1) and intracranial hemorrhage (asymptomatic/symptomatic/fatal) were similarly frequent in both groups. Logistic regression showed that stroke severity, time to thrombolysis, glucose level, and history of coronary heart disease independently predicted outcome, whereas age did not.

IV thrombolysis in patients with acute stroke due to spontaneous carotid dissection.

The authors reviewed the histories of 33 patients (ages 44 to 50 years) treated with IV thrombolysis for acute stroke due to spontaneous cervical carotid artery dissection. Median NIH Stroke Scale (NIHSS) score on admission was 15. No new or worsened local signs, subarachnoid hemorrhage, pseudoaneurysm formation, or rupture of the cervical ICA were observed. At 3 months, median NIHSS was 7 and median modified Rankin Scale (mRS) 2.5; mRS < or = 2 was observed in 17 patients.

Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs.

Despite a deep knowledge on the 3D-structure of several catalytic domains of MMPs, the development of highly specific synthetic active-site-directed inhibitors of MMPs, able to differentiate the different members of this protease family, remains a strong challenge. Due to the flexible nature of MMP active-site, the development of specific MMP inhibitors will need to combine sophisticated theoretical and experimental approaches to decipher in each MMP the specific structural and dynamic features that can be exploited to obtain the desired selectivity.

Clinical significance of detection of multiple acute brain infarcts on diffusion weighted magnetic resonance imaging.

BACKGROUND: Detection of multiple acute brain infarcts (MABI) by diffusion weighted magnetic resonance imaging (DWI) may provide information about stroke mechanism in (1) acute lacunar stroke, where evidence of MABI suggests a cause other than small artery disease (SAD), such as embolism or vasculitis (type 1 MABI); or (2) acute non-lacunar stroke, where MABI in the territory of at least two of the aortic branches supplying the brain indicates the presence of aortic or cardiac embolism rather than artery to artery embolism (type 2 MABI). OBJECTIVE: To evaluate the prevalence of MABI and their impact on aetiological classification and prevention of stroke in patients with acute ischaemic stroke examined with DWI. METHODS: 182 consecutive patients defined by DWI were evaluated. Stroke aetiology was classified according to the TOAST criteria, though "lacunar stroke" included patients with possible aetiologies other than SAD. RESULTS: Type 1 MABI were detected in 21/72 patients (29%) with lacunar stroke, and type 2 MABI in 8/110 (7%) with non-lacunar stroke. A possible stroke mechanism different from SAD was found in nine type 1 MABI cases (43%): cardiac embolism (4); other determined aetiology (3); aortic embolism (2). Cardiac (2) or aortic (1) sources of embolism were detected in eight type 2 MABI cases. MABI patients with cardiac or aortic sources of embolism were treated with warfarin, the remainder with aspirin. CONCLUSIONS: Detection of type 1 MABI in patients with lacunar stroke improved diagnostic confidence and the choice of antithrombotic treatment. Further study is needed on stroke prevention in MABI cases caused by SAD alone.

[Antithrombotic therapy in patients with first-ever stroke and known non-rheumatic atrial fibrillation]. / Antithrombotische Therapie bei Patienten mit erstmaligem Schlaganfall und bekanntem nicht-rheumatischen Vorhofflimmern.

Patients with non-rheumatic atrial fibrillation (AF) have an increased risk for ischemic stroke. The presence of risk factors such as a history of ischemic stroke, transient ischemic attack, diabetes mellitus, arterial hypertension or advanced age allows the classification of patients with AF in three groups with high, moderate, and low stroke risk. High-risk patients should receive oral anticoagulants, low-risk patients aspirin, and moderate-risk patients one of both antithrombotic agents. However, primary stroke prevention studies suggest that many high-risk patients are not anticoagulated, whereas low risk patients receive anticoagulants instead of aspirin. Our retrospective analysis of prospectively collected data examined the antithrombotic therapy of patients with first-ever stroke and known non-valvular AF and compared the results with the recommendations of the Atrial Fibrillation Investigators (AFI) and the Stroke Prevention in Atrial Fibrillation (SPAF) study. Contraindications against anticoagulation were taken into consideration. High-risk patients received in 36% an appropriate antithrombotic therapy according to the AFI-guidelines, and in 28% according to the SPAF-guidelines. About one quarter of low-risk patients were anticoagulated unnecessarily. Our study confirms that many patients with AF and high stroke risk do not get the appropriate antithrombotic therapy, while some patients with low-risk are anticoagulated without cause.

Ischaemic stroke in young adults: predictors of outcome and recurrence.

BACKGROUND: There is limited information about predictors of outcome and recurrence of ischaemic stroke affecting young adults. OBJECTIVE: To assess the predictive value of the presenting characteristics for both outcome and recurrence in young stroke victims. METHODS: Clinical and radiological data for 203 patients aged 16 to 45 years were collected prospectively; they comprised 11% of 1809 consecutive patients with ischaemic stroke. The National Institutes of Health stroke scale (NIHSS), the Bamford criteria, and the trial of ORG 10172 in acute stroke treatment (TOAST) classification were used to define stroke severity, subtype, and aetiology. The clinical outcome of 198 patients (98%) was assessed using the modified Rankin scale (mRS) and categorised as favourable (score 0-1) or unfavourable (score 2-6). RESULTS: Stroke was caused by atherosclerotic large artery disease in 4%, cardioembolism in 24%, small vessel disease in 9%, another determined aetiology in 30%, and undetermined aetiology in 33%. Clinical outcome at three months was favourable in 68%, unfavourable in 29%, and lethal in 3%. Thirteen non-fatal stroke, two fatal strokes, and six transient ischaemic attacks (TIA) occurred during a mean (SD) follow up of 26 (17) months. High NIHSS score, total anterior circulation stroke, and diabetes mellitus were independent predictors of unfavourable outcome or death (p<0.0001, p = 0.011, and p = 0.023). History of TIA predicted stroke recurrence (p = 0.02). CONCLUSIONS: Severe neurological deficits at presentation, total anterior circulation stroke, and diabetes mellitus predict unfavourable outcome. Previous TIA are associated with increased risk of recurrence.

Hypothermia in Acute Stroke.

Moderate hypothermia (MH) is neuroprotective in animal models of focal ischemia when it is induced during, or within few hours after, onset of ischemia. In patients with acute stroke, several observational studies suggested normothermia or mild hypothermia as independent prognostic factors for favorable outcome. Currently, mild hypothermia was only examined in one clinical study that showed its feasibility and safety, but was not powered to examine efficacy. Limited clinical data on MH in humans suggest that this treatment probably reduces mortality in patients with malignant middle cerebral artery infarction. Still, MH in humans is associated with several side effects, intensive medical treatment, and a prolonged stay in the neurologic intensive care unit. Use of MH should be limited to specialized units, applying this treatment within research protocols or observational studies.

Thrombolysis in cervical artery dissection.

Safety and efficacy of intravenous (IVT) and intra-arterial thrombolysis (LIT) in patients with acute stroke due to spontaneous cervical artery dissection were not assessed in any controlled randomized trial. Data on IVT are derived from 4 studies with a total of 50 patients aged 48 +/- 10 years with internal carotid artery dissection. No new or worsened local signs on the side of dissection, such as Horner syndrome and cranial nerve palsy, and no rupture of the cervical carotid artery or subarachnoid hemorrhage (SAH) were observed. One patient dramatically deteriorated during IVT, probably due to arterial embolism arising from a thrombus dislocated from the dissection site. Mortality was 8%, while 40% of patients had a good outcome defined by a modified Rankin scale (mRS) score of 0-2 points. Up to date, a total of 15 patients with carotid or vertebral artery dissection treated with LIT were described. No intracranial hemorrhage, rupture of the dissected vessel, SAH, or recurrent arterial embolism were reported in any patient. Mortality was 13%, while good outcome (mRS score 0-2 points) was observed in 60% of patients, which is comparable to the results in the active group of the PROACT II study. Currently available data thus suggest that IVT should not be withheld in patients with acute stroke due to cervical artery dissection. LIT treatment can only be based on individual decision-making.

Prognosis of asymptomatic stenosis of the middle cerebral artery.

BACKGROUND: The risk of ischaemic events in asymptomatic intracranial atherosclerosis is unknown. OBJECTIVE: To follow up patients with asymptomatic atherosclerotic middle cerebral artery stenosis (MCAS) to evaluate the long term stroke risk in its territory. METHODS: Consecutive white patients with asymptomatic atherosclerotic MCAS were enrolled. Patients with MCAS of possible or proven non-atherosclerotic origin were excluded. MCAS was assessed by transcranial colour duplex sonography according to published angiography validated criteria. Medical treatment was given at the discretion of the treating physician. RESULTS: 50 patients were included and followed for (mean (SD)) 815 (351) days; three were lost to follow up. MCAS was < 50% in 38 and > or = 50% in 12. No patient suffered an ischaemic event in the MCAS territory; one had a transient ischaemic attack in the contralateral hemisphere. Three patients died, one from a subdural haematoma in the contralateral hemisphere, and two from non-stroke-related causes. Medical treatment at baseline included antithrombotic drugs in 42 cases (antiplatelet agent, n = 39; warfarin, n = 3), and statins in 22; at the end of follow up 45 of the 47 survivors were on antithrombotic drugs (antiplatelet agent, n = 37; warfarin, n = 8), and 30 were on statins. CONCLUSIONS: Asymptomatic MCAS of atherosclerotic origin appears to have a benign long term prognosis with a low risk of ipsilateral stroke in medically treated white patients.