Tobias Brandt

Thrombolytic Therapy of Acute Basilar Artery Occlusion: Variables Affecting Recanalization and Outcome

BACKGROUND AND PURPOSE Thrombolysis may reduce mortality after acute basilar artery (BA) occlusion. We intended to find variables affecting recanalization and clinical outcome in patients with BA occlusion undergoing thrombolytic therapy. METHODS We analyzed in retrospect the clinical and angiographic data of a consecutive series of 51 patients treated with intra-arterial urokinase (n = 44; 0.3 to 1.5 mIU) or intravenous or intra-arterial recombinant tissue plasminogen activator (n = 7; 22 to 100 mg). We identified effective variables by multiple logistic regression analyses and univariate tests. RESULTS Sites of occlusion were the caudal (n = 23), middle (n = 18), and distal (n = 10) segments of the BA. The pathogenesis was embolism in 35 and local atherothrombosis in 16 patients. Collateral circulation was good in 32 patients and poor or absent in 19 patients. Recanalization was achieved in 26 of 51 (51%) patients and was associated with occlusions of embolic etiology (P = .0025). Mortality was 46% (12/26) in the recanalization group and 92% (23/25) in the nonrecanalization group (P = .0004). Other independent variables affecting mortality were length of BA obstruction (P = .0011), age (P = .0008), and collateral state (P = .0454). After follow-up (median, 32 months), 10 of the 16 survivors were only minimally impaired, with a Barthel Index score of 95 or greater; 5 patients were moderately and 1 severely disabled. CONCLUSIONS Recanalization of acute BA occlusion reduces mortality significantly. Length of BA obstruction and state of the collaterals are additional independent variables affecting survival. Young patients with monosegmental embolic occlusion of the BA seem to have the best chance to considerably profit from thrombolysis.

Pathogenesis of cervical artery dissections Association with connective tissue abnormalities

Background: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been postulated. Objective: To further assess the association of CAD with ultrastructural abnormalities of the dermal connective tissue. Methods: In a multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron microscopy. Results: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65 patients (55%), consisting of the regular occurrence of composite fibrils within collagen bundles that in some cases resembled the aberrations found in Ehlers–Danlos syndrome type II or III and elastic fiber abnormalities with minicalcifications and fragmentation. A grading scale according to the severity of the findings is introduced. Intraindividual variability over time was excluded by a second biopsy of the skin in eight patients with pronounced aberrations. Recurrent CAD correlated with connective tissue aberrations. In addition, similar connective tissue abnormalities were detected in four first-degree relatives with familial CAD. Conclusion: CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

Leukocyte Count as an Independent Predictor of Recurrent Ischemic Events

Background and Purpose— Inflammatory markers predict first-time ischemic events. We investigated whether leukocyte and differential counts predict recurrent events and ischemic events in high-risk populations, and whether such events are preceded by acutely exacerbated inflammation. Methods— We studied 18 558 patients with ischemic stroke, myocardial infarction, or peripheral arterial disease who participated in the trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE), a study that compared the occurrence of ischemic stroke, myocardial infarction, or vascular death under randomized treatment with aspirin or clopidogrel. Leukocyte counts were frequently assessed during followup. Results— Compared with the quartile with lowest leukocyte counts at baseline (<5.9× 109/L), patients in the top quartile (>8.2× 109/L) had higher risks for ischemic stroke (relative risk 1.30; P < 0.007), myocardial infarction (relative risk 1.56, P < 0.001), and vascular death (relative risk 1.51; P < 0.001) after adjustment for other risk factors. Neutrophil counts contributed most to increased risk. Assessments of regression dilution effects based on replicate measurements show that these risk associations may underestimate the real associations by 30 to 50%. Treatment with aspirin or clopidogrel did not influence predictive effects by leukocytes. In the week before a recurrent event, but not at earlier time points, the leukocyte count was significantly increased over baseline levels (n= 211; mean difference +0.46×109/L; P = 0.005). Conclusions— Leukocyte counts and mainly neutrophil counts are independently associated with ischemic events in these high-risk populations. An increase of leukocyte counts over baseline levels heralds a period of increased risk lasting about one week.

Role of CT Angiography in Patient Selection for Thrombolytic Therapy in Acute Hemispheric Stroke

BACKGROUND AND PURPOSE It has been shown that thrombolytic therapy can improve clinical outcome in a subgroup of patients with acute cerebral ischemia. This subgroup was characterized by certain clinical and imaging findings (eg, moderate to severe neurological deficit for less than 3 to 6 hours, occlusion of the middle cerebral artery, lack of extended infarct signs on CT, and efficient leptomeningeal collaterals). Although not part of published prospective randomized rtPA trials, information about the status of the brain vessels would be helpful in the selection of patients who may benefit the most. Our purpose was to determine the feasibility of CT angiography (CTA) in patients with acute hemispheric ischemia and to evaluate its relevance for thrombolytic therapy. METHODS CTA was performed in 40 consecutive patients (11 women and 29 men; age range, 19 to 80 years) with moderate or severe symptoms (National Institutes of Health Stroke Scale score of > or =8) of acute hemispheric ischemia. CTA findings were compared with Doppler ultrasonography (US; n=22) and intra-arterial digital subtraction angiography (DSA; n=7). Twenty patients received thrombolytic therapy, the remaining patients received intravenous heparin. RESULTS Images and 3-dimensional reconstructions of diagnostic quality could be obtained in all patients. Thirty-four patients had a vessel occlusion. The extent of leptomeningeal collaterals correlated significantly with the outcome after thrombolytic therapy (rs=0.46, P<0.05). The evaluation of diagnostic accuracy showed a high agreement with US (22 of 22) and DSA (6 of 7). CONCLUSIONS CTA can provide important information for the initiation of therapy in patients with acute hemispheric ischemia. Identification of patients with autolyzed thrombi, occlusion of the internal carotid artery bifurcation, and poor leptomeningeal collaterals is feasible with the use of CTA. These patients may have little potential for benefit from thrombolytic therapy.

Antiplatelets Versus Anticoagulation in Cervical Artery Dissection

Background and Purpose— The widespread preference of anticoagulants over antiplatelets in patients with cervical artery dissection (CAD) is empirical rather than evidence-based. Summary of Review— This article summarizes pathophysiological considerations, clinical experiences, and the findings of a systematic metaanalysis about antithrombotic agents in CAD patients. As a result, there are several putative arguments in favor as well as against immediate anticoagulation in CAD patients. Conclusions— A randomized controlled trial comparing antiplatelets with anticoagulation is needed and ethically justified. However, attributable to the large sample size which is required to gather meaningful results, such a trial represents a huge venture. This comprehensive overview may be helpful for the design and the promotion of such a trial. In addition, it could be used to encourage both participation of centers and randomization of CAD patients. Alternatively, antithrombotic treatment decisions can be customized based on clinical and paraclinical characteristics of individual CAD patients. Stroke severity with National Institutes of Health Stroke Scale score ≥15, accompanying intracranial dissection, local compression syndromes without ischemic events, or concomitant diseases with increased bleeding risk are features in which antiplatelets seem preferable. In turn, in CAD patients with (pseudo)occlusion of the dissected artery, high intensity transient signals in transcranial ultrasound studies despite (dual) antiplatelets, multiple ischemic events in the same circulation, or with free-floating thrombus immediate anticoagulation is favored.

Posterior Cerebral Artery Territory Infarcts: Clinical Features, Infarct Topography, Causes and Outcome1

Only a few large series of posterior cerebral artery (PCA) stroke exist, and clinical features and causes have not been studied as extensively as in other vascular territories. The PCA syndrome includes more clinical signs than the well-known visual field deficits. Concomitant findings are frequently sensory, slight motor and neuropsychological deficits. Unilateral headaches are the common presenting symptom making complicated migraine an important differential diagnosis. Combined deep and superficial PCA territory infarcts involving the lateral thalamus are more frequent than commonly assumed and are mostly associated with sensory and reversible slight motor deficits. Occlusion of the precommunal PCA segment with associated paramedian midbrain infarction causes severe motor deficits, oculomotor signs, and decreased consciousness and has a poorer outcome than other PCA territory infarcts. Embolism from a cardiac or undetermined source is the leading mechanism accounting for up to half of the cases, whereas arterial embolism from significant proximal vertebrobasilar disease is less frequent. Local atherothrombotic stenosis or occlusion of the PCA is uncommon. In spite of thorough diagnostic evaluation, the etiology of PCA territory infarction cannot be determined in at least one quarter of patients. Among the rare causes of PCA territory infarction carotid artery disease is important while the significance of migraine remains controversial.Only a few large series of posterior cerebral artery (PCA) stroke exist, and clinical features and causes have not been studied as extensively as in other vascular territories. The PCA syndrome includes more clinical signs than the well-known visual field deficits. Concomitant findings are frequently sensory, slight motor and neuropsychological deficits. Unilateral headaches are the common presenting symptom making complicated migraine an important differential diagnosis. Combined deep and superficial PCA territory infarcts involving the lateral thalamus are more frequent than commonly assumed and are mostly associated with sensory and reversible slight motor deficits. Occlusion of the precommunal PCA segment with associated paramedian midbrain infarction causes severe motor deficits, oculomotor signs, and decreased consciousness and has a poorer outcome than other PCA territory infarcts. Embolism from a cardiac or undetermined source is the leading mechanism accounting for up to half of the cases, whereas arterial embolism from significant proximal vertebrobasilar disease is less frequent. Local atherothrombotic stenosis or occlusion of the PCA is uncommon. In spite of thorough diagnostic evaluation, the etiology of PCA territory infarction cannot be determined in at least one quarter of patients. Among the rare causes of PCA territory infarction carotid artery disease is important while the significance of migraine remains controversial.

Differential features of carotid and vertebral artery dissections The CADISP Study

Objective: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. Methods: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). Results: Patients with ICAD were older (p < 0.0001), more often men (p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09–2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56–1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01–1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27–0.48]) or had cerebral ischemia (OR = 0.32 [0.21–0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12–1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13–2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42–0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32–6.88]), but this was no longer significant after adjusting for baseline NIHSS score. Conclusion: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.

Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection

Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defined by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass effect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be difficult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confirm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

Infection-Associated Cervical Artery Dissection Three Cases

BACKGROUND The pathogenesis of cervical artery dissection remains unknown. Infection-mediated damage of the arterial wall may be one contributing mechanism. We present three male patients with respiratory infection prior to cervical artery dissection. CASE DESCRIPTIONS Case 1: During an upper respiratory tract infection, a 49-year-old patient developed bilateral carotid and vertebral artery dissection with complete vessel restitution. Case 2: Within 3 years, a 40-year-old patient experienced two episodes of bilateral internal carotid artery dissection, both preceded by febrile upper respiratory tract infection. Case 3: A 52-year-old patient developed right-sided and, 2 years later, left-sided internal carotid artery dissection, each following upper respiratory tract infection. CONCLUSIONS Infection may be a trigger factor in the pathogenesis of cervical artery dissection.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10−3; combined P = 1.00 × 10−11). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.