Ralf Dittrich

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.

Mild mechanical traumas are possible risk factors for cervical artery dissection

Background and Purpose: Cervical artery dissection (CAD) is a common cause of ischemic stroke in younger aged subjects. Retrospective studies suggest cervical manipulative therapy (CMT) and preceding infections as extrinsic risk factors for CAD. In a case-control study, we assessed a questionnaire with 7 mild mechanical traumas as potential trigger factors for CAD, including CMT and recent infections. Patients and Methods: Forty-seven consecutive patients with CAD were compared with 47 consecutive patients of similar age with ischemic stroke due to etiologies other than CAD. Patients underwent a standardized face-to-face interview. We assessed head or neck pain and recent infection <7 days before symptom onset, as well as the following mechanical trigger factors <24 h and <7 days prior to symptom onset: (1) heavy lifting, (2) sexual intercourse, (3) mild direct or (4) indirect neck trauma, (5) jerky head movements, (6) sports activity, and (7) CMT. Results:We found no association between any single one of the above risk factors and CAD. CMT (CAD, n = 10; non-CAD, n = 5) and recent infections (CAD, n = 18; non-CAD, n = 10) were more frequent in the CAD group but failed to reach significance. However, the cumulative analysis of all mechanical trigger factors revealed a significant association of mechanical risk factors as a whole in CAD <24 h prior to symptom onset (p = 0.01). Conclusion: Mild mechanical stress, including CMT, plays a role as possible trigger factor in the pathogenesis of CAD. CMT and recent infections alone failed to reach significance during the present investigation, presumably due to the relatively small sample size of the study cohort.

Optimizing the Technique of Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts

Background and Purpose— A cardiac right-to-left shunt (RLS) can be identified by transesophageal echocardiography and transcranial Doppler ultrasound (TCD) with contrast agents and a Valsalva maneuver (VM) as a provocation procedure. This article applies the modalities of these tests detailed in previous studies to a large patient cohort and compares 2 contrast agents (saline and Echovist-300). Methods— Eighty-one patients were investigated by both transesophageal echocardiography and bilateral TCD of the middle cerebral arteries. The following protocol with injections of 10 mL agitated saline was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, and (3) repetition of the test with VM if the first test with VM was negative. The VM was performed for 5 seconds starting exactly 5 seconds after the beginning of saline injection. Thereafter, the same protocol was repeated with 10 mL Echovist-300 instead of saline. Results— Thirty-one patients had a cardiac RLS. The Echovist-300 investigation disclosed all these 31 shunts, but saline disclosed only 29 of them. Twenty-two had an RLS only in at least 1 of the above TCD tests, some of them even with a considerable shunt volume. Conclusions— Contrast TCD performed with Echovist-300 but not with saline yields a 100% sensitivity to identify transesophageal echocardiography-proven cardiac RLSs. The TCD test should be repeated if negative the first time. This article gives detailed information for the optimization of the contrast TCD technique. Extracardiac shunts detected only during contrast TCD can have a considerable shunt volume and may allow for paradoxical embolism.

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.

Prevalence and prognostic impact of microembolic signals in arterial sources of embolism. A systematic review of the literature.

ObjectiveTo compile available studies using microembolic signal (MES) detection by transcranial Doppler sonography in varying sources of arterial brain embolism. We investigated prevalences of MES and whether MES detection is of proven use for risk stratification.MethodStudies reporting prevalences of MES and the risk of cerebral ischemic events were pooled for patients with symptomatic or asymptomatic carotid stenosis, intracranial artery stenosis, cervical artery dissection, and aortic embolism.ResultsMES were reported in 43% of 586 patients with symptomatic and in 10% of 1066 patients with asymptomatic carotid stenosis. Presence of one MES indicated an increased risk of future events [odds ratio (OR): 7.5, 95% confidence interval (CI): 3.6–15.4, p < 0.0001 for symptomatic, and OR: 13.4, 95% CI: 6.5–27.4, p < 0.0001 for asymptomatic disease). MES were reported in 25% of 220 patients with symptomatic vs. 0% of 86 patients with asymptomatic intracranial stenosis (p < 0.0001), Of 82 patients with cervical artery dissection presenting with TIA or stroke, 50% had MES compared with 13% of 16 patients with local symptoms (p = 0.006), In patients with aortic embolism, patients with plaques ≥ 4mm more frequently had MES compared with patients with smaller plaques (p = 0.04), Data were insufficient to reliably predict future events in patients with intracranial stenosis, cervical artery dissection, and aortic embolism.ConclusionMES are a frequent finding in varying sources of arterial brain embolism, MES detection is useful for risk stratification in patients with carotid stenosis.

Prevalence and frequency of microembolic signals in 105 patients with extracranial carotid artery occlusive disease

Besides the established factors “presence of symptoms” and “degree of stenosis”, plaque echolucency is considered to be associated with increased risk of stroke in patients with carotid artery disease. An evaluation was carried out as to whether the prevalence and number of microembolic signals (MES) detected by transcranial Doppler ultrasound were higher in patients with echolucent carotid plaques.  One hundred and five patients with carotid artery stenosis from 20%-99% or occlusion underwent clinical investigations, duplex ultrasound of the carotid arteries, and a 1 hour recording from the middle cerebral artery downstream to the carotid artery pathology using the four gate technique. The presence of MES was more frequent and the number greater in symptomatic patients (21 out of 64 patients (33%); mean number of MES in all 64 patients 3.1) than in asymptomatic patients (four out of 41 patients (10%); mean number of MES in all 41 patients 0.3) (p=0.007, and p=0.006, respectively). Echogenicity of the lesions did not affect either number or presence of MES. Positivity for MES and the number of MES increased with increasing degree of stenosis (both p=0.002). Four out of 12 patients with carotid artery occlusion showed MES. No MES could be detected in carotid artery stenosis below 80%. There was a decline in positivity of MES and of the number of MES with the time after the ischaemic event. After 80 days or more after the index event, only one patient showed MES.  In conclusion, increasing degree of stenosis and presence of symptoms similarly affect macroembolic and microembolic risk. Thus MES may be a surrogate parameter for risk of stroke. The presence of MES in a few asymptomatic patients suggests that clinically silent circulating microemboli may give additional information on the pending embolic potential of carotid artery stenoses. Echolucency of the plaque was not related to an increased number of MES.

Low rate of contrast-induced Nephropathy after CT perfusion and CT angiography in acute stroke patients

BackgroundThe aim of the study was to assess (i) the rate of contrast-induced nephropathy (CIN), (ii) the amount and time course of renal dysfunction, (iii) the identification of risk factors and calculation of a risk score for CIN in acute stroke patients after CT perfusion (CTP) and CT angiography (CTA).Methods162 patients were investigated,who had received 140 ml of non-ionic low osmolar contrast agent (300 mg iodine per ml, Ultravist 300®, Schering AG) for CTA and CTP. We assessed electrolytes, creatinine, and creatinine clearance before and up to 7 days after administration of contrast agent. In addition, the risk factors for CIN were recorded and a previously validated risk score for CIN was calculated.We also assessed the amount of crystalloid fluid substitution and newly prescribed drugs. CIN was defined as an increase of the serum creatinine-level of > 0.5 mg/dl or > 25% above baseline within 48 hours after contrast agent administration.Results154 patients (94 %) received crystalloid fluid substitution (mean 6.1 l) within 48 h after contrast agent administration. During follow-up the creatinine values and the creatinine clearance remained stable while sodium and potassium increased significantly (p < 0.0001) after contrast agent administration. In patients with a pathological creatinine value on admission (n = 40), the creatinine clearance did not decrease significantly (p = 0.18). The risk score for developing a CIN was low in the majority of stroke patients. A manifest CIN occurred in 3 patients (2 %). No patient had to be hemodialysed.ConclusionCIN is a rare complication in acute stroke patients examined by multimodal contrast-based CT due to the low prevalence of risk factors associated with CIN. In conjunction with appropriate fluid substitution, low osmolar nonionic contrast agents seem to be safe in clinical routine.

Intravenous lacosamide—An effective add-on treatment of refractory status epilepticus

Status epilepticus (SE) is a frequent neurological emergency requiring immediate treatment. Therapy usually requires intravenous anticonvulsive medication. Lacosamide is a novel anticonvulsant drug that is available as infusion solution. We describe seven patients with focal SE who were treated with intravenous Lacosamide. All patients in our case series were unsuccessfully treated with other antiepileptic drugs before Lacosamide i.v. was added. In all cases, SE was terminated within 24 h after Lacosamide. There were no serious side effects or adverse events attributable to Lacosamide i.v. Our data suggest that Lacosamide might be an effective add-on treatment, if standard drugs fail or are unsuitable.

High-resolution Magnetic Resonance Imaging (mri) at 3.0 Tesla in the Short-term Follow-up of Patients With Proven Cervical Artery Dissection

Purpose:For the imaging evaluation of patients with suspected cervical artery dissection (CAD) in the last decade, magnetic resonance imaging (MRI) has become the first line imaging modality. However, CAD is a highly dynamic process with rapid changes over time. Aim of this study was to assess the short-term morphologic changes in patients with proven CAD by MRI within 2 weeks after the initial diagnosis using a multicontrast high-resolution noninvasive vessel wall imaging approach at 3.0 T. Materials and Methods:Eighty-two patients with clinically suspected CAD were examined using a 3.0 T system (Gyroscan Intera, Philips). Imaging protocol consisted of 3-dimensional inflow MRA (repetition time [TR]/echo time [TE]/flip angle [FA] = 25 milliseconds/3.1 milliseconds/16 degrees, reconstructed voxel size 0.3 × 0.3 × 0.8 mm), black blood T1w 3-dimensional spoiled gradient echo (TR/TE/FA = 31 milliseconds/7.7 milliseconds/15 degrees, 0.3 × 0.3 × 1.0 mm), and fat suppressed T2w turbo spin echo (TSE) (TR/TE/echo train length = 3 heart beats/44 milliseconds/7, 0.3 × 0.3 × 2 mm). Three observers in consensus performed image analysis. Images were assessed with regard to presence and size of intramural hematoma, degree of stenosis, presence of intraluminal thrombus, development of pseudoaneurysm, and incidence of additional dissections. In 29 patients (35%) a dissection had initially been proven by direct visualization of an intramural hematoma. Twenty-one patients (72%; 7 male, 14 female; mean age 41.5 years) were available for follow-up studies leading to a total of 24 diseased cervical arteries being reevaluated 2 weeks later for prospective follow-up. Results:Mean interval between initial study and follow-up was 14.2 days (range 7-30 days). Eighteen patients had presented with an acute CAD in 1 artery, 3 patients with an acute CAD in 2 arteries. At follow-up, degree of stenosis had increased in 2 arteries, remained unchanged in 13, and decreased in 5 arteries. Four initially occluded arteries were recanalized at follow-up. In 3 arteries a pseudoaneurysm had been visible in the initial study and remained unchanged at follow-up; in 1 artery a new pseudoaneurysm was observed. In 3 arteries, new dissections were identified during follow-up. Conclusion:High-resolution MRI of acute CAD at 3.0 T permits a refined cross-sectional and longitudinal analysis of the morphologic features of CAD. The increased signal-to-noise ratio at 3.0 T allows for a high spatial resolution permitting detailed analysis of the diseased vessel segment. An unequivocal distinction between intramural hematoma and thrombus was possible. Information could be gained with regard to recanalization, degree of stenosis, formation of pseudoaneurysm, and appearance of new dissections making short-term follow-up in pts with acute CAD recommendable. Further studies are needed to assess the relationship between short-term results and definite outcome.

Spontaneous acute dissection of the internal carotid artery: high-resolution magnetic resonance imaging at 3.0 tesla with a dedicated surface coil.

Purpose:Magnetic Resonance Imaging (MRI) has become the method of choice in the evaluation of patients with suspected cervical artery dissection (CAD). However, reliable identification of acute CAD might be impaired by the limited spatial resolution of standard 1.5 T MRI. In this preliminary study, we implemented a multicontrast high-resolution noninvasive vessel wall imaging approach at 3.0 T in patients with spontaneous CAD. Methods and Materials:Ten patients with CAD of the internal carotid artery (ICA) were included in the study. 3.0 T MRI (Gyroscan Intera, Philips) was acquired using a dedicated phased-array coil. MRI-protocol consisted of: (1) bright blood 3D inflow MRA (TR/TE/FA = 25 milliseconds/3.1 millisecond/16°, 120 slices, reconstructed voxel size 0.3 × 0.3 × 0.8 mm); (2) black blood cardiac-gated water-selective T1w 3D spoiled GE (TR/TE/FA = 31 milliseconds/7.7 milliseconds/15°, 36 slices, 0.3 × 0.3 × 1.0 mm); and (3) black blood cardiac triggered fat suppressed T2w TSE (TR/TE/ETL = 3 heart beats/44 milliseconds/7, 18 slices, 0.3 × 0.3 × 2 mm). Three observers in consensus performed image analysis. Special attention was paid to the integrity of the luminal and adventitial vessel boundary and the presence of a communicating intimal tear or flap. Results:3.0 T MRI provided excellent delineation of vessel lumen and vessel wall as a result of the nearly complete suppression of arterial blood signal. An intramural hematoma could be identified in all patients, confined between the luminal and adventitial vessel boundary. In no patient a communicating intimal tear could be identified. Clear distinction between intramural hematoma and thrombus was possible. Conclusion:High-resolution vessel wall imaging in patients with acute CAD is feasible. The increased signal-to-noise ratio at 3.0 T can be invested to obtain a higher spatial resolution, permitting depiction of intimal and adventitial vessel wall boundary and the intramural hematoma in the diseased vessel segment. The morphologic information that is gained is helpful in the understanding of the underlying pathomechanismen of CAD.