Michael Rosenkranz

Negative fluid-attenuated inversion recovery imaging identifies acute ischemic stroke at 3 hours or less†

o evaluate the use of fluid‐attenuated inversion recovery (FLAIR) imaging as surrogate marker of lesion age within the first 6 hours of ischemic stroke.

Two Tales: Hemorrhagic Transformation but Not Parenchymal Hemorrhage After Thrombolysis Is Related to Severity and Duration of Ischemia: MRI Study of Acute Stroke Patients Treated With Intravenous Tissue Plasminogen Activator Within 6 Hours

Background and Purpose— Intracerebral hemorrhage represents the most feared complication of treatment with intravenous tissue plasminogen activator. We studied whether perfusion-weighted imaging and diffusion-weighted imaging has the potential to identify patients at risk of severe intracerebral hemorrhage after treatment with intravenous tissue plasminogen activator. Methods— We analyzed data of prospectively studied MRI selected acute ischemic stroke patients treated with intravenous tissue plasminogen activator within 6 hours. All patients were examined by perfusion- and diffusion-weighted imaging ≤6 hours. Perfusion- and diffusion-weighted imaging lesion volumes were calculated. Hemorrhagic transformation was assessed on follow-up CT or MRI and diagnosed as hemorrhagic transformation, parenchymal hemorrhage, or symptomatic intracerebral hemorrhage according to ECASS II criteria. Results— Of 152 patients, hemorrhagic transformation was seen in 60 (39.5%), parenchymal hemorrhage in 15 (9.9%), and symptomatic intracerebral hemorrhage in 4 (2.6%). Multiple logistic regression analysis identified onset to treatment time after 3 to 6 hours (P<0.001), a larger perfusion-weighted imaging lesion volume (P=0.002), and, as a tendency, a higher score on the National Institutes of Health Stroke Scale on admission (P=0.068) as independent predictors of hemorrhagic transformation. Neither MRI lesion volumes nor severity of symptoms, but rather only an older age tended to be associated with parenchymal hemorrhage (P=0.087). Conclusion— Our results further support the concept of a different pathogenesis for hemorrhagic transformation and parenchymal hemorrhage. Whereas hemorrhagic transformation should be regarded as a clinically irrelevant epiphenomenon of ischemic damage and reperfusion, parenchymal hemorrhage appears to be related to biologic effects of tissue plasminogen activator and other pre-existing pathologic conditions, which deserve further investigation.

AXIS A Trial of Intravenous Granulocyte Colony-Stimulating Factor in Acute Ischemic Stroke

Background and Purpose— Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data. Methods— Four intravenous dose regimens (total cumulative doses of 30–180 &mgr;g/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch. Results— Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions >14–17 cm3. Conclusions— We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.

Reperfusion after Severe Local Perfusion Deficit Precedes Hemorrhagic Transformation: An MRI Study in Acute Stroke Patients

Background: We applied magnetic resonance imaging to analyze the degree of local diffusion and perfusion abnormalities and the status of reperfusion in regions with subsequent hemorrhagic transformation (HT). Methods: 51 patients with acute ischemic stroke were studied by diffusion- and perfusion-weighted imaging within 3.0 ± 0.8 h, on day 1 and days 5–8. After realignment of the image data sets, the parameter maps of the apparent diffusion coefficient (ADC), cerebral blood flow (CBF) and cerebral blood volume (CBV), and mean transit time were analyzed in the area of subsequent HT. The degree of local diffusion and perfusion impairment in the HT area was compared with the entire diffusion and perfusion abnormality. Reperfusion status was separately assessed for the entire perfusion abnormality and the HT area. Results: HT was observed in 19/51 patients (37.2%) within 8 days after symptom onset. Areas destined for HT revealed a more severe decrease in ADC (to 70 ± 13%; p < 0.01), CBV (to 31 ± 26%; p < 0.001) and CBF (to 28 ± 19%; p < 0.001) compared to the entire perfusion abnormality. Local reperfusion in the HT area was seen in 18/19 patients. The presence of HT did not coincide with a worse clinical outcome. Discussion: HT is the result of reperfusion in the region with the most severe local perfusion impairment and does not influence the neurological outcome.

Anterior spinal artery syndrome following periradicular cervical nerve root therapy

Sirs: A 44-year-old man suffered from intractable neck pain with irradiation into his left arm due to discogenic compression of the left C7-nerve root. It was decided to treat the patient with CT-controlled periradicular therapy (PRT). The tip of a 22-gauge needle was positioned in the posteriorcaudal corner of the left C6/C7foramen. After adequate position of the needle had been confirmed by injection of 0.2 ml iotrolan (Isovist 300, Schering, Germany), a mixture of 1 ml mepivacaine 1 % and 0.5 ml triamcinolone acetonide (20 mg) crystal suspension was injected without adrenaline admixture. Within 3 minutes the patient developed an anterior spinal artery syndrome with complete flaccid quadriplegia including respiratory muscles, paralysis of sphincteric function, and dissociated sensory loss below the level of C4. Colorcoded duplex sonography of the vertebral arteries was normal. T2weighted MRI of the spine performed 6 hours after the onset of symptoms showed longitudinal central signal enhancement of the cervical spinal cord (Fig. 1A). MRI performed 6 days after the incident LETTER TO THE EDITORS

Pretreatment Diffusion-Weighted Imaging Lesion Volume Predicts Favorable Outcome After Intravenous Thrombolysis With Tissue-Type Plasminogen Activator in Acute Ischemic Stroke

Background and Purpose— Stroke magnetic resonance imaging with perfusion and diffusion weighting has shown its potential to select patients likely to benefit from intravenous thrombolysis with tissue-type plasminogen activator (IV-tPA). We aimed to determine the predictors of favorable outcome in magnetic resonance imaging–selected, acute stroke patients treated with IV-tPA. Methods— We analyzed the data of acute ischemic stroke patients from a prospective, multicenter, observational study of magnetic resonance imaging–based IV-tPA treatment initiated ⩽6 hours from symptom onset. Neurologic deficit on admission was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90 days according to the modified Rankin Scale. Favorable outcome was defined as a modified Rankin Scale score of 0 to 1. Patients were compared regarding baseline parameters. Multivariate regression analysis was used to identify predictors of favorable outcome. Results— Of 174 patients, 83 (48%) reached a favorable outcome. They were younger (median age, 62 versus 67 years; P=0.001), had a lower National Institutes of Health Stroke Scale score on admission (median, 11 versus 15; P<0.001), and had smaller diffusion-weighted imaging lesions (median, 12.9 versus 20 mL; P=0.001). Perfusion-weighted imaging lesion volumes and onset-to-treatment time were comparable between the groups. Age (P=0.017), National Institutes of Health Stroke Scale score on admission (P<0.001), and diffusion-weighted imaging lesion volume (P=0.047) were identified as independent predictors of favorable outcome. Conclusions— A lower age, lower National Institutes of Health Stroke Scale score on admission, and smaller pretreatment diffusion-weighted imaging lesion volume were found to be associated with a favorable outcome after treatment with IV-tPA. Pretreatment perfusion lesion volume and onset-to-treatment time were not associated with outcome when patients were selected for IV-tPA by magnetic resonance imaging within 6 hours of symptom onset.

Reduced Perception of Dyspnea and Pain after Right Insular Cortex Lesions

RATIONALE The perception of dyspnea and pain show many similarities. Initial imaging studies suggested an important role of the insular cortex for the perception of both sensations. However, little is known about the cortical processing of dyspnea. OBJECTIVES This study investigated the influence of lesions of the insular cortex on the perception of dyspnea and pain. METHODS Dyspnea was induced by resistive loaded breathing in four patients with right-hemispheric insular cortex lesions, as assessed with computer tomography or magnetic resonance imaging, and four matched healthy control subjects. Pain was induced by a cold-pressor test. Perceived intensity and unpleasantness of both sensations were rated on visual analog scales. MEASUREMENTS AND MAIN RESULTS In contrast to healthy control subjects, patients with lesions demonstrated reduced perceptual sensitivity for dyspnea, in particular for the unpleasantness of dyspnea (P < 0.05). This was paralleled by reduced sensitivity for pain in patients with lesions, as reflected by smaller ratings of intensity and unpleasantness, higher sensory pain-thresholds, and, in particular, higher affect-related pain tolerance times (P < 0.05). CONCLUSIONS The results suggest that lesions of the right insular cortex are associated with reduced sensitivity for the perception of dyspnea and pain, in particular for their perceived unpleasantness. This underlines the importance of the insular cortex for the perception of both sensations.

Are There Time-Dependent Differences in Diffusion and Perfusion Within the First 6 Hours After Stroke Onset?

Background and Purpose— Stroke heterogeneity in computed tomography-based studies has been attributed as main cause for missing efficacy of intravenous tissue plasminogen activator (tPA) therapy within 3 to 6 hours. We investigated early time-dependent differences in acute stroke pathophysiology by multiparametric magnetic resonance imaging (MRI). Methods— Stroke MRI of 112 acute ischemic stroke patients within <6 hours were dichotomized into a <3-hour group (n=52) and a 3- to 6-hour group (n=60). Infarct volume was determined on days 5 to 8. Lesion volumes were determined for apparent diffusion coefficient (ADC_man) and the subregion with ADC values <550×10−9 mm/s 2 (ADC <550), and for the time-to-peak (TTP) delay of 2 to 4 seconds, 4 to 6 seconds, 6 to 8 seconds, and >8 seconds. A subsample analysis was performed for occlusions of the middle carotid artery (MCA) trunk (n=36) and MCA branches (n=30), and for all patients treated by intravenous tPA (n=70). Results— ADC and TTP lesion volumes were not different within <3 hours compared with volumes at 3 to 6 hours. In patients receiving intravenous tPA (n=70), there were no significant differences in ADC_man, TTP >2 seconds, and infarct volume (days 5 to 8) between the 2 groups. There was a greater proportion of ADC <550/ADC_man, which was most pronounced in patients with MCA trunk occlusions after 3 to 6 hours and a larger mismatch in the <3-hour group compared with that of the 3- to 6-hour group. In MCA branch occlusions, there was a less severe TTP delay after 3 to 6 hours. However, all differences missed the significance level (P =0.05) after correction for multiple testing. Conclusions— We observed no significant time-dependent differences within 6 hours after stroke onset in degree and volume of diffusion and perfusion impairment. An exclusion from intravenous tPA solely based on a rigid 3-hour time window seems unjustified in MRI-confirmed ischemic stroke.

Streptococcus suis meningitis and septicemia contracted from a wild boar in Germany.

Sirs: A 51-year-old man was admitted to the hospital with dizziness, headache, neck rigidity, nausea, and progressive loss of consciousness. The body temperature was 39.0 °C, white cell count was 20.0x10E9/l (95 % neutrophils), and C-reactive protein was 236 mg/l. Computed tomography (CT) showed brain edema with basal swelling, meningeal contrast enhancement, and dilated ventricles that had to be drained for 10 days. Cerebrospinal fluid (CSF) was turbid with a polymorphonuclear pleocytosis (1,251 cells/μl), protein of 1,924 mg/l, and lactate of 7.2 mmol/l. Gram stain showed pairs and short chains of Grampositive coccoid rods (Fig. 1). Streptococcus pneumoniae meningitis or Listeria meningitis was suspected. Antibiotic treatment consisted of 2 g ceftriaxone, 6 g ampicillin, and 240 mg gentamicin for 14 days. Both blood and CSF cultures (Mueller-Hinton agar, 5 % sheep blood) grew beta-hemolytic streptococci that were identified as Streptococcus suis using ID 32 Strep (bioMérieux, France) (Fig. 2). Serological evaluation by the German national reference laboratory for streptococci (Department of Microbiology, University of Aachen, Germany) identified the isolate as Streptococcus suis type 2, Lancefield group R. There was no evidence of a source of infection such as endocarditis or ear infection, but dental examination revealed a carious molar with a purulent chronic gingival inflammation. During the following days the patient developed septicemia and multiple CT-proven septic-embolic infarctions of the left kidney. After regaining consciousness the patient was found to have bilateral perceptive deafness, and extensive bilateral visual field deficits. As fundoscopy was normal, and CT and magnetic resonance imaging of the brain did not show cerebral lesions that may have been responsible for visual field deficits, septic-embolic infarctions of the optic nerves were suspected. Three months later the patient still suffered from perceptive deafness despite external hearing devices. The binocular visual field deficits had slightly improved. The history of the patient’s lifestyle and habits regarding porcine exposure revealed that he never had contact to domestic pigs. However, the patient was a recreational hunter and had shot and butchered a wild sow two days preceding the onset of clinical symptoms. While butchering the dead wild sow, he accidentally dropped a stick of wood out of his mouth on which he habitually chewed while hunting, intuitively picked it back up, and continued chewing on it. Hence the purulent gingivitis mentioned is the most likely port of entry. Streptococcus suis infection is a porcine zoonosis that may cause meningitis in man [2]. The causative agent is Streptococcus suis type 2, which may be isolated from palatine tonsils of its natural host, the domestic pig [1, 4]. The incidence of Streptococcus suis meningitis in subjects occupationally exposed to domestic pigs has been reported to be 3/100,000, almost 1,500-times higher than among persons not working in the pigrearing industry [2]. However, to our knowledge, only three cases of human infection have been traced to wild boars [3, 5, 6]. Perceptive deafness may be found in up to 67 % of patients with Streptococcus suis meningitis [2, 8, 9] and is suggested to result from cochlear sepsis rather than eighth cranial nerve involvement [7]. Septicemia is a major complication of Streptococcus suis infection [2], but septicembolic infarctions of the kidney and of the optic nerves have not previously been reported. The present report emphasizes LETTER TO THE EDITORS

Cerebral Embolism during Carotid Artery Stenting: Role of Carotid Plaque Echolucency

Background: Carotid artery stenting (CAS) is associated with the risk of intraprocedural stroke. A better understanding of specific risk factors could help to improve the procedure and to reduce the overall risk of CAS. We addressed the role of carotid plaque echolucency as potential risk factor for cerebral embolism during CAS. Methods: We prospectively evaluated carotid plaque echolucency by use of a computer-assisted measure of echogenicity, the gray scale median (GSM), in 31 consecutive patients with symptomatic high-grade carotid stenosis that were scheduled to undergo CAS. Dual-frequency transcranial Doppler ultrasound was used to detect solid cerebral microemboli during CAS. Results: 27 of the 31 patients met all inclusion/exclusion criteria.Solid cerebral microemboli were detected during 17 of 27 CAS procedures. The GSM of the target plaques was lower in subjects with intraprocedural embolism (37.9 ± 20.8) than in those without (58.2 ± 25.7) (p = 0.040). A receiver-operating characteristic analysis showed that the GSM that gave the greatest separation between plaques with a higher and a lower probability of intraprocedural embolism was 50: the proportion of subjects with intraprocedural embolism was 85% in CAS of echolucent plaques (GSM <50) and 42% in CAS of echogenic plaques (GSM ≥50) (p = 0.031). Conclusions: CAS of both echolucent and echogenic carotid plaques may be associated with cerebral embolism, particularly CAS of echolucent plaques. Plaque echolucency alone does not reliably identify patients at particularly high risk of intraprocedural embolism, but should be considered as one of a broad panel of risk factors of CAS.