E. B. Ringelstein

Noninvasive Determination of Language Lateralization by Functional Transcranial Doppler Sonography A Comparison With the Wada Test

BACKGROUND AND PURPOSE Functional transcranial Doppler ultrasonography (fTCD) can assess event-related changes in cerebral blood flow velocities and, by comparison between sides, can provide a measure of hemispheric perfusional lateralization. It is easily applicable, insensitive to movement artifacts, and can be used in patients with less than perfect cooperation. In the present study we investigated the validity of fTCD in determining the hemispheric dominance for language by direct comparison of fTCD with intracarotid amobarbital anesthesia (Wada test). METHODS fTCD and the Wada test were performed in 19 patients evaluated for epilepsy surgery. By the Wada test, 13 patients were classified as left-hemisphere dominant and 6 as right-hemisphere dominant for language. fTCD was based on the continuous bilateral measurements of blood flow velocities in the middle cerebral arteries and event-related averaging during a cued word generation task previously shown to activate lateralized language areas in normal adults. RESULTS In 4 patients fTCD assessment was not possible because of lack of an acoustic temporal bone window. In the remaining 15 candidates, determination of language dominance was concordant with the Wada test in every case. Moreover, the correlation of the lateralization measures from both procedures was highly significant (r=.92, P<.0001). CONCLUSIONS This strong correlation validates fTCD as a noninvasive and practical tool for the determination of language lateralization that can be applied for clinical and investigative purposes.

Degree of language lateralization determines susceptibility to unilateral brain lesions

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

Pneumonia in acute stroke patients fed by nasogastric tube

Background: Aspiration pneumonia is the most important acute complication of stroke related dysphagia. Tube feeding is usually recommended as an effective and safe way to supply nutrition in dysphagic stroke patients. Objective: To estimate the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to determine risk factors for this complication, and to examine whether the occurrence of pneumonia is related to outcome. Methods: Over an 18 month period a prospective study was done on 100 consecutive patients with acute stroke who were given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and artificial ventilation. Functional outcome was assessed at three months. Logistic regression and multivariate regression analyses were used, respectvely, to identify variables significantly associated with the occurrence of pneumonia and those related to a poor outcome. Results: Pneumonia was diagnosed in 44% of the tube fed patients. Most patients acquired pneumonia on the second or third day after stroke onset. Patients with pneumonia more often required endotracheal intubation and mechanical ventilation than those without pneumonia. Independent predictors for the occurrence of pneumonia were a decreased level of consciousness and severe facial palsy. The NIH stroke scale score on admission was the only independent predictor of a poor outcome. Conclusions: Nasogastric tubes offer only limited protection against aspiration pneumonia in patients with dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the illness and patients with decreased consciousness and a severe facial palsy are especially endangered.

Detectability of cerebral hemisphere ischaemic infarcts by CT within 6 h of stroke

To determine how early and how reliably ischaemic brain infarcts can be detected on CT within 6 h of the onset of cerebral hemisphere strokes, 44 such studies were interpreted by an experienced neuroradiologist blinded to clinical signs, but aware that the cohort was a stroke population. He was asked to detect and localise an area of parenchymal low density and/or focal brain swelling. A follow-up study showing the definite infarct served as a reference in each case. In 38 patients areas of slightly low density were seen, and in 36 follow-up CT confirmed infarcts in the locations indicated. In 2 patients the reading was false positive. In 6 patients no low density focus could be detected. In these 8 patients examined by CT within 180 min of the stroke, no low density could be identified, even in retrospect with the knowledge of the findings on follow-up. Thus, 42 readings (95%) were true positive or true negative; 2 were false positive; and none was a false negative. CT within 6 h of the onset of symptoms has a mean sensitivity of 82% (36/44) for ischaemic cerebral hemisphere infarcts. By contrast, its sensitivity to ischaemic parenchymal low density is low during the initial 2 h. The early development of hemispheric infarcts can be detected reliably if the radiologist is familiar with the signs.

Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function

Objective: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). Methods: We cross-sectionally examined 447 community-dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. Results: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (β = −0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (β = −0.237, p < 0.001), as well as regional FA scores of the frontal lobes (β = −0.246, p < 0.001), the corona radiata (β = −0.222, p < 0.001), and the corpus callosum (β = −0.141, p = 0.016), in particular the genu (β = −0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. Conclusion: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.

AVERAGE: A Windows® program for automated analysis of event related cerebral blood flow

Functional transcranial Doppler sonography (fTCD) is used to measure changes in brain perfusion during different states of brain activity by evaluating flow velocities within the major brain arteries. We developed a computer program called AVERAGE which can be used with various TCD devices and allows for subtle quantitative off-line analysis of Doppler flow signals. AVERAGE supports data transformation, heart beat analysis, noise reduction, trigger signal and marker modification, artifact analysis and artifact rejection, as well as data reduction. Perfusion differences and their time course within two different arteries can be analyzed by parametric and non parametric statistical methods. This is important, for instance, in studies on hemispherical dominance during mental task processing. Each data processing step is supported by graphical output. If investigated bilaterally with interhemispheric analysis even minimal activations can reliably be detected and quantified with a sensitivity known from positron emission tomography approaches.

Neuroimaging evidence for cortical involvement in the preparation and in the act of swallowing

This study employed whole head magnetoencephalography and synthetic aperture magnetometry to investigate the cortical topography of the preparation and the execution of volitional and reflexive water swallowing and of a simple tongue movement. Concerning movement execution, activation of the mid-lateral primary sensorimotor cortex was strongly lateralized to the left during volitional water swallowing, less strongly lateralized to the left during reflexive water swallowing, and not lateralized at all during tongue movement. In contrast, the preparation for both volitional water swallowing and tongue movement showed a bilateral activation of the primary sensorimotor cortex. No activation was seen prior to reflexive water swallowing. Activation of the left insula and frontal operculum was observed only during both the preparation and the execution of volitional water swallowing. These new findings suggest a left hemispheric dominance for the cortical control of swallowing in humans.

Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts Comparison of Different Procedures and Different Contrast Agents

BACKGROUND AND PURPOSE Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and different provocation procedures. Currently, data on an appropriate time window for the appearance of contrast bubbles in the TCD recording after the injection of the contrast medium and the comparison of different provocation maneuvers to increase right-to-left shunting are insufficient. METHODS Forty-six patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with 6 injection modes was applied in a randomized way: (1) injection of 10 mL of agitated saline without Valsalva maneuver, (2) injection of 10 mL of agitated saline with Valsalva maneuver, (3) injection of 10 mL of a commercial galactose-based contrast agent (Echovist) without Valsalva maneuver, (4) injection of 10 mL of Echovist with Valsalva maneuver, (5) injection of 10 mL of Echovist with standardized Valsalva maneuver, and (6) injection of 10 mL of Echovist with coughing. RESULTS In 20 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt-positive). Sixteen patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 10 patients were only positive on at least 1 TCD investigation but negative during TEE. The amount of microbubbles detected in the various tests decreased in the following order: Echovist and Valsalva maneuver, Echovist with coughing, Echovist and standardized Valsalva maneuver, saline with Valsalva maneuver, Echovist, and saline. With a time window of 20 to 25 seconds for the bubbles to appear in the TCD recording and with a sequence of first Echovist and Valsalva maneuver and then Echovist with coughing, all shunts were reliably identified with a specificity of 65% compared with TEE as the traditional gold standard. The time of first microbubble appearance was not helpful to distinguish between shunts detected on TEE and other shunts. CONCLUSIONS TCD performed twice with 2 provocation maneuvers using Echovist is a sensitive method to identify cardiac right-to-left shunts also identified by TEE.

Treatment of Acute Ischemic Stroke With the Low-Molecular-Weight Heparin Certoparin Results of the TOPAS Trial

Background and Purpose— To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]). Methods— We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti–factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index ≥90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration. Results— The proportion of patients with Barthel Index ≥90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed. Conclusions— Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.

Cerebral and Systemic Embolization During Left Ventricular Support With the Novacor N100 Device

BACKGROUND Patients undergoing implantation of left ventricular assist systems (LVAS) are prone to thromboembolic complications. We analyzed the incidence, clinical findings, and outcome of neurologic and systemic thromboembolic events (TE) in patients with the Novacor N100 LVAS. In a subset of patients, transcranial Doppler sonography was used to detect microembolic signals. METHODS Thirty-six patients underwent implantation of a Novacor N100 LVAS for various reasons. The surgical procedure was elective in 18 patients and scheduled on an urgent or emergency basis in another 18 patients. The assist period lasted from 17 to 336 days (109 +/- 88 days); 22 patients were forwarded to heart transplantation after being supported for 140 +/- 87 days. RESULTS Clinical cerebral embolism was evident in 17 patients (47%). Thromboembolic events were singular in 8 and multiple in 9 patients; in the latter up to 10 TE occurred (mean +/- SD, 1.4 +/- 2 TE). Leading neurologic symptoms were unilateral hemiplegia in 11, as well as ocular symptoms and aphasia in 12 patients each. Noncerebral TE were detected in 4 patients, 2 of whom underwent an emergency operation for intestinal and iliac artery occlusion. The incidence of TE did not correlate strongly with the interval of LVAS support. Cerebral computed tomography confirmed lesions in 58% of patients. Transcranial Doppler sonography detected microembolic signals on 67% of all recordings, with the microembolic signals being more frequent on days with clinically manifest TE. The outcomes were good, as only 2 patients suffer from neurologic sequelae. CONCLUSIONS Thromboembolism is still a major threat for patients with LVAS implantation. Neurologic sequelae are frequent but have a favorable prognosis, and systemic complications occur considerably less often. Patient selection, adequate anticoagulation, and transcranial Doppler sonography may help to reduce the incidence of TE.