The amount of solid cerebral microemboli during carotid stenting does not relate to the frequency of silent ischemic lesions.

BACKGROUND AND PURPOSE: Carotid artery stent placement (CAS) may be associated with clinically silent cerebral lesions. We prospectively evaluated the association of the number of solid cerebral microemboli during unprotected CAS with the frequency of silent cerebral lesions as detected by diffusion-weighted MR imaging (DWI). METHODS: We performed multifrequency transcranial Doppler detection of solid microemboli in the ipsilateral middle cerebral artery (MCA) during CAS in 27 consecutive patients with symptomatic high-grade carotid stenoses. No embolus protection was used in any of the cases. DWI before and 24 +/- 2 hours after CAS was used to detect new ischemic lesions. RESULTS: We detected 484 solid microemboli in 17 patients (63%). On MR imaging 24 +/- 2 hours after CAS, 6 patients (22%) had developed 13 new clinically silent DWI lesions within the ipsilateral MCA territory. In patients with Doppler evidence of solid emboli during CAS, the incidence of new DWI lesions was higher (29%) than in patients without Doppler evidence of solid emboli during the procedure (10%); this difference was not statistically significant (P = .25). The number of solid microemboli during CAS in patients with new ipsilateral DWI lesions was not significantly different from that in patients without new ipsilateral DWI lesions. CONCLUSIONS: Solid microembolism is a common event during unprotected CAS; however, the frequency of procedure-related silent cerebral lesions appears to be independent of the number of solid cerebral microemboli during the procedure.

DIAS I: duplex-sonographic assessment of the cerebrovascular status in acute stroke. A useful tool for future stroke trials.

BACKGROUND AND PURPOSE: A number of controlled trials have evaluated the benefit of intravenous thrombolysis in acute stroke with inconsistent results. None of these studies assessed the initial vascular status or provided information regarding the recanalization rate after therapy. Further trials need to clarify whether certain subgroups might possibly benefit more than others from intravenous thrombolysis. Therefore, a fast and valid method for assessment of cerebrovascular status is needed. In this multicenter study, we evaluated the potentials and limitations of color-coded duplex sonography (TCCS) for cerebrovascular status assessment in acute stroke patients before and after therapy. Furthermore, we compared the recanalization rate for patients referred to thrombolytic and conservative medical therapy. METHODS: Fifty-eight patients suffering from hemispheric stroke were enrolled consecutively in 8 centers. Duplex sonography was performed on admission, 2 hours after start of therapy, and 24 hours after onset of symptoms. Therapy was started within 6 hours. RESULTS: Intravenous thrombolysis was performed in 18 patients, conservative medical therapy in 39 patients, and early thromboendarterectomy in 1 patient. The middle cerebral artery (MCA) mainstem was patent in 29 patients (53.7%), occluded in 25 (46.3%), and was not assessable in 4 patients. Recanalization of the occluded MCA after 2 and 24 hours was diagnosed in 50% and 78% of the patients treated with rtPA and in 0% and 8% in the conservatively treated patients. CONCLUSIONS: Intravenous thrombolysis is highly effective in restoring blood flow after MCA occlusion. TCCS is suitable for assessment of the cerebrovascular status in acute stroke and therefore might define therapeutically relevant subgroups of patients in future stroke trials on the basis of their vascular pathology.

An increased frequency of patent foramen ovale in patients with transient global amnesia. Analysis of 53 consecutive patients.

OBJECTIVE: Alerted by the number of patients with transient global amnesia (TGA) in whom Valsalvalike activities immediately preceded the onset of TGA, we have investigated the frequency of patent foramen ovale (PFO) as the prerequisite for paradoxical embolism. DESIGN: Case series with comparison to a control group. SETTING: Hospitalized and ambulatory patients at the neurological departments of the Alfried Krupp Hospital, Essen, Germany, and the Rheinisch-Westfälische-Technische Hochschule, Aachen, Germany. PATIENTS: Fifty-three consecutive patients with TGA were evaluated by the 2 centers between 1988 and 1995. RESULTS: Using contrast transcranial Doppler sonography we have observed a PFO in 55% of the patients with TGA, compared with 27% of a control group of 100 patients. This difference was statistically significant (P < .01). Twenty-five patients with TGA (47%), 15 of them with a proven PFO, reported a precipitating activity, such as the lifting of heavy weights, immediately before the TGA occurred. CONCLUSIONS: In addition to other pathological mechanisms, paradoxical embolism with temporobasal ischemia could possibly play a role in the clinical syndrome of TGA. This hypothesis could explain the frequent observation of preceding Valsalvalike activities in patients with TGA.

Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack.

To evaluate the additional value of transesophageal (TEE) compared with transthoracic (TTE) echocardiography and the role of patent foramen ovale (PFO) and deep vein thrombosis in the work-up of embolic events, patients with presumed cardiac embolic stroke or transient ischemic attack (neurovascular etiology was excluded) were prospectively studied by transthoracic and transesophageal contrast echocardiography. If PFO was detected echocardiographically, PFO size was assessed semiquantitatively and phlebography of both legs was performed. Two hundred forty-two consecutive patients (153 men, 60 +/- 15 years) were studied. In 197 patients, neuroimaging showed evidence of embolic infarction. TEE identified 138 potential cardiac sources of embolism in 111 patients, compared with 69 by TTE (p <0.01) in 59 patients. TEE detected potential cardiac sources in 52 patients with negative TTE examination and was significantly superior compared with TTE for identifying left atrial thrombi, spontaneous echo contrast, PFO, atrial septal aneurysm, and atheroma of the ascending aorta. In patients with a positive TTE, additional diagnostic information by TEE was found in only 6 patients and did not change therapy. Phlebography was performed in 53 patients with PFO and revealed deep vein thrombosis in 5 patients (9.5%); all had medium or large PFOs. Thus, in patients with cerebral ischemia of suspected cardiogenic origin and a normal TTE examination, TEE detects potential causes of embolism in 31% of patients and is therefore of diagnostic relevance. Conversely, in the presence of a diagnostic TTE an additional TEE confers only marginal diagnostic benefit. Deep venous thrombosis was detected in nearly 10% of patients with PFO as the sole identifiable cardiac risk factor. Given that in 4 of 5 patients deep vein thrombosis was clinically silent, phlebography should be performed in patients with medium or large interatrial shunts if paradoxical embolism is suspected.

Intrathecal versus systemic corticosteroids in the treatment of multiple sclerosis: results of a pilot study.

Fifty patients with multiple sclerosis were treated either by corticosteroids given systemically or by intrathecal injection of a steroid crystal suspension. Before and 3 weeks after the beginning of the treatment we examined the patients according to the Expanded Disability Status Scale (EDSS). Four patients had to be excluded from evaluation. In 23 patients the examination revealed at least a small improvement in their disability status. There were 7 intrathecally and 5 systemically treated patients whose disability was significantly reduced. One patient under intrathecal treatment showed a minor deterioration in disability. There was no clear difference in the frequency of improved symptoms or in EDSS scores between the two therapies.

Antenatal betamethasone treatment reduces synaptophysin immunoreactivity in presynaptic terminals in the fetal sheep brain.

Knowledge of morphofunctional effects on the fetal brain induced by exogenous glucocorticoids is limited. Recently, we reported alterations of both the neuronal cytoskeleton and electrocortical function in the ovine fetal brain after antenatal betamethasone treatment in doses used in perinatal medicine. In the present study we examined whether these changes are accompanied by morphological alterations of synapses. Chronically instrumented fetal sheep at 0.87 of gestation were treated either with isotonic saline (n=7) or 10 microg/h betamethasone (n=7) over 48 h administered directly to the fetal jugular vein. Paraffin sections of the frontal neocortex, caudate putamen and hippocampus were stained with a monoclonal antibody against synaptophysin, a specific membrane protein of presynaptic vesicles and quantified morphometrically. Synaptophysin-like immunoreactivity (synaptophysin-LI) showed a widespread granular pattern in the neuropil. Betamethasone exposure reduced synaptophysin-LI in the frontal neocortex, caudate putamen and hippocampus by 46.9, 41.0 and 55.4%, respectively, (P<0.05) that was not accompanied by irreversible neuronal damage. These results suggest that clinical doses of betamethasone have acute effects on presynaptic terminals in the fetal sheep brain that could contribute to the altered complexity of electrocortical function that we have shown previously to occur following fetal exposure to betamethasone.

Detection of stenoses in the anterior circulation using frequency-based transcranial color-coded sonography.

Atherosclerotic stenoses of the intracranial vessels are less frequent than those of the extracranial vessels, but they are associated with a considerable annual stroke rate. The aim of the present study was to investigate the usefulness of frequency-based transcranial color-coded sonography (TCCS), transcranial Doppler sonography (TCD) and digital subtraction angiography (DSA) in patients with middle cerebral artery (MCA) and intracranial internal carotid artery (ICA) stenosis. Forty patients presenting with 48 intracranial stenoses of the anterior circulation were involved in the study. The stenoses were detected in the neurovascular laboratory during routine TCD examinations. All patients underwent an additional frequency-based TCCS examination. Both the axial and coronal planes were obtained to allow the exact localization of MCA stenosis and differentiation from intracranial ICA stenosis. Angle-corrected flow velocity measurements were performed if straight vessel compartments were 20 mm or more in length. A total of 18 stenoses (44%) were investigated additionally with DSA. According to the investigation with TCD, 20 (42%) stenoses were low-grade, 12 (25%) were moderate, and the remaining 16 (33%) were severe. Angle-corrected flow velocity measurements obtained with the integrated pulse-wave Doppler device of the TCCS machine were highly correlated (0.912, p < 0.001) with those obtained with TCD. TCCS achieved a reliable differentiation of MCA main stem stenosis vs. intracranial ICA stenosis in 7 patients and vs. MCA branch stenosis in 4 patients, but TCD failed in these two subgroups. The agreement between DSA and TCCS to evaluate semiquantitatively 18 intracranial stenoses resulted in a weighted-kappa value of 0.764. The major clinically relevant advantages of TCCS over TCD in MCA stenosis are its ability to differentiate MCA trunk stenosis from terminal ICA or MCA branch stenosis reliably and to perform angle-corrected flow velocity measurements.

Origin and appearance of HITS induced by prosthetic heart valves: an in vitro study.

Patients with mechanical heart valve prostheses show significantly enhanced numbers of HITS detected by transcranial Doppler ultrasound. In order to assess the origin of HITS formation, an in vitro study was set out to quantify valve induced microemboli for mechanical and bioprosthetic valves under various circulatory conditions by means of Ultrasound-Doppler-Sonography. At the same time the influence of CO2 partial pressure on HITS rate vas investigated. It can be summarised that for mechanical heart valve prostheses a strong correlation exists between left ventricular dp/dtmax and the detected HITS rates. It was also demonstrated that a bioprosthesis generates significantly less HITS than a mechanical valve. The origin of HITS is gaseous since the tests were carried out using a cell-free filtered water-glycerol test fluid. The HITS rate could be increased by increasing the amount of dissolved gas within the test fluid. The results support the hypothesis that cavitation is the key factor in the appearance of gaseous microemboli at heart valve prostheses.

Cerebral emboli in cryptogenic ischemia: a reason to enforce diagnostic testing.

BACKGROUND: Stroke of unknown origin is a diagnostic and therapeutic challenge. A subgroup-analysis was performed to evaluate microembolus detection in these cryptogenic strokes. METHODS AND RESULTS: In this study, 78 patients with acute cerebral ischemia in the anterior circulation were monitored for microembolic signals (MES) by the use of transcranial doppler at admittance and 2 times at 24-hour intervals. All patients underwent routine stroke work-up. Twenty patients presented with cryptogenic ischemia. Of these 20 patients, 30% (6/20) showed MES during examination 1, 20% (4/20) in examination 2, and 20% (4/20) in examination 3. CONCLUSION: MES could be detected in 45% of patients with cryptogenic ischemia. Thus, the underlying pathology may be in part embolic. The detection of MES in cryptogenic ischemia should therefore be an argument for extensive retesting to maybe identify a potential embolic source.

Effects of sustained low-level elevations of carbon dioxide on cerebral blood flow and autoregulation of the intracerebral arteries in humans.

Cerebral blood flow velocity (CBFv) was measured by insonating the middle cerebral arteries of four subjects using a 2 Mhz transcranial Doppler. Ambient CO2 was elevated to 0.7% for 23 d in the first study and to 1.2% for 23 d in the same subjects in the second study. By non-parametric testing CBFv was elevated significantly by +35% above pre-exposure levels during the first 1-3 d at both exposure levels, after which CBFv progressively readjusted to pre-exposure levels. Despite similar CBFv responses, headache was only reported during the initial phase of exposure to 1.2% CO2. Vascular reactivity to CO2 assessed by rebreathing showed a similar pattern with the CBFv increases early in the exposures being greater than those elicited later. An increase in metabolic rate of the visual cortex was evoked by having the subjects open and close their eyes during a visual stimulus. Evoked CBFv responses measured in the posterior cerebral artery were also elevated in the first 1-3 d of both studies returning to pre-exposure levels as hypercapnia continued. Cerebral vascular autoregulation assessed by raising head pressure during 10 degrees head-down tilt both during the low-level exposures and during rebreathing was unaltered. There were no changes in the retinal microcirculation during serial fundoscopy studies. The time-dependent changes in CO2 vascular reactivity might be due either to retention of bicarbonate in brain extracellular fluid or to progressive increases in ventilation, or both. Cerebral vascular autoregulation appears preserved during chronic exposure to these low levels of ambient CO2.

Transcranial grey-scale sonography of subdural haematoma in adults.

AIM: Transcranial high-resolution grey-scale sonography reliably allows diagnosis and monitoring of subdural haematoma (SDH) and extra-cerebral intracranial fluid collections in infants but has not been evaluated thoroughly in adults up to now. Because of rapid development of ultrasound systems, the depiction of intracerebral haemorrhage (ICH) has now become feasible. The presented study evaluated the sonographic appearance of SDH in adults. METHOD: We performed transcranial grey-scale sonography (TGS) in 25 consecutive patients with SDH confirmed by cranial computed tomography (CCT) or MRI. According to paediatric TGS, the dural border of the arachnoid was depicted as a highly echogenic membrane, and the distance between the skull and the echogenic membrane was measured. SDH was measured by CCT/MRI and by TGS in corresponding axial planes. The rate of identification of SDH in TGS was evaluated, and the extent of SDH as assessed by CCT/MRI and TGS was compared. RESULTS: TGS reliably detected SDH in 22 of the 25 patients with confirmed SDH (88 %). In the remaining 3 patients, the temporal bone window was insufficient for TGS investigation. Extent of SDH measured by CCT and TGS correlated linearly (r= 0.849). CONCLUSION: TGS allows imaging of SDH in patients with CCT/MRI confirmed SDH, and the extent of SDH correlates significantly between TGS and CCT/MRI. Therefore, TGS may be a possible alternative to serial CCT imaging in monitoring SDH, since in contrast to CCT, TGS is a non-invasive bedside method. So far, TGS is not suitable for the diagnosis of SDH.

[Diplopia and cardiogenic shock]. / Doppelbilder und kardiogener Schock. Eine okuläre Myositis assoziiert mit einer Riesenzellmyokarditis.

Idiopathic giant cell myocarditis is a rare and frequently fatal inflammatory heart disease which leads to congestive heart failure or ventricular arrhythmias. It is often associated with other autoimmune disorders. We report a 39-year-old woman who first presented with diplopia and painful eye movements, the typical clinical picture of orbital myositis. Shortly afterwards, she developed rapidly progressive congestive heart failure due to giant cell myocarditis, which took a fatal course within some weeks. Autopsy confirmed both disorders. This case report underlines the importance of early and repeated monitoring of cardiac function, if orbital myositis is suspected, in order to consider cardiac transplantation, the only efficacious treatment of giant cell myocarditis, in time.

Clinical correlations of Doppler microembolic signals in patients with prosthetic cardiac valves: analysis of 580 cases.

BACKGROUND: The clinical relevance of Doppler microembolic signals (MES) in patients with prosthetic cardiac valves was evaluated by merging and statistically reanalyzing patient data from four research institutions (Departments of Neurology, Universities of Aachen, Halle, and Münster, Germany; Department of Medicine and Therapeutics, University of Glasgow, Scotland, and Department of Cardiothoracic Surgery, Western Infirmary, Glasgow, Scotland). METHODS: Transcranial Doppler monitoring for MES was performed over the middle cerebral arteries for 30 to 60 minutes per patient. Prevalence of neurological complications was evaluated with a standard neurological questionnaire in patients carrying the valve implant longer than 3 months (n=369). RESULTS: Significant differences in MES prevalence and counts were noted among the 580 patients depending on valve type (presented with medians and [95% confidence intervals]): St Jude Medical, n=200, 72%, 4 [3 to 6]; Björk Shiley Monostrut, n=99, 92%, 133 [93 to 181]; Medtronic Hall, n=80, 47%, 1 [2 to 5]; ATS, n=61, 52%, 3 [2 to 5]; Tecna, n=38, 71%, 2 [1 to 4]; Carbomedics, n=37, 81%, 8 [5 to 13]; Carpentier-Edwards supraannular, n=54, 39%, 1 [0 to 3]; Sorin biological, n=11, 9%, 0 [0 to 0]. No relation between MES counts and valve size, international normalized ratio, patients' age, cardiac rhythm, or implant duration was noted. No significant differences in MES counts or prevalence (22 [3 to 68] versus 5 [3 to 6] and 63% versus 69%, both P>.05), in valve duration, valve position, valve type, patients' age, sex, cardiac rhythm, or international normalized ratio were evident between neurologically symptomatic (n=42) and asymptomatic patients. CONCLUSIONS: MES in patients with prosthetic cardiac valves depend on the type and, in certain valve types, the position of the valve implant and possess no direct clinical significance.

[Unusual manifestation of zoster sine herpete as unilateral caudal cranial nerve syndrome]. / Ungewöhnliche Manifestation eines Zoster sine herpete als unilaterales kaudales Hirnnervensyndrom.

Multiple lower cranial nerve palsies are a rare complication following varicella zoster virus (VZV) reactivation, especially if typical herpetic eruptions are lacking. We report a case of a 45-year-old, immunocompetent male with unilateral involvement of the cranial nerves VIII, IX, X, and XI without skin lesions. Cerebrospinal fluid (CSF) studies revealed mononuclear pleocytosis with intrathecal antibody synthesis against VZV, while polymerase chain reaction (PCR) did not detect VZV or HSV (herpes simplex virus). The patient almost completely recovered after aciclovir administration. VZV reactivation without rash (zoster sine herpete) may lead to multiple cranial nerve palsies. PCR is a useful tool to detect VZV-DNA in CSF, but negative results do not exclude a reactivation. In case of multiple cranial nerve palsies of unknown etiology with mononuclear pleocytosis in CSF tumors of the skull base, meningitis tuberculosis, and meningeosis have to be excluded, and antiviral therapy should be discussed.

[The value of duplex sonography in cerebral ischemia]. / Die Bedeutung der Duplexsonographie bei zerebralen Ischämien.

Doppler color flow imaging (DCFI) is a new ultrasound technique for the assessment of extracranial arterial disease. This system is a further development of conventional duplex systems. The new technique provides a real-time gray-scale echotomogram (B-mode) and simultaneously superimposed color-coded Doppler signals of intravascular blood flow. The advantages of the DCFI are improved identification of vascular structures, faster data acquisition, shorter examination time, better characterization of the surface, structure and extent of plaques with easier detection of ulcerative lesions or thrombotic material. Due to these advantages, the sensitivity for the detection of lesions which may cause arterio-arterial embolisms to the brain, is increased. With DCFI, it is possible to visualize the extracranial portion of the vertebral arteries. This improves the evaluation of the vertebro-basilar circulation. DCFI is a safe and fast method in the follow-up procedure of symptomatic and asymptomatic patients and after carotid endarterectomy. Using DCFI, the interaction between morphology and hemodynamics in the extracranial vessels can be analyzed, which is important particularly for the understanding of the potential risk of different plaque types.

Evidence for embolization from a posterior cerebral artery thrombus by transcranial Doppler monitoring.

BACKGROUND: Transcranial Doppler monitoring enables the detection of emboli passing through intracranial arteries. Comparison of the different intracranial vessels with respect to emboli detection can be of use in identifying the source of embolism. CASE DESCRIPTION: We report the case of a patient with an acute posterior cerebral artery (PCA) infarct on the right side, with evidence for high-degree ipsilateral PCA narrowing on admission. During transcranial Doppler monitoring 3 days later, we found frequent emboli-like signals in the power spectrum of the right PCA distal to the stenosis but not in any other intracranial vessels. Four days later, angiography and transcranial Doppler failed to show PCA narrowing, and transcranial Doppler monitoring of the right PCA showed no further emboli-like signals. A stenosis of the right vertebral artery was regarded as the possible source of thromboembolic narrowing of the PCA. CONCLUSIONS: We assume that in our patient a thrombotic clot in the PCA was resolved autolytically through detachment of small emboli into the distal part of the PCA. We speculate that in the early course of autolysis a larger fragment of the clot had occluded one of the distal branches, thus leading to the small PCA territory infarct.

High-grade stenosis of the internal carotid artery assessed by color and power Doppler imaging.

PURPOSE: Visualization of carotid artery stenosis is important to improve our understanding of the etiology of ischemic stroke. Two sonographic methods are available for visualizing carotid stenosis: power Doppler imaging (PDI) and color Doppler imaging (CDI). The purpose of this study was to compare the advantages and limitations of these methods in the evaluation of internal carotid artery (ICA) stenosis. METHODS: Thirty-two patients with at least 70% extracranial ICA stenosis were included in this prospective study. All subjects were examined with CDI and PDI. Four criteria were used to evaluate diagnostic accuracy and overall efficacy: identifying the target vessel, determining the causal pathology, evaluating blood flow, and the examiner's confidence in the diagnosis. RESULTS: All patients had high-grade stenosis (17 patients had 70% stenosis, 11 had 80%, 2 had 90% and 2 had pseudo-occlusions of the ICA). PDI was significantly (p < 0.05) superior to CDI in identifying the target vessel and highly significantly (p < 0.01) superior to CDI in evaluating blood flow. There were no significant differences between CDI and PDI in determining the causal pathology or in the examiner's confidence in the diagnosis. CONCLUSIONS: This study demonstrates that PDI is a good additional method to CDI and should be used with it to evaluate ICA stenosis.

Oculo-bulbar myasthenia gravis induced by cytokine treatment of a patient with metastasized renal cell carcinoma.

OBJECTIVE: The occurrence of autoimmune diseases or deterioration of pre-existing disorders has recently been described after cytokine treatment. The present report gives evidence for acquired myasthenia gravis induced by externally administered interferon-alpha and interleukin-2 in a patient with metastasized renal cell carcinoma. Electromyographic investigations did not reveal generalised myasthenia gravis. However, a highly elevated titre of antibodies against the human acetylcholine receptor and a significant improvement in clinical symptoms during therapy with anticholinesterase drugs, combined with a decremental response in electronystagmography, indicated an intermittent mainly oculo-bulbar form of myasthenia gravis.

Agenesis of the internal carotid artery: color Doppler, CT, and MR angiography findings.

Agenesis of the internal carotid artery (ICA) is a rare finding that can lead to the false diagnosis of an ICA occlusion. We present the case of a young woman with agenesis of the left ICA. Diagnosis was made noninvasively by color Doppler imaging (CDI) in combination with high-resolution CT of the base of the skull. Magnetic resonance angiography confirmed the diagnosis. CDI in combination with CT of the base of the skull allows the diagnosis of ICA agenesis without the use of invasive procedures.