Sonothrombolysis: experimental evidence.

Reopening of the occluded artery is the primary therapeutic goal in hyperacute ischemic stroke. Systemic treatment with tissue recombinant plasminogen activator (tPA) has been shown to be beneficial at least in a 3-hour door to needle window. Intra-arterial thrombolysis is favorable and opens the window of treatment up to at least 6 h but consequences invasive intra-arterial angiography in a high number of patients, of whom a significant number do not finally receive thrombolysis. The combination of ultrasound with thrombolytic agents may enhance the potential benefit by means of enzyme-mediated thrombolysis. When ultrasound is applied externally through skin or chest, attenuation will be very low. Attenuation, however, is significantly higher if penetration through the skull is required. Attenuation is frequency dependent, with ultrasound intensity being <10% of the output intensity for diagnostic frequencies (>1 MHz). This ratio nearly reverses in the kiloHertz range (>500 kHz). Ultrasound insonation is efficient for accelerating enzymatic thrombolysis within a wide range of intensities, from 0.5W/cm2 (MI approximately 0.3) to several watts per square centimeter, particularly in the nonfocused ultrasound field. Insonation with ultrasound increased tPA-mediated thrombolysis up to 20% in a static model, while it enhanced the recanalization rate from 30 to 90% in a flow model. Results from embolic rat models suggest that low-frequency ultrasound with 0.6W/cm2 significantly reduces infarct volume compared to pure tPA treatment. Safety of ultrasound exposure of the brain for therapeutic purposes has to address hemorrhage, heating, and direct tissue damage. Since animal studies suggested no increase of bleeding rate or harm to the blood-brain barrier, a clinical phase II study applying low-frequency ultrasound at approximately 300 kHz found a high number of secondary hemorrhages. Heating depends critically on the characteristics of the ultrasound. The most significant heating of the brain tissue itself is >1 degrees C per hour using a 2W/cm2 probe; however, no significant heating could be found when using an emission protocol pulsing the ultrasound. The current experimental data helps to identify the optimal ultrasound characteristics for sonothrombolysis and supports the hypothesis combined treatment being a perspective in optimizing thrombolytic therapy in acute stroke.

Acute stroke: therapeutic transcranial Doppler sonography.

Ultrasound (US) has emerged as a new tool to treat ischemic stroke. The potential advantage of US is decreased risk of systemic bleeding complications due to its site-specific effect. Moreover, external application is noninvasive and is readily available. Experimental studies showed that low intensity (

Acute stroke: therapeutic transcranial color duplex sonography.

The enhancement of thrombolysis by ultrasound energy (sonothrombolysis) is an emerging field of interest in the treatment of acute ischemic stroke. Recent in vitro and clinical studies have investigated the effects of using transcranially applied 'diagnostic' ultrasound for this purpose. Using transcranial color duplex sonography (TCDS) allows an examiner to identify the site of occlusion and focus the ultrasound beam on it. Clinical studies using TCDS to enhance thrombolysis in acute middle cerebral artery occlusions have revealed an accelerating effect on recanalization, as well as a tendency for a better outcome. Data from small sample studies suggest that this effect on recanalization is present not only in combination with recombinant tissue plasminogen activator (rt-PA), but also with any thrombolytic drug. However, when TCDS was used in combination with rt-PA, an increase in the rate of asymptomatic and symptomatic intracerebral hemorrhages tended to occur compared to patients treated with thrombolysis alone. Larger sample-sized clinical studies should be conducted in the future to evaluate the safety and efficacy of using TCDS for sonothrombolysis. This method should also be further developed to determine its effect when used in combination with other types of ultrasound and thrombolytic drugs.

[Headache in patients with cerebral venous thrombosis]. / Céphalées au cours des thromboses veineuses cérébrales.

Headache is the most frequent symptom of cerebral venous thrombosis. They do not have particular characteristics and can mimic other numerous varieties of headache. Frequently associated with other neurological symptoms, such as intracranial hypertension, seizures, focal deficits or disorders of consciousness, they are sometimes isolated, which stresses the need for investigations in all recent and unusual headache.

Bilateral paramedian thalamic contrast enhancement on CT after Intra-arterial thrombolysis.

A 58-year-old woman presented with an acute embolic occlusion of the distal basilar artery. She underwent angioplasty and intra-arterial thrombolysis. Angiography performed after recanalization revealed a single perforating thalamic artery. A nonenhanced CT scan carried out immediately after the procedure revealed hyperdense lesions in the bilateral paramedian portions of the thalami, which disappeared on the 24-hour follow-up CT scan. Three months later, the patient improved to functional independence, but had some memory dysfunction and vertical gaze palsy. This case suggests that contrast enhancement or extravasation can occur in the thalamus after intra-arterial thrombolysis performed to recanalize a basilar artery occlusion.

Quantitative EEG monitoring during cerebral air embolism and hyperbaric oxygen treatment in a pig model.

The purpose of this study was to evaluate the contribution of quantitative EEG (qEEG) to an animal model of cerebral air embolism (CAE). In 12 anesthetized pigs, air was injected into the internal carotid artery, and hyperbaric oxygen (HBO) treatment was started either after 3 minutes or after 60 minutes (United States Navy Treatment Table 6). Off-line spectral analysis was used to determine the frequency content of the EEG signal, and factor analysis was performed to determine the frequency ranges that optimally showed the changes in the power spectrum. Factor analysis revealed two factors that represented different and independent spectral changes during embolization: 0.5 to 7.3 Hz (band 1) and 26.4 to 30.3 Hz (band 2). Shortly after embolization, the power in both bands decreased to a minimum, representing an isoelectric EEG in 11 out of the 12 animals. EEG differences between animals were considerable, despite standardized doses of injected air, and qEEG can objectively assess and quantify these differences in immediate impact of air embolism on brain function. Also, qEEG enabled monitoring of the recovery from the initial embolic event and of the response on treatment. The initial recovery was much more protracted in band 2 than in band 1, but even after completing HBO treatment, qEEG values did not return to baseline values in all animals. In addition, two animals did not survive until the end of the HBO treatment, and qEEG proved to be superior to the other measured hemodynamic variables to detect and ensure a deterioration of brain function. This study showed that qEEG monitoring has significant additional value to monitoring HBO treatment.

[Serious cerebral venous thrombosis: can we use fibrinolytic?]. / Thrombophlébite cérébrale grave: peut-on fibrinolyser ?

We report a case of thrombosis of superior sagittal and cavernous sinuses treated by direct instillation of fibrinolytic agents via selective catheterization. Despite risk of bleeding related to the pathology and treatment, no adverse side-effect occurred. This report is unusual regarding the poor initial clinical patient's condition with dilated and unreactive pupil. The good neurologic outcome warrants aggressive treatment in the most severe forms of cerebral venous thrombosis.

Endovascular therapy of acute vertebrobasilar occlusion: early treatment onset as the most important factor.

In view of the poor prognosis for patients with acute intracranial vertebrobasilar occlusion (VBO), factors were sought that predict survival and good neurologic outcome after acute endovascular treatment by means of local intra-arterial fibrinolysis (LIF) and percutaneous transluminal angioplasty (PTA). LIF was performed in 83 patients with angiographically established acute VBO. A significant residual stenosis after LIF was treated by additional PTA in 8 patients. The types of occlusion were classified as either embolic occlusion (EO) or atherothrombotic occlusion (AO). Outcome was evaluated after 3 months by the Barthel Index (BI) as favorable (BI >90), unfavorable (BI <90) or death and compared for each of 3 diagnostic or treatment variables: recanalization success, occlusion type and time to treatment. Four fibrinolytic treatment modes [urokinase, low-dose and high-dose recombinant tissue-type plasminogen activator (rt-PA), rt-PA + Lys-plasminogen] were also analyzed. The outcome was favorable in 19 patients (23%), unfavorable in 14 (17%) and 50 died (60%). Recanalization was successful in 54 patients (66%). The neurologic outcome was better in recanalized than in nonrecanalized patients (favorable outcome: 30 vs. 10%, mortality: 54 vs. 72%; p = 0.118). The neurologic outcome was better in EO than in AO (favorable outcome: 31 vs. 17%, mortality: 47 vs. 70%, p = 0.112). Under combined treatment by LIF and PTA in 8 patients with AO, 4 survived, 3 with a favorable outcome (38%). Early treatment onset (6 h; favorable outcome: 36 vs. 7%, mortality: 52 vs. 70%, p = 0.005). Although no statistically significant differences were found between the types of fibrinolytic agents, treatment with rt-PA and Lys-plasminogen tended toward better results. Early treatment onset proved to be the most important factor for successful endovascular therapy in acute VBO, whereas recanalization and presence of an embolic occlusion also tended toward better results. Additional PTA may be a promising therapy in cases of significant residual stenosis after LIF.

Combination of early and delayed SPET imaging using technetium-99m ethyl cysteinate dimer immediately after local intra-arterial thrombolysis.

The aim of this study was to investigate the prognostic utility of post-treatment technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission tomography (SPET) for predicting ischemic tissue outcome in cases involving embolic middle cerebral artery occlusion treated with local intra-arterial thrombolysis. We examined twenty-five patients with a moderately ischemic area determined using pretreatment technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) SPET, and with complete recanalization within 6 h. Post-treatment 99mTc-ECD SPET studies, consisting of scanning for 0.5-6.5 min (early scan) and 15-21 min (delayed scan) after tracer injection, were performed immediately after thrombolysis. The extent of the affected area outlined on pretreatment 99mTc-HMPAO SPET was used for the post-treatment early and delayed 99mTc-ECD SPET images, and the AR/CE ratio (ratio of affected regional activity to cerebellar activity) was calculated. The washout index of 99mTc-ECD in the affected area was also calculated by dividing the difference between the AR/CE ratio in the early and delayed images by the AR/CE ratio in the early image. Twelve patients without infarction or with small subcortical/basal ganglial infarction, ten with medium or large cortical infarction, and three with hemorrhage were identified by follow-up computed tomography. Although the AR/CE ratio in post-treatment early 99mTc-ECD SPET images was significantly higher in the hemorrhagic group than in the cortical infarction group, this value did not differentiate the reversible ischemia group from either the cortical infarction or the hemorrhagic group. The AR/CE ratio in post-treatment delayed 99mTc-ECD SPET images statistically differentiated the reversible ischemia group from both the cortical infarction and the hemorrhagic group. However, the difference between the cortical infarction and hemorrhagic groups was not statistically significant. The washout index of 99mTc-ECD statistically differentiated all three groups. This study demonstrated that a combination of early and delayed 99mTc-ECD SPET imaging performed immediately after thrombolysis predicts ischemic tissue outcome.

Doença cérebro-vascular cardiogênica / Cardiogenic cerebrovascular disease: a review

A coexistência de doença cardíaca e doença cérebro-vascular é conhecida há longa data. Autópsias revelam que infarto cerebral está presente em mais de metade dos pacientes que morrem de doença cardíaca. Além disso, isquemia cerebral é secundária a evento cardio-embólico em aproximadamente 20 por cento dos casos. Em virtude disso, os autores fazem uma revisão na literatura sobre etiologias de doença cérebro-vascular, discutindo sua fisiopatologia, mecanismos diagnósticos e tratamento

Uso de anticoagulantes en la fase aguda del infarto cerebral / Antithrombotic therapies in acute cerebral stroke

El uso óptimo de antitrombóticos en la fase aguda del infarto cerebral puede prevenir la recurrencia y progresión de la isquemia. En el caso de anticoagulación, su uso continua siendo controvertido debido a que hasta ahora no se ha establecido la seguridad y/o efectividad. Investigaciones recientes en cuanto a otras alternativas terapéuticas con similares características antitrombóticas, pero con menor propensión a sangrados o trombocitopenia, han llevado al desarrollo de heparinas de bajo peso molecular y de heparinoides. Se revisan las implicaciones terapéuticas de estos estudios, las potenciales indicaciones de anticoagulación en la fase aguda del infarto cerebral y la nueva información disponible en relación con el tema

Liquid jets, accelerated thrombolysis: a study for revascularization of cerebral embolism.

A prior study has reported that a rapid recanalization therapy of cerebral embolism, using liquid jet impacts generated by the interaction of gas bubbles with shock waves, can potentially penetrate through thrombi in as little as a few microseconds with very efficient ablation (Kodama et al. 1997). The present study was undertaken to examine the liquid jet impact effect on fibrinolysis in a tube model of an internal carotid artery. First, the conditions for generating the maximum penetration depth of liquid jets in the tube were investigated. Gelatin was used to mimic thrombi. The shock wave was generated by detonating a silver azide pellet weighing about a few micrograms located in a balloon catheter. The collapse of the inserted gas bubbles and the subsequent liquid jet formation were recorded with high-speed photography. Second, thrombi were formed using fresh human blood from healthy volunteers. The fibrinolysis induced by the liquid jet impact with urokinase was explored. This was conducted under selected conditions based on the experiment using the gelatin. Fibrinolysis was calculated as the percentage of the weight loss of the thrombus. Fibrinolysis with urokinase alone and with a single liquid jet impact with urokinase was 1.9 +/- 3.7% (n = 16) and 20.0 +/- 9.0% (n = 35), respectively, for an incubation time of 60 min. Statistical differences were obtained between all groups (ANOVA). These results suggest that liquid jet impact thrombolysis has the potential to be a rapid and effective therapeutic modality in recanalization therapy for patients with cerebral embolism and other clinical conditions of intra-arterial thrombosis.

Effects of electro-acupuncture on somatostatin and pancreatic polypeptide in ischemic cerebrovascular diseases.

The levels of somatostatin (SS) in CSF and blood and pancreatic polypeptide (PP) in plasma were measured by radioimmunoassay in 64 patients with acute ischemic cerebrovascular diseases (ICVD), randomly divided into two groups: group 1 (n = 31, both electro-acupuncture and routine treatments given) and group 2 (n = 33, routine treatment) and 26 non-ICVD patients were used as controls. The points of electro-acupuncture were Quchi (LI 12), Waiguan (SJ 5) and Huantiao (GB 30) and Zusanli (St 36). After a course of treatment, the SS levels in plasma and CSF were significantly increased in the patients of group 1 with good result and their plasma PP level had no significant change. In the patients with poor result, however, the PP level was significantly decreased. The results suggested that electro-acupuncture might play an active role in alleviating the SS metabolic disturbance in CNS of ICVD patients.

Cerebral arterial gas embolism in air force ground maintenance crew--a report of two cases.

Two cases of cerebral arterial gas embolism (CAGE) occurred after a decompression incident involving five maintenance crew during a cabin leakage system test of a Hercules C-130 aircraft. During the incident, the cabin pressure increased to 8 in Hg (203.2 mm Hg, 27 kPa) above atmospheric pressure causing intense pain in the ears of all the crew inside. The system was rapidly depressurized to ground level. After the incident, one of the crew reported chest discomfort and fatigue. The next morning, he developed a sensation of numbness in the left hand, with persistence of the earlier symptoms. A second crewmember, who only experienced earache and heaviness in the head after the incident, developed retrosternal chest discomfort, restlessness, fatigue and numbness in his left hand the next morning. Both were subsequently referred to a recompression facility 4 d after the incident. Examination by the Diving Medical Officer on duty recorded left-sided hemianesthesia and Grade II middle ear barotrauma as the only abnormalities in both cases. Chest X-rays did not reveal any extra-alveolar gas. Diagnoses of Static Neurological Decompression Illness were made and both patients recompressed on a RN 62 table. The first case recovered fully after two treatments, and the second case after one treatment. Magnetic resonance imaging (MRI) of the brain and bubble contrast echocardiography performed on the first case 6 mo after the incident were reported to be normal. The second case was lost to follow-up. Decompression illness (DCI) generally occurs in occupational groups such as compressed air workers, divers, aviators, and astronauts. This is believed to be the first report of DCI occurring among aircraft's ground maintenance crew.

Neurological complications of cardiac surgery: the need for new paradigms in prevention and treatment.

Neurological injury is a devastating complication of cardiac surgery that results in a longer duration of hospitalization, increased costs, and increased likelihood of death. Such injury can affect any level of the central nervous system, and its manifestations are broad, ranging from neurocognitive dysfunction to frank stroke. Many variables have been found to be indicative or risk for perioperative neurological injury, but the predictive models are more useful for stroke risk than for neurocognitive dysfunction. Strategies aimed at reducing neurological injury during cardiac surgery have focused, for the most part, on the technical aspects of cardiopulmonary bypass. The concomitant performance of carotid endarterectomy and cardiac surgery continues to be controversial, although the management of patients with symptomatic carotid stenosis is better defined. Cerebral embolism, including atheroembolism from the ascending aorta, has an important role in the pathogenesis of neurological injury of all types. Epiaortic ultrasound imaging of the aorta is a sensitive technique for the identification of atherosclerosis of the ascending aorta at the time of surgery, which can allow it to be avoided and therefore reduce the risk for atheroembolism. Results of laboratory investigations have provided insight into the mechanisms of ischemic neuronal injury and a basis for the development of neuroprotective drugs. Neuroprotection may best be accomplished during cardiac surgery because, in contrast to nonsurgical situations, potential agents can be administered before the neurological insult occurs. Reducing the incidence of perioperative stroke will require a multidisciplinary approach that includes novel diagnostic and therapeutic strategies.