Cerebral Air Embolism after Esophagogastroduodenoscopy: Insight on Pathophysiology, Epidemiology, Prevention and Treatment.

BACKGROUND: Air embolism is an extremely rare complication that can follow gastrointestinal endoscopy. The most accepted treatment of cerebral air embolism (CAE) is hyperbaric oxygen (HBO). Limited evidence suggests that lidocaine may have a neuroprotective effect. The exact mechanism does not appear to be well elucidated. METHODS: We conducted a literature search using multiple combinations of keywords from PubMed and Ovid Medline databases according to the PRISMA guidelines. We included articles with cases of air embolism caused by an esophagogastroduodenoscopy (EGD). We excluded cases related to other procedures e.g. colonoscopy, endoscopic retrograde cholangiopancreatography, cholangioscopy, Kasai procedure, bronchoscopy, laparoscopy or thoracoscopy. We were able to identify 30 cases of CAE associated with EGD. We included our experience in treating one patient with CAE after elective EGD. RESULTS: Given the results of our literature search and this patient's characteristics, we chose to treat our patient with HBO and lidocaine infusion. Our case series consists of 31 patients of post EGD CAE, the mean age was 63.7 ± 11.14 years, 38.7% of the patients were women (n = 12). 38.7% of the cases underwent esophageal dilatation (n = 12), while 19.35% had EGD biopsy (n = 6), 9.6% had variceal ligation (n = 3), and 3.22% had variceal banding (n = 1). In 20 out of 31 cases, echocardiography has been documented, 20% of those patients (n = 4) had patent foramen ovale. HBO was used in treatment of 48% of cases (n = 15), among the included patients, 61% survived (n = 19). Our patient showed significant neurological improvement. CONCLUSIONS: Despite the rare incidence of CAE during or after EGD, physicians should be aware of this potential complication. In patients who develop sudden acute neurological symptoms, early diagnosis and intervention may prevent devastating neurological injury and death. The most accepted emergent treatment for CAE includes HBO, consideration of lidocaine, and work-up of source of the air embolism.

A rabbit model of cerebral microembolic signals for translational research: preclinical validation for aspirin and clopidogrel.

UNLABELLED: Essentials Microembolic signal (MES) is an independent predictor of stroke risk in patients. A rabbit model of cerebral microembolic signals was established. Therapeutic efficacy was demonstrated for aspirin and clopidogrel on microembolic signals. Potential translational value of this preclinical model of MES was demonstrated. SUMMARY: Objectives Cerebral microembolic signals (MESs) detected by transcranial Doppler (TCD) ultrasound constitute an independent predictor of stroke risk and prognosis. The aim of this study was to develop a novel preclinical model of MESs to facilitate translational research. Methods A clinical TCD ultrasound machine was used to detect MESs in the cerebral circulation of New Zealand White rabbits. Technical feasibility was assessed for the measurement of MESs in the middle cerebral artery (MCA) by TCD. FeCl3 -induced carotid arterial thrombosis was optimized for the generation of endogenous microemboli. Ascending doses of two antithrombotic agents (aspirin and clopidogrel) were evaluated individually and in combination for their effects on both arterial thrombosis and MESs in a 30% FeCl3 -induced carotid arterial thrombosis model, along with ex vivo functional assays. Results Dose-dependent FeCl3 -induced arterial thrombosis studies showed that 30% FeCl3 resulted in the most consistent and reproducible MESs in the MCA (3.3 ± 0.7 MESs h(-1) ). Ascending-dose studies showed that the effective doses for 50% inhibition (ED50 ) of thrombus formation, based on integrated blood flow and thrombus weight, respectively, were 3.1 mg kg(-1) and 4.2 mg kg(-1) orally for aspirin, and 0.3 mg kg(-1) and 0.28 mg kg(-1) orally for clopidogrel. The ED50 values for MES incidence were 12.7 mg kg(-1) orally for aspirin, and 0.25 mg kg(-1) orally for clopidogrel. Dual treatment with aspirin (5 mg kg(-1) ) and clopidogel (0.3 mg kg(-1) ) resulted in significant reductions in cerebral MESs (P < 0.05) as compared with monotherapy with either agent. Conclusions Our study demonstrated the successful establishment of the MES model in rabbits, and it may provide translational value for MESs and ischemic stroke research.

Hyperbaric oxygen does not improve cerebral function when started 2 or 4 hours after cerebral arterial gas embolism in swine.

OBJECTIVE: Hyperbaric oxygenation is the accepted treatment for cerebral arterial gas embolism. Although earlier start of hyperbaric oxygenation is associated with better outcome, it is unknown how much delay can be tolerated before start of hyperbaric oxygenation. This study investigates the effect of hyperbaric oxygenation on cerebral function in swine when initiated 2 or 4 hours after cerebral arterial gas embolism. DESIGN: Prospective interventional animal study. SETTING: Surgical laboratory and hyperbaric chamber. SUBJECTS: Twenty-two Landrace pigs. INTERVENTIONS: Under general anesthesia, probes to measure intracranial pressure, brain oxygen tension (PbtO2), and brain microdialysis, and electrodes for electroencephalography were placed. The electroencephalogram (quantified using temporal brain symmetry index) was suppressed during 1 hour by repeated injection of air boluses through a catheter placed in the right ascending pharyngeal artery. Hyperbaric oxygenation was administered using U.S. Navy Treatment Table 6 after 2- or 4-hour delay. Control animals were maintained on an inspiratory oxygen fraction of 0.4. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure increased to a mean maximum of 19 mm Hg (SD, 4.5 mm Hg) due to the embolization procedure. Hyperbaric oxygenation significantly increased PbtO2 in both groups treated with hyperbaric oxygenation (mean maximum PbtO2, 390 torr; SD, 177 torr). There were no significant differences between groups with regard to temporal brain symmetry index (control vs 2-hr delay, p = 0.078; control vs 4-hr delay, p = 0.150), intracranial pressure, and microdialysis values. CONCLUSIONS: We did not observe an effect of hyperbaric oxygenation on cerebral function after a delay of 2 or 4 hours. The injury caused in our model could be too severe for a single session of hyperbaric oxygenation to be effective. Our study should not change current hyperbaric oxygenation strategies for cerebral arterial gas embolism, but further research is necessary to elucidate our results. Whether less severe injury benefits from hyperbaric oxygenation should be investigated in models using smaller amounts of air and clinical outcome measures.

Neonatal stroke.

Neonatal stroke encompasses a range of focal and multifocal ischaemic and haemorrhagic tissue injuries. This review will concentrate on focal brain injury that occurs as a consequence of arterial infarction, most frequently the left middle cerebral artery, or more rarely as a consequence of cerebral sinus venous thrombosis (CSVT). Both conditions are multifactorial in origin. The incidence of both acquired and genetic thrombophilic disorders in both mothers and infants is high although rarely causal in isolation. Neurodevelopmental morbidity occurs in over 50% of children. Specific therapy in the form of anticoagulation is currently only recommended in CSVT and needs to be carefully monitored in the presence of haemorrhage.

A novel embolic model of cerebral infarction and evaluation of Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a novel fungal triprenyl phenol metabolite.

The aim of the present study was to establish a novel embolic model of cerebral infarction and to evaluate the effect of Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a novel fungal triprenyl phenol metabolite. Thrombotic occlusion was induced by transfer of acetic acid-induced embolus into the brain. The regional cerebral blood flow was measured by a laser Doppler flowmeter to check the ischemic condition. Infarction area was assessed by 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological scores were determined by a modified version of the method described by Longa et al. Emboli were accumulated at the temporal or parietal region of the middle cerebral artery. Additionally, we found that this model showed decreased cerebral blood flow and increased infarction area and neurological scores. Treatment with tissue plasminogen activator (t-PA) reduced infarction area and the neurological scores in a dose-dependent manner; moreover, the decreased cerebral blood flow recovered. SMTP-7 also reduced these values. The therapeutic time window of SMTP-7 was longer than that of t-PA. These results indicate that this model may be useful for understanding the pathophysiological mechanisms of cerebral infarction and evaluating the effects of therapeutic agents. Additionally, SMTP-7 is a promising approach to extend the therapeutic time window. Therefore, this novel compound may represent a novel approach for the treatment of cerebral infarction.

Long-term functional and neurological outcome after simultaneous treatment with tissue-plasminogen activator and hyperbaric oxygen in early phase of embolic stroke in rats.

The combination of hyperbaric oxygen therapy (HBO) and recombinant tissue-plasminogen activator (tPA) is of interest in the treatment of acute ischemic stroke with a view to combine positive effects of both strategies. We investigated neurological and functional outcome after early treatment with HBO additional to tPA in ischemic stroke. Focal cerebral ischemia was induced using an embolic stroke model in 87 male Wistar rats. Animals were randomized to therapy with tPA+HBO, tPA alone, or control. Menzies score, Beam walk, and the Corner test were assessed for a period of 4 weeks following ischemia. Within the first 24 h neurological deficits improved in all groups but most pronounced in animals treated with tPA+HBO. Thereafter, a deterioration of neurological deficits occurred in the tPA+HBO group with significant differences at day 7, 8, 18, and 24 (P<0.05). Surprisingly, Beam walk and Corner test results did not differ significantly between all groups. This first report of early simultaneous treatment with tPA and HBO in experimental embolic stroke with 4-week follow-up confirms previous studies reporting positive effects of HBO shortly after the ischemia. Following the acute phase, combined tPA and HBO resulted in deterioration of neurological deficits without affecting functional recovery. Future studies should focus on interactions of tPA and HBO on molecular level leading to delayed damage to brain tissue at risk.

Atorvastatin extends the therapeutic window for tPA to 6 h after the onset of embolic stroke in rats.

We investigated the neuroprotective effect of atorvastatin in combination with delayed thrombolytic therapy in a rat model of embolic stroke. Rats subjected to embolic middle cerebral artery (MCA) occlusion were treated with atorvastatin at 4 h, followed by tissue plasminogen activator (tPA) at 6 or 8 h after stroke. The combination of atorvastatin at 4 h and tPA at 6 h significantly decreased the size of the embolus at the origin of the MCA, improved microvascular patency, and reduced infarct volume, but did not increase the incidence of hemorrhagic transformation compared with vehicle-treated control animals. However, monotherapy with tPA at 6 h increased the incidence of hemorrhagic transformation and failed to reduce infarct volume compared with the control group. In addition, adjuvant treatment with atorvastatin at 4 h and with tPA at 6 h reduced tPA-induced upregulation of protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, and concomitantly reduced cerebral microvascular platelet, neutrophil, and fibrin deposition compared with rats treated with tPA alone at 6 h. In conclusion, a combination of atorvastatin and tPA extended the therapeutic window for stroke to 6 h without increasing the incidence of hemorrhagic transformation. Atorvastatin blocked delayed tPA-potentiated adverse cerebral vascular events, which likely contributes to the neuroprotective effect of the combination therapy.

Hyperbaric oxygenation in fluid microembolism.

Because clinicians require objectively demonstrable neurological deficits to confirm a diagnosis, the recognition of embolic events in the nervous system is generally restricted to the effects of ischemic necrosis produced by arterial occlusion. However, magnetic resonance imaging (MRI) has shown that lesser degrees of damage associated with small emboli are common, especially in the mid brain, and are usually clinically silent. They are frequently associated with atheromatous embolism in the elderly, but microembolic debris, such as fat, is common in the systemic venous return of healthy people and generally trapped in the microcirculation of the lung being removed by phagocytosis. However, pulmonary filtration may fail and microemboli may also pass through an atrial septal defect in so-called 'paradoxical' embolism. Studies of bubbles formed on decompression in diving have demonstrated the importance of pulmonary filtration in the protection of the nervous system and that filtration is size dependant, as small bubbles may escape entrapment. Fluid and even small solid emboli, arresting in or passing through the cerebral circulation, do not cause infarction, but disturb the blood-brain barrier inducing what has been termed the 'perivenous syndrome'. The nutrition of areas of the white matter of both the cerebral medulla and the spinal cord depends on long draining veins which have been shown to have surrounding capillary free zones. Because of the high oxygen extraction in the microcirculation of the gray matter of the central nervous system, the venous blood has low oxygen content. When this is reduced further by embolic events, tissue oxygenation may fall to critically low levels, leading to blood-brain barrier dysfunction, inflammation, demyelination and eventually, axonal damage. These are the hallmarks of the early lesions of multiple sclerosis where MR spectroscopy has also shown the presence of lactic acid. Significant elevation of the venous oxygen tension requires oxygen to be provided under hyperbaric conditions. Arterial tension is typically increased ten-fold breathing oxygen at 2 atmospheres absolute (ATA), but this results in only a 1.5-fold increase in the cerebral venous oxygen tension. The treatment of decompression sickness, and both animal and clinical studies, have confirmed the value of oxygen provided under hyperbaric conditions in the restoration and preservation of neurological function in the 'perivenous' syndrome.

Embolismo gaseoso cerebral por accidente de buceo / Cerebral gas embolism as a result of diving accident

La patología relacionada con los accidentes de buceo es quizás poco conocida por su baja prevalencia. Se clasifica en no disbárica o disbárica, en función de su relación con cambios de presión. Presentamos el caso de un buceador que, después de realizar una inmersión de 30 minutos a 22 metros de profundidad, presentó bradipsiquia y afasia transitoria. En la tomografía axial computarizada craneal se objetivó un infarto silviano izquierdo. Se realizó tratamiento en cámara hiperbárica con buena evolución clínica. En relación con el caso, revisamos las distintas formas de presentación de los accidentes disbáricos, así como la utilidad de la cámara hiperbárica en el tratamiento

Clinical alterations related to diving accidents are little known perhaps because of its low prevalence. They can be classified as dysbarism-related and non-dysbarism-related according to its relation with pressure changes. We present the case of a diver that showed bradypsychia and transitory aphasia after carrying out an immersion of 30 minutes in duration and 22 meters deep. A left sylvian cerebral infarct was demostrated in cranial computerized axial tomography. Treatment was carried out in a hyperbaric chamber with good clinical evolution. We review with regard to this case the different forms of clinical presentation of dysbarism-related accidents, as well as the usefulness of the hyperbaric chamber in their treatment

Catastrophic reaction in acute stroke: a reflex behavior in aphasic patients.

Twelve patients with a catastrophic reaction (CR) (an outburst of frustration, depression, and anger when confronted with a task) were identified in a prospective cohort population (n = 326) with first-ever stroke admitted within 48 hours from onset. The authors' findings suggest that CR is a rare though not exceptional phenomenon in acute stroke and is associated with nonfluent aphasias and left opercular lesions. CR, poststroke depression, and emotionalism are distinct but related disorders.

Bilateral thalamic infarction. Clinical, etiological and MRI correlates.

To determine clinical, behavioral, topographic and etiological patterns in patients with simultaneous bilateral thalamic infarction in varied thalamic artery territories, we studied 16 patients who were admitted to our stroke unit over a 7-year period. Patients with bithalamic infarction represented 0.6% of our registry which included 2,750 ischaemic stroke patients. On computed tomography and magnetic resonance imaging with gadolinium enhancement, there were 4 topographic patterns of infarction: 1) bilateral infarcts in the territory of paramedian artery (8 patients [50%]); 2) bilateral infarcts in the territory of thalamogeniculate arteries (3 patients [19%]); 3) bilateral infarcts involving territory of paramedian and thalamogeniculate arteries (3 patients [19%]); 4) bilateral infarcts involving territory of polar and thalamogeniculate arteries (2 patients [13%]). A specific clinical picture was found in up to 50% of the patients with bithalamic infarction. This included patients with bilateral paramedian infarction having disorder of consciousness, memory dysfunctions, various types of vertical gaze palsy and psychic changes. Bilateral sensory loss predicted accurately bilateral infarction in the territory of thalamogeniculate arteries. The main cause of bilateral thalamic infarction was small artery-disease, followed by cardioembolism. Cognitive functions in patients with bilateral paramedian infarction did not change significantly during the follow-up, in contrast to those with infarcts in varied arterial territories. Acute bilateral infarction involving both thalamus is uncommon, although they are often associated with specific neurologic-neuropsychological patterns, allowing diagnosis before radiological examination.