Interactions between neutrophil extracellular traps and activated platelets enhance procoagulant activity in acute stroke patients with ICA occlusion.

BACKGROUND: The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) in stroke patients caused by thromboembolic occlusion of the internal carotid artery (ICA) remains unclear. Our objectives were to evaluate the critical role of NETs in the induction of hypercoagulability in stroke and to identify the functional significance of NETs during atherothrombosis. METHODS: The levels of NETs, activated platelets (PLTs), and PLT-derived microparticles (PMPs) were detected in the plasma of 55 stroke patients and 35 healthy controls. NET formation and thrombi were analysed using immunofluorescence. Exposed phosphatidylserine (PS) was evaluated with flow cytometry and confocal microscopy. PCA was analysed using purified coagulation complex, thrombin, and fibrin formation assays. FINDINGS: The plasma levels of NETs, activated PLTs, and PMP markers in the carotid lesion site (CLS) were significantly higher than those in the aortic blood. NETs were decorated with PS in thrombi and the CLS plasma of ICA occlusion patients. Notably, the complementary roles of CLS plasma and thrombin-activated PLTs were required for NET formation and subsequent PS exposure. PS-bearing NETs provided functional platforms for PMPs and coagulation factor deposition and thus increased thrombin and fibrin formation. DNase I and lactadherin markedly inhibited these effects. In addition, NETs were cytotoxic to endothelial cells, converting these cells to a procoagulant phenotype. Sivelestat, anti-MMP9 antibody, and activated protein C (APC) blocked this cytotoxicity by 25%, 39%, or 52%, respectively. INTERPRETATION: NETs played a pivotal role in the hypercoagulability of stroke patients. Strategies that prevent NET formation may offer a potential therapeutic strategy for thromboembolism interventions. FUNDING: This study was supported by grants from the National Natural Science Foundation of China (61575058, 81873433 and 81670128) and Graduate Innovation Fund of Harbin Medical University (YJSKYCX2018-58HYD).

Internal carotid artery aneurysm mimicking normal-tension glaucoma.

Differentiating glaucomatous from nonglaucomatous optic disc cupping remains challenging. We present a case of a 48-year-old woman with an internal carotid aneurysm of approximately 3.5 mm × 6.5 mm that mimicked normal-tension glaucoma. The patient had a 2-year history of low vision acuity in her left eye and frontal oppressive headache. Owing to the carotid aneurysm, she developed an asymmetric vertical cup-to-disc ratio above 0.2, and marked inferotemporal neuronal rim loss and pallor of the residual rim were noted in the left disc. She also developed a visual field defect with an arcuate scotoma in the left eye. The patient was referred to a neurosurgeon and underwent endovascular aneurysm occlusion. This case highlights the diagnostic importance of recognizing that many neurological defects remain underdiagnosed.

Internal carotid artery aneurysm mimicking normal-tension glaucoma / Aneurisma de carótida interna simulando glaucoma de pressão normal

ABSTRACT Differentiating glaucomatous from nonglaucomatous optic disc cupping remains challenging. We present a case of a 48-year-old woman with an internal carotid aneurysm of approximately 3.5 mm × 6.5 mm that mimicked normal-tension glaucoma. The patient had a 2-year history of low vision acuity in her left eye and frontal oppressive headache. Owing to the carotid aneurysm, she developed an asymmetric vertical cup-to-disc ratio above 0.2, and marked inferotemporal neuronal rim loss and pallor of the residual rim were noted in the left disc. She also developed a visual field defect with an arcuate scotoma in the left eye. The patient was referred to a neurosurgeon and underwent endovascular aneurysm occlusion. This case highlights the diagnostic importance of recognizing that many neurological defects remain underdiagnosed.

RESUMO diferenciação de escavações glaucomatosas e não glaucomatosas ainda permanece um desafio ainda nos dias de hoje. Nos descrevemos um caso de aneurisma de carótida interna medindo 3.5mm x 6.5mm que simulava um glaucoma de pressão normal. O caso é sobre uma paciente feminino de 48 anos com história de 2 anos de baixa acuidade visual no olho esquerdo e cefaléia frontal. Devido ao aneurisma de carótida a paciente desenvolveu uma assimetria de escavação vertical maior que 0.2 no olho esquerdo em relação ao direito com defeito localizado da camada de fibras nervosas temporal inferior. Ela também apresentava um defeito arqueado temporal superior a esquerda, cruzando a linha média vertical consistente. Após o diagnostico confirmado pela ressonância magnética funcional, a paciente foi enviada para o neurocirurgião para realização de uma oclusão endovascular do aneurisma. Esse caso nos alerta da importância de se lembrar que não apenas o glaucoma gera escavações suspeitas no disco óptico e que ainda muitos defeitos por causas neurológicas são subdiagnosticados.

Hypothalamic, thalamic and hippocampal lesions in the mouse MCAO model: Potential involvement of deep cerebral arteries?

Intraluminal monofilament occlusion of the middle cerebral artery (MCAO) in mice is the most used rodent model to study the pathophysiology of stroke. However, this model often shows brain damage in regions not supplied by the MCA such as the hypothalamus, hippocampus and thalamus. Several studies have suggested some explanations on these localized infarcts. We aim to provide an alternative explanation which could allow each experimenter to better grasp the MCAO model. We propose that the MCA occlusion by the monofilament also occludes deep and small cerebral arteries arising directly from the internal carotid artery, proximally to the origin of MCA. Then, drawbacks and pitfalls of the MCAO model must be appreciated and the almost systematic risk of inducing lesions in some unwanted territories for neuroanatomical reasons, i.e. vascular connections between deep arteries and hypothalamic, thalamic and hippocampal areas in rodents has to be integrated.

Isolated Horner Syndrome From an Elongated Styloid Process (Eagle Syndrome).

Eagle syndrome occurs when an elongated styloid process causes otolaryngological or neurological symptoms or signs. We report a patient who had an isolated asymptomatic Horner syndrome that resulted from a pinned internal carotid artery being dynamically injured by an elongated styloid process during chiropractic neck manipulation. There was no evidence of arterial dissection.

Progressão atípica de perda visual em paciente com glaucoma primário de ângulo aberto / Atypical progression of visual loss in a patient with primary open-angle glaucoma

A dolicoectasia da artéria carótida interna (ACI) é uma condição rara que pode ser acompanhada de manifestações neuro-oftalmológicas, como perda da acuidade e alteração do campo visual decorrente da compressão do nervo óptico (NO). O objetivo é relatar um caso de paciente do sexo masculino, 67 anos, portador de glaucoma primário de ângulo aberto (GPAA) com evolução atípica, assimetria de escavação, palidez da rima do NO à esquerda, devido à neuropatia óptica compressiva à esquerda, por segmento dolicoectásico da ACI. O diagnóstico foi baseado na história clínica, aspecto do NO e exames de neuroimagem.

Dolichoectasia of the internal carotid artery (ICA) is a rare condition that may be associated with neuro-ophthalmic manifestations, such as loss of visual acuity and visual field resulting from compression of the optic nerve (ON). The aim is to report a 67-year-old male patient with primary open-angle glaucoma (POAG) with atypical evolution, asymmetry of cupping and increased pallor of the rim of the left ON, due to compressive optic neuropathy by the dolichoectatic segment. The diagnosis was based on clinical history, appearance of the ON and neuroimaging.

Carotid artery stenting: a therapeutic alternative in subtotal internal carotid artery occlusions.

Carotid artery stenting (CAS) is emerging as a less invasive modality for treating atherosclerotic occlusive disease of the internal carotid artery (ICA). Randomized trials like the SAPPHIRE trial have demonstrated that CAS is not inferior to carotid endarterectomy (CEA) in the treatment of carotid artery stenosis, and maybe even superior in high-risk symptomatic patients. However, patients with subtotal ICA occlusions with thrombus are excluded from randomized CAS trials and CAS registries. To our knowledge, carotid angioplasty with stenting has not been attempted in these cases. We present three cases of symptomatic subtotal ICA occlusions successfully treated with CAS without any periprocedural complications. With careful patient selection and technical expertise, endovascular management could be considered as a treatment option in subtotal carotid occlusions.

MR contrast probes that trace gene transcripts for cerebral ischemia in live animals.

The aim of this research was to validate transcription magnetic resonance (MR) imaging (MRI) for gene transcript targeting in acute neurological disorders in live subjects. We delivered three MR probe variants with superparamagnetic iron oxide nanoparticles (SPION, a T2 susceptibility agent) linked to a phosphorothioate-modified oligodeoxynucleotide (sODN) complementary to c-fos mRNA (SPION-cfos) or beta-actin mRNA (SPION-beta-actin) and to sODN with random sequence (SPION-Ran). Each probe (1 microg Fe in 2 microl) was delivered via intracerebroventricular infusion to the left cerebral ventricle of male C57Black6 mice. We demonstrated SPION retention, measured as decreased T2* signal or increased R2* value (R2* = 1/T2*). Animals that received the SPION-beta-actin probe exhibited the highest R2* values, followed (in descending order) by SPION-cfos and SPION-Ran. SPION-cfos retention was localized in brain regions where SPION-cfos was present and where hybrids of SPION-cfos and its target c-fos mRNA were detected by in situ reverse transcription PCR. In animals that experienced cerebral ischemia, SPION-cfos retention was significantly increased in locations where c-fos mRNA increased in response to the ischemic insult; these elevations were not observed for SPION-beta-actin and SPION-Ran. This study should enable MR detection of mRNA alteration in disease models of the central nervous system.

Bilateral occipital infarcts associated with carotid atherosclerosis and a persistent hypoglossal artery.

The persistent hypoglossal artery (PHA) is the second most common persistent embryological carotid-basilar connection and usually represents an incidental finding in cerebral arteriograms. The hypoglossal artery connects the primordial carotid artery with the longitudinal neural arteries, which later form the basilar artery. The PHA leaves the internal carotid artery as an extracranial branch, enters the skull through the anterior condyloid foramen, the hypoglossal canal and joins the caudal portion of the basilar artery. We report magnetic resonance and digital subtraction angiography findings in the first case of bilateral occipital infarctions associated with PHA and carotid atherosclerosis. The probable mechanism underlying bilateral occipital infarcts was embolism from the carotid territory to the posterior cerebral arteries. PHA may present a challenge in diagnosis and management of patients with carotid atherosclerosis and vertebrobasilar ischemia.

Selective alteration of native, but not second language articulation in a patient with foreign accent syndrome.

The present study deals with a right-handed female polyglot suffering from a Foreign Accent Syndrome (FAS) which affects her native language (L1), but not her other languages learnt since the age of 12. She had a small infarct in the left corona radiata as the result of a carotid occlusion. Her L1 was Spanish, but she also had a good command of French, English and Catalan (L2). Aphasia tests did not reveal any other significant alteration in any language. Analyses of pre-morbid and post-morbid voice recordings revealed that FAS affected Spanish dramatically, but no important changes were observed for French. Results were interpreted as showing that different brain areas control articulation of L1 and L2 learnt after a critical period.

Extracranial internal carotid artery aneurysm presenting as symptomatic hypoglossal and glossopharyngeal nerve paralysis.

Aneurysms of the extracranial portion of the internal carotid artery are rare, particularly in young patients. They usually develop following trauma, or secondary to infection involving the parapharyngeal space that extends to the vessel wall. This is a case of an internal carotid artery aneurysm presenting acutely following chiropractic neck manipulation with hypoglossal and glossopharyngeal nerve palsy. The imaging findings and subsequent operative management are described.

fMRI of the auditory cortex in patients with unilateral carotid artery steno-occlusive disease.

PURPOSE: To examine whether an internal carotid artery (ICA) steno-occlusive disease leads to a reduced blood oxygenation level dependent (BOLD)-signal change due to a decreased vasodilatory reserve capacity. MATERIALS AND METHODS: Patients suffering from unilateral ICA stenosis or occlusion were examined using functional magnetic resonance imaging (fMRI) of the auditory cortex with a bilateral stimulation applying a pulsed 1000 Hz sine-tone. RESULTS: Compared to control subjects, who showed symmetric bilateral BOLD-responses within the auditory cortex, the ICA patients revealed either a normal bilateral cortical activation pattern or a reduced cortical activation on the steno-occluded side. This latter decrease of BOLD-signal change might indicate a depressed vasomotor reserve capacity. The observed coincidence between this asymmetric reduction in BOLD-signal and ischemic borderzone lesions on the affected side in this subgroup of patients strongly supports this assumption. CONCLUSION: This study shows that fMRI of the auditory cortex appears to have clinical merit in the workup of cerebrovascular conditions.

Horner's syndrome and dissection of the internal carotid artery after chiropractic manipulation of the neck.

PURPOSE: To report a case of Horner's syndrome and dissection of the internal carotid artery after chiropractic manipulation of the neck. METHODS: Case report. A 44-year-old woman with no prior ocular or vascular history presented with severe right-sided head and neck pain, ptosis, and miosis following chiropractic treatment for a strained right shoulder muscle. RESULTS: Magnetic resonance angiography of the neck and brain revealed a dissection of the right internal carotid artery as well as a suggestion of subtle dissection in the right vertebral artery. No significant brain abnormalities were noted on magnetic resonance imaging. Pharmacological testing was consistent with preganglionic oculosympathetic damage. CONCLUSION: Acute, painful Horner's syndrome as a manifestation of vascular dissection may be associated with chiropractic manipulation of the neck.

[Surgery of the internal carotid: locoregional or general anesthesia?]. / Chirurgie de la carotide interne: anesthésie locorégionale ou générale?

AIM OF THE STUDY: The aim of this retrospective study was to assess the advantages of regional anesthesia over general anesthesia in carotid artery surgery. PATIENTS AND METHOD: From January 1989 to December 1998, 670 patients with severe internal carotid artery stenosis were operated in the same center and were classified into two groups according to the type of anesthesia: group I, general anesthesia (n = 312) and group II, regional anesthesia (n = 358). Characteristics of the two groups were almost similar except for a higher rate of unstable heart disease in group I and bypass grafts in group II. RESULTS: A shunt was used in 16.3% of cases in group I and in 8.4% in group II. Complications resulting from the use of a shunt and intraoperative complications observed with regional anesthesia were reported. There was a conversion from regional to general anesthesia in 6 patients. Median duration of clamping was longer in group II (30 min vs 25 min). Cardiac complication rates were similar in the two groups, particularly cardiac mortality (0.6%). There were more pulmonary and miscellaneous complications in group I. Neurological complications were more frequent in group I, particularly fatal strokes (1% versus 0%). Neurological mortality and morbidity cumulative rates were 3.1% and 1.5%, respectively, not significantly different. CONCLUSION: These results, in agreement with those of the literature, confirm that carotid artery endarterectomy is associated with a low rate of neurological mortality and morbidity. Although regional anesthesia was associated with a lower rate of complications, we are not allowed to conclude to its superiority, as the present study was retrospective and the difference was not statistically significant.

A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor.

BACKGROUND AND PURPOSE: The aim of this study was to develop a new model of stroke based on endothelial damage and thrombotic occlusion in a perforating artery, leading to small cerebral infarcts and neurological deficits in rats. Moreover, the neuroprotective efficacy of fasudil, a rho-kinase inhibitor, was investigated in this model. METHODS: Fifty-six male Sprague-Dawley rats were used in the present study. Rats were anesthetized with sodium pentobarbital, and 100 microg of sodium laurate was injected into the left internal carotid artery on days 1 and 3. The thrombus induction and consequent of ischemic brain damage were examined by histopathological analyses and neurological deficit scoring in a posture reflex test. To investigate the neuroprotective effects of fasudil, 1 or 10 mg/kg was administered intraperitoneally 5 minutes after the first injection of sodium laurate and once daily thereafter on the following 2 days. RESULTS: One hour after the injection of sodium laurate, microscopic examination of phosphotungstic acid hematoxylin-stained sections (n=5) revealed that microthrombi containing fibrin strands obstructed the perforating arteries in the ipsilateral hemisphere. Under a transmission electron microscope (n=6), endothelial cells appeared exfoliated and the vascular lumen was obstructed by a thrombus composed of degranulated platelets, fibrin, leukocytes, and erythrocytes. No evidence of endothelial cell damage or thrombus could be found in the ipsilateral side of the pial artery (middle cerebral artery). Twenty-four hours after the second injection of sodium laurate (day 4), 13 of 15 rats (86.6%) showed mild to severe neurological deficits. Multiple small cerebral infarcts were observed in the hippocampus, cortex, and thalamus. Treatment with fasudil (1 and 10 mg/kg, n=15 each) resulted in a significant improvement in neurological deficits. Fasudil also significantly reduced the area of cerebral infarction. CONCLUSIONS: We present a new model of stroke in rats, in which the perforating arteries are selectively occluded by microthrombi. This model is useful to investigate the pathophysiology and treatment of small cerebral infarction, which is caused by perforating arterial occlusive diseases such as lacunar infarcts. Fasudil may be beneficial in the treatment of acute ischemic stroke.

[Endosonography of the pharynx]. / Endosonographie des Pharynx.

BACKGROUND: Endosonography is a diagnostic tool for the examination of tumors of the oral cavity. The pharynx is usually not assessable for conventional endosonography due to problems with the placement of the probe in deeper areas of the pharynx. PATIENTS: A fingertop ultrasonography probe was combined with a stick allowing the user to locate the probe in deeper areas of the pharynx. The stick had two flexible joints and a device for attaching the probe in the front. We evaluated 48 patients with tumors of the posterior wall of the pharynx (n = 6), lateral wall of the pharynx (n = 7), tonsil (n = 17), sinus piriformis (n = 13), and nasopharynx (n = 5) during preoperative tumor endoscopy under general anesthesia. Thirty-two patients suspected of having a tonsillar abscess were examined under local anesthesia. RESULTS: The evaluation of the tumor dissemination and the determination of the relationship between the tumor and the internal carotid artery was excellent for tumors of the posterior and lateral wall of the pharynx. The investigation of tumors of the sinus piriformis and the nasopharynx was difficult and tumor growth could not be determined normally with endosonography. In four cases, retropharyngeal lymph nodes could be detected. The sensitivity for the diagnosis of tonsillar abscesses was 84%. CONCLUSION: Endosonography of the deeper areas of the pharynx seems to be a useful instrument for investigating growth of tumors at the lateral and posterior wall of the pharynx. Endosonographic results might be helpful for deciding between endoscopic and external approaches. Endosonography is not sufficiently sensitive for diagnosing tonsillar abscesses, but might be helpful in clinically difficult cases.

Carotid endarterectomy in patients with contralateral carotid occlusion: review of a 10-year experience.

A total of 116 carotid endarterectomies were performed in patients with a totally occluded opposite internal carotid artery over a 10-year period from 1983 until 1992. The average age of patients was 66.4 years; 75% were men and 25% were women. The average degree of stenosis on the operated side was 76.7%. Twenty-one patients (18.1%) had had a documented previous stroke referrable to the side of the occlusion; 22 had a neurologic deficit attributable to the occluded vessel at the time of preoperative evaluation. Indications for surgery included transient ischemic attacks in 35 (30.2%), ipsilateral stroke in 10 (8.6%), amaurosis fugax in 11 (9.5%), and high-grade asymptomatic stenosis in 60 (51.7%). Forty-eight percent of the procedures were performed using local anesthesia, with intraluminal shunts inserted in all except one patient. The combined 30-day mortality and stroke morbidity in this population was 4.3%, which is comparable with a combined stroke and death rate of 4.0% among 956 patients without contralateral carotid occlusion undergoing endarterectomy during this period. This experience suggests that endarterectomy can be performed safely in the patient with internal carotid occlusion and is an important mechanism for the prevention of stroke.