Pathological Safety Assessment in Preclinical Neurothrombectomy Studies.

The design, production, and preclinical testing of neurothrombectomy devices is in a burgeoning phase as the demand escalates for safe and reliable treatment options following neurovascular stroke. Currently, there is a paucity of published data describing the development of iatrogenic vascular lesions occurring secondary to neurothrombectomy procedures. In an effort to test new devices, demonstrate device safety, satisfy regulatory requirements, and develop an understanding of the potential for associated vascular pathology, investigators are establishing appropriate methodology in suitable animal models. Significant challenges exist in identifying a single animal species that can be consistently utilized in all phases of device development. These aforementioned challenges are underscored by the intricacies of neurovascular pathology, thrombovascular interactions, and vascular responses to injury.

Magnetic resonance vessel wall imaging in cerebrovascular diseases

Cerebrovascular diseases manifest as abnormalities of and disruption to the intracranial vasculature and its capacity to carry blood to the brain. However, the pathogenesis of many cerebrovascular diseases begins in the vessel wall. Traditional luminal and perfusion imaging techniques do not provide adequate information regarding the differentiation, onset, or progression of disease. Intracranial high-resolution MR vessel wall imaging (VWI) has emerged as an invaluable technique for understanding and evaluating cerebrovascular diseases. The location and pattern of contrast enhancement in intracranial VWI provides new insight into the inflammatory etiology of cerebrovascular diseases and has potential to permit earlier diagnosis and treatment. In this report, technical considerations of VWI are discussed and current applications of VWI in vascular malformations, blunt cerebrovascular injury/dissection, and steno-occlusive cerebrovascular vasculopathies are reviewed.

Cervicocranial artery dissection and scuba diving: Is there a link or is it serendipity?

INTRODUCTION: Numerous reports have documented cervicocranial artery dissection (CCAD) associated with scuba diving. The question remains as to whether there are risk factors unique to scuba diving related to the occurrence of CCAD. OBJECTIVES: This article aims to perform an examination of the reported cases to demonstrate any commonality among the injured divers and association with known risk factors for CCAD. METHODS: A PubMed search was performed utilizing the key words: carotid artery dissection, dissection, arterial dissection, cranial artery dissection, scuba, diving, scuba diving. Articles including reports, reviews, trials, case series, and letters were considered. Each report was critically dissected for information specific to the dive itself and the diver and analyzed for similarities and consistency with known risks. RESULTS: Twelve (12) reports of CCAD associated with scuba diving were identified. Activities involved with scuba diving appear to be consistent with CCAD risk factors. It is unclear if hyperbaric stress and physiological changes during a dive present specific risk. Trauma - e.g., environmental protection and activities associated with diving - was identified as a common risk factor in all cases. Ten (10) cases involved arteries at anatomic sites commonly associated with dissections. Seven divers documented to have dive profiles suspicious of decompression sickness were identified. CONCLUSIONS: There appears to be a correlation with minor traumas that occur with diving and CCAD. The inconsistency of the dive-related specific information reported makes it impossible for investigation of hyperbaric stress-related risk factors for CCAD to be analyzed.

Trauma of the extracranial cerebral arteries due to injuries of the cervical spine.

INTRODUCTION: Cervical spine injuries are immanently accompanied by trauma to cerebral neck arteries. METHOD: A prospective two-cohort study, from oct. 2013 to oct. 2015. Overall 76 Patients (39W/37M) of median age 77 years, with either fractures or discoligamentary injuries have been examined with duplex-sonography and or CT-angiography. From October 2013 to October 2017 we examined 155 Patients (49% female and 51% male), with the average age of 39 years, SD 19 and age median of 34 years, with cervical-spine-distortion, using the same diagnostic modalities. We used the statistics-program Bias 11.01. RESULTS: The overall incidence of traumatic dissection of the internal carotid artery was 2.5%, in 50% of cases (1.2%) with neurological symptomato-logy. For the vertebral artery seems the incidence of 10.5%, with 25% of symptomatic patients (2.6%) comparably high. We have identified the osteophytes and dislocation as the significant risk factors. The canalis vertebralis and the skull-base are regions mostly prone to vascular injury. In the group of cervical spine distorsions we found no vascular trauma at all. The osteophytes were here identified as the main risk factor for collateral damage. CONCLUSION: One should look for vascular injuries in case of cervical relevant spine trauma. Moreover,  a rather relevant osteoligamentous injury should be assumed, when cervical vascular trauma was diagnosed. Key words: cervical spine trauma vessel-dissection duplex-sonography CT-angiography.

Clinical Significance of Wall Changes After Recanalization Therapy in Acute Stroke: High-Resolution Vessel Wall Imaging.

BACKGROUND AND PURPOSE: Owing to the excellent recanalization rate of endovascular treatment, new outcome predictors are required for patients with acute stroke, who have sufficient recanalization. In this study, the effects of recanalization therapy on occluded arteries in patients with acute stroke were investigated using high-resolution vessel wall imaging. METHODS: Twenty-nine patients with stroke were included in the study. High-resolution vessel wall imaging was performed on patients with acute stroke and adequate postrecanalization results. We characterized the postrecanalization arterial wall changes as concentric enhancements and plaques and examined the associations of the postrecanalization changes with procedural factors and neurological outcomes. RESULTS: The most frequent high-resolution vessel wall imaging finding was concentric enhancement, which was associated with thrombectomy procedural factors such as the number of procedures and the type of device. Concentric enhancements were associated with hemorrhagic transformation, whereas plaque was not associated with procedural details. CONCLUSIONS: The use of high-resolution vessel wall imaging after successful recanalization can provide information about postrecanalization arterial wall changes and clinical outcomes.

Alzheimer's disease and CADASIL are heritable, adult-onset dementias that both involve damaged small blood vessels.

This essay explores an alternative pathway to Alzheimer's dementia that focuses on damage to small blood vessels rather than late-stage toxic amyloid deposits as the primary pathogenic mechanism that leads to irreversible dementia. While the end-stage pathology of AD is well known, the pathogenic processes that lead to disease are often assumed to be due to toxic amyloid peptides that act on neurons, leading to neuronal dysfunction and eventually neuronal cell death. Speculations as to what initiates the pathogenic cascade have included toxic abeta peptide aggregates, oxidative damage, and inflammation, but none explain why neurons die. Recent high-resolution NMR studies of living patients show that lesions in white matter regions of the brain precede the appearance of amyloid deposits and are correlated with damaged small blood vessels. To appreciate the pathogenic potential of damaged small blood vessels in the brain, it is useful to consider the clinical course and the pathogenesis of CADASIL, a heritable arteriopathy that leads to damaged small blood vessels and irreversible dementia. CADASIL is strikingly similar to early onset AD in that it is caused by germ line mutations in NOTCH 3 that generate toxic protein aggregates similar to those attributed to mutant forms of the amyloid precursor protein and presenilin genes. Since NOTCH 3 mutants clearly damage small blood vessels of white matter regions of the brain that lead to dementia, we speculate that both forms of dementia may have a similar pathogenesis, which is to cause ischemic damage by blocking blood flow or by impeding the removal of toxic protein aggregates by retrograde vascular clearance mechanisms.

Avoidance of postoperative epistaxis and anosmia in endonasal endoscopic skull base surgery: a technical note.

BACKGROUND: Most endoscopic transsphenoidal approaches jeopardize the sphenopalatine artery and septal olfactory strip (SOS), increasing the risk of postoperative anosmia and epistaxis while precluding the ability to raise pedicled nasoseptal flaps (NSF). We describe a bilateral "rescue flap" technique that preserves the mucosa containing the nasal-septal vascular pedicles and the SOS. This approach can reduce the risk of postoperative complications, including epistaxis and anosmia. METHODS: A retrospective analysis was conducted of all patients who underwent endoscopic transsphenoidal surgery with preservation of both sphenopalatine vascular pedicles and SOS. In a recent subset of patients, olfactory assessment was performed. RESULTS: Of 174 consecutive operations performed in 161 patients, bilateral preservation of the sphenopalatine vascular pedicle and SOS was achieved in 139 (80 %) operations, including 31 (22 %) with prior transsphenoidal surgery. Of the remaining 35 operations, 18 had a planned formal NSF and 17 had prior surgery or extensive lesions precluding use of this technique. Of pituitary adenomas, RCCs or sellar arachnoid cysts, 118 (94 %) underwent this approach, including 91 % of patients who had prior surgery. Preoperative olfaction function was maintained in 97 % of patients that were tested. None of the patients had postoperative arterial epistaxis. CONCLUSION: Preservation of bilateral sphenopalatine vascular pedicles and the SOS is feasible in over 90 % of patients undergoing endonasal endoscopic surgery for pituitary adenomas and RCCs. This approach, while not hindering exposure or limiting instrument maneuverability, preserves the nasoseptal vasculature for future NSF use if needed and appears to minimize the risks of postoperative arterial epistaxis and anosmia.

Imaging of blunt vascular neck injuries: a clinical perspective.

OBJECTIVE: We will review the common injuries and anatomic distributions of blunt cerebrovascular injuries (BCVIs) of the neck, explain the grading criteria, and discuss the corresponding management. Artifacts associated with BCVI on CT will also be examined. CONCLUSION: Identifying common injury patterns and anatomic distributions associated with BCVI can help decide the grade and management earlier and reduce the risk for potential complications. Recognizing the common artifacts associated with BCVI helps the reader successfully recognize a true BCVI.

Apoptosis, paraptosis, necrosis, and cell regeneration in posttraumatic cerebral arteries.

This study is to understand the nature and functional significance of the activated cell death programs and rehabilitation signs during late vascular changes after brain injury. We used light and transmission electron microscopy to describe changes of cells within the vascular endothelium and tunica media of the cortical arteries four weeks after craniocerebral traumatism. Within tunica media of the posttraumatic damaged artery, apoptotic and paraptotic phenotypes were identified as well as some early ultrastructural signs of smooth muscle cells regeneration, these cell highlighting a remarkable degree of plasticity. Surprisingly, some endothelial cells showed an extensive rough endoplasmic reticulum development, whereas other endothelial cells showed typical necrosis. In conclusion, two groups of suicidal cells apoptotic and paraptotic cells were encountered in the same lesional vascular wall after neurotrauma, showing also signs of cell regeneration. The pathophysiologic significance of the coexisting double cell death programs and cell regeneration seems to be in relation with late cell survival, after arterial damage when some cells disappear and other cells try to survive undergoing reversible injury.

Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence.

BACKGROUND: Acute ischemic strokes are associated with poor outcomes and high health care burden. Evidence exists evaluating the use of neurothrombectomy devices in patients receiving currently recommended treatments that may have limited efficacy. PURPOSE: To describe the state of the evidence supporting use of neurothrombectomy devices in the treatment of acute ischemic stroke. DATA SOURCES: MEDLINE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Web of Science were searched, without language restrictions, from their inception through May 2010. The MEDLINE and Cochrane Central Register of Controlled Trials searches were updated through November 2010. STUDY SELECTION: Two independent investigators screened citations for human studies of any design or case series or case reports of patients with an acute ischemic stroke that evaluated a neurothrombectomy device and reported at least 1 clinical effectiveness outcome or harm. DATA EXTRACTION: Using standardized protocols, 2 independent investigators extracted information about study characteristics and outcomes, and a third reviewer resolved disagreement. DATA SYNTHESIS: 87 articles met eligibility criteria, including 18 prospective single-group studies, 7 noncomparative retrospective studies, and 62 case series or case reports. Two U.S. Food and Drug Administration (FDA)-cleared devices, the MERCI Retriever (Concentric Medical, Mountain View, California) (40%) and the Penumbra System (Penumbra, Alameda, California) (9%), represented a large portion of the available data. All prospective and retrospective studies provided data on successful recanalization with widely varying rates (43% to 78% with the MERCI Retriever and 83% to 100% with the Penumbra System). Rates of harms, including symptomatic (16 studies; 0% to 10% with the MERCI Retriever and 0% to 11% with the Penumbra System) or asymptomatic (13 studies; 28% to 43% and 1% to 30%, respectively) intracranial hemorrhage and vessel perforation or dissection (11 studies; 0% to 7% and 0% to 5%, respectively), also varied by device. Predictors of harm included older age, history of stroke, and higher baseline stroke severity scores, whereas successful recanalization was the sole predictor of good outcomes. LIMITATIONS: Most available data are from single-group, noncomparative studies. In addition, the patient population most likely to benefit from these devices is undetermined. CONCLUSION: Currently available neurothrombectomy devices offer intriguing treatment options in patients with acute ischemic stroke. Future trials should use a randomized design, with adequate power to show equivalency or noninferiority between competing strategies or devices, and strive to identify populations that are most likely to benefit from use of neurothrombectomy devices. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Effect of erythrocytes on brain water content and haem oxygenase-1 expression in rats with traumatic intracerebral haemorrhage.

BACKGROUND: Studies have demonstrated that brain oedema formation following spontaneous intracerebral haemorrhage is associated with substances derived from blood clots or blood components. However, these studies did not completely reveal the role of blood components in brain oedema formation following traumatic intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in brain oedema development by studying the effect of erythrocytes on brain water content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH. METHODS: A total of 120 Sprague-Dawley rats were randomly divided into four experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs (PRBC). Following TBI, which was established by applying a free-falling device, WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. RESULTS: In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the greatest. However, BWC in the LRBC group at 1 day was markedly higher than that at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC group was the highest at 1 day, and the highest at 3 days in the WB and PRBC groups; there was no significant difference at 5 days. Positive expression of HO-1 in the WB, PRBC and LRBC groups coincided with changes in BWC. CONCLUSIONS: Our results indicate that erythrocytes play an important role in delayed brain oedema formation (3 days post-injury) following TICH, but have no significant influence on brain oedema at early stages (1 day post-injury), and that the mechanisms of delayed brain oedema involve RBC breakdown products.

[Traumatic arteriovenous pial fistula masquerading as a carotid-cavernous fistula: an uncommon disorder with an unusual presentation]. / Fístula arteriovenosa pial traumática que simula una fístula carotidocavernosa: una enfermedad infrecuente con una presentación excepcional.

Traumatic intracranial pial arteriovenous fistulae are infrequent lesions. Their cardinal signs have been related to mass effect and hemorrhage, but their clinical manifestations due to venous retrograde flow into ophthalmic veins has never been described. This phenomenon is usually seen in dural arteriovenous fistula draining to the cavernous sinus or carotid-cavernous sinus fistula.A traumatic intracranial pial arteriovenous fistula arising from the supraclinoid internal carotid artery in a young patient was revealed by aggressive behavior and ophthalmologic manifestations. The endovascular management included the use of coils, stent, and ethylene-vinyl alcohol with transient balloon occlusion of the parent vessel.

PICA injury secondary to anterior odontoid screw fixation: Case report of an exceptional complication.

BACKGROUND: Odontoid fracture is a common injury in the upper cervical spine that can sometimes be managed by anterior odontoid screw fixation. CASE DESCRIPTION: We report the first case of iatrogenic postero-inferior cerebellar artery (PICA) injury while performing anterior odontoid screw fixation for a type II odontoid fracture in a 22-year-old man. Fisher grade 4 subarachnoid hemorrhage secondary to iatrogenic pseudoaneurysm formation was managed by the endovascular neuroradiologist. Odontoid fracture was then managed posteriorly using Harm's technique. Postoperative 12-month follow-up revealed good clinical and radiological results. CT scan showed fusion. Complete exclusion of the pseudo aneurysm with a mild stroke in the inferior left cerebellar hemisphere were noted on the MRI. There were no cerebellar ataxia or swallowing disorders. CONCLUSION: To the best of our knowledge, this is the first case report of iatrogenic PICA injury in anterior odontoid screw fixation. The patient was well managed in our institution within a multidisciplinary team. We recommend that surgical management of odontoid fractures should be performed in expert centres.

The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo.

NO plays critical roles in vascular function. We show that modulation of the eNOS serine 1179 (S1179) phosphorylation site affects vascular reactivity and determines stroke size in vivo. Transgenic mice expressing only a phosphomimetic (S1179D) form of eNOS show greater vascular reactivity, develop less severe strokes, and have improved cerebral blood flow in a middle cerebral artery occlusion model than mice expressing an unphosphorylatable (S1179A) form. These results provide a molecular mechanism by which multiple diverse cardiovascular risks, such as diabetes and obesity, may be centrally integrated by eNOS phosphorylation in vivo to influence blood flow and cardiovascular disease. They also demonstrate the in vivo relevance of posttranslational modification of eNOS in vascular function.

Review of long-term mortality and vascular morbidity amongst young adults with cerebral infarction.

The incidence of cerebral infarction amongst patients <45 years ranges from 3.4 to 11.3 per 100,000. Aetiology of cerebral infarction is more heterogeneous amongst young patients than amongst older patients including frequent dissection of neck vessels. Because of longer expected survival, prognosis is of special importance amongst younger patients. Average annual long-term mortality rate after the first year of cerebral infarction ranges from 0.6% to 1.8% and is about 10 times higher than amongst matched controls. Long-term mortality is associated with cardiac embolism and atherosclerosis, whilst dissection of neck vessels is associated with low long-term mortality. Average annual long-term recurrence rate of cerebral infarction ranges from 0.3% to 1.7% after the first year. Recurrence of cerebral infarction and other vascular events is highly associated with traditional risk factors including smoking, diabetes mellitus and symptomatic atherosclerosis. Dissection of neck vessel is associated with low long-term mortality rate and low recurrence rate of cerebral infarction. Tailoring secondary preventive treatment according to aetiology and risk factors suggests better prognosis.

Expanded transnasal approaches to the skull base in the Middle East: Where do we stand?

BACKGROUND: Endoscopic transnasal surgery has gained rapid global acceptance over the last two decades. The growing literature and understanding of anterior skull base endoscopic anatomy, in addition to new dedicated endoscopic instruments and tools, have helped to expand the use of the transnasal route in skull base surgery. OBJECTIVE: Report our early experience in expanded endoscopic transnasal surgery (EETS) and approach to skull base neoplasms. DESIGN: Descriptive, retrospective case series. SETTING: Major tertiary care center. PATIENTS AND METHODS: A retrospective case review was conducted at King Saud University Medical City between December 2014 and August 2019. Cases with skull base neoplasms that underwent EETS were included. EETS was defined as endoscopic surgical exposure that extended beyond the sellar margins (prechiasmatic sulcus superiorly, clival recess inferiorly, cavernous carotid lines laterally). Routine transsphenoidal pituitary neoplasms, neoplasms of sinonasal origin and meningoencephaloceles were excluded. MAIN OUTCOME MEASURES: Preoperative clinical assessment, imaging results, surgical approach, and hospital course were all retrieved from the patient electronic charts. Clinical follow-up, perioperative complications, and gross residual tumor rates were documented and reviewed. SAMPLE SIZE AND CHARACTERISTICS: 45 cases of EETS, 13 males and 32 females with mean age of 39.0 (17.7) years (range 2-70 years). RESULTS: The series comprised a wide range of pathologies, including giant pituitary adenoma (8 cases), meningioma (23 cases), craniopharyngioma (4 cases), chordoma (4 cases), optic pathway glioma (2 cases), epidermoid neoplasms (2 cases), astrocytoma (1 case), and teratoma (1 case). For the entire series, gross total resection was achieved in 25/45 operations (55.5%). Postoperative cerebrospinal fluid leak was the most common complication observed in 9 patients (20%) which were all managed endoscopically. Major vascular complications occurred in 2 patients (4.4%) and are described. Other complications are outlined as well. No mortality was observed. CONCLUSIONS: EETS to the skull base can be done with results comparable to traditional approaches. More work is needed to expand our experience, improve outcomes, and educate the public and medical community in our region about the usefulness of this approach. LIMITATIONS: Sample size and study design. CONFLICT OF INTEREST: None.

Ruptured Posterior Inferior Cerebellar Artery Dural Fistula After Vestibular Schwannoma Resection.

A 50-year-old man with a history of left-sided retrosigmoid craniotomy for vestibular schwannoma (VS) resection 19 years prior presented with severe headache and left cerebellopontine angle subarachnoid hemorrhage (SAH). Digital subtraction angiography demonstrated a dissected, nonfunctional left posterior inferior cerebellar artery with direct fistulization at the left transverse sinus (Video 1). The lesion was treated with endovascular Onyx embolization. The patient recovered without neurologic deficit. Five additional cases of new dural arteriovenous fistula arising after VS resection have been described; we report the first such case presenting with SAH, suggesting that postoperative magnetic resonance angiography may be of value in long-term VS follow-up imaging protocols.

Cotton-Assisted Surgical Clipping of Very Small Aneurysms: A Two-Center Study.

OBJECTIVE: Very small intracranial aneurysms (VSIAs) are challenging to treat because aneurysm tearing and clip slippage can occur during neurosurgical clipping. In this study, we introduce and share our experience with cotton-assisted clipping of VSIAs. METHODS: We retrospectively analyzed the data of 20 patients with 24 VSIAs treated with cotton-assisted clipping between February 2008 and December 2014 in the Neurosurgery Departments of the First Affiliated Hospital, Soochow University and Taizhou People's Hospital. During surgery, 2 aneurysm necks were torn. To treat the tears, we wrapped rectangular cotton pads around the parental arteries at the site of rupture. The remaining 22 aneurysms were clipped after being wrapped in cotton pads. RESULTS: The 2 aneurysm ruptures were successfully repaired with cotton-assisted clipping. In the remaining 22 aneurysms, no cases of aneurysm clip slippage or aneurysm rupture occurred. Patients were followed up on average for 59.0 months (range, 30-113 months). Of the 20 patients, the 16 patients with preoperative Hunt-Hess grades of 1-3 recovered well after the surgery (Glasgow Outcome Scale [GOS] score, 5). Of the 4 patients with Hunt-Hess grades of 4-5, 3 had a good recovery (GOS scores, 4-5), and 1 patient died of heart disease 6 months after being discharged from the hospital; this patient had a GOS score of 4 at the time of discharge. CONCLUSIONS: Cotton-assisted clipping could prevent aneurysm clip slipping and aneurysm rupture and facilitate the repair of aneurysm neck tears. This technique is a useful alternative therapy for VSIAs.

[Case report of traumatic hemorrhage from the anterior choroidal artery].

Traumatic hemorrhage from the anterior choroidal artery is very rare. A 74-year-old male was admitted to our hospital immediately after a traffic accident. CT on admission showed right intracerebral hematomas in the posterior limb of the internal capsule and the upper part of the right cerebral peduncle. Neurological examination revealed that the patient had left hemiparesis and transient mute, pseudobulbar sign and peduncular hallucination. The absence of hypertensive asymptomatic microbleeds in other basal ganglia supported the verdict of traumatic injury of the anterior choroidal artery. The tear mechanism of the anterior choroidal artery might have been caused by an impact to the parietal region directed toward the tentorium.