Angioarchitecture and prognosis of pediatric intracranial pial arteriovenous fistula.

OBJECTIVE: Pial arteriovenous fistulas (PAVFs) are rare and mostly observed in children. However, the overall angioarchitecture, clinical features, treatments and long-term prognosis for pediatric patients remain unclear. METHODS: Clinical data of consecutive 42 pediatric PAVFs were documented and analysed. According to the differences of age distribution and clinical features, they were split into a younger group (≤3 years old; 20 cases) and an older group (3-14 years old; 22 cases). RESULTS: Their mean age was 4.9±3.9 years, and the mean preoperative modified Rankin Scale (mRS) score was 1.64±1.57. Fourteen patients (33.3%) were asymptomatic, followed by epilepsy (21.4%), intracranial haemorrhage (16.7%), hydrocephalus (9.5%), developmental delay (7.1%), intermittent headache (7.1%) and congestive heart failure (4.8%). Annual bleeding rate and rebleeding rate before treatment reached 3.86% and 3.17%. Poor venous drainage including sinus dynamic obstruction (21 cases, 50.0%) and sinus occlusion (17 cases, 40.48%) were found with high frequency among these patients. Finally, 33 cases were cured (78.57%), and 4 cases faced surgery-related complications (9.52%). During 24-140 months' follow-up, the mean mRS score reduced to 0.57±0.40. However, only 22 cases (52.38%) recovered to absolutely normal, and poor venous drainage was the risk factor for patients' incomplete recovery (p=0.028, Exp(B)=14.692, 95% CI 1.346 to 160.392). Compared with the older group, younger group showed more chronic symptoms, more secondary pathological changes, more times treatment and worse prognosis (p=0.013, 0.002, 0.000 and 0.032, respectively). CONCLUSIONS: Pediatric PAVF has different angioarchitectures, clinical features and prognoses in different age groups. Poor venous drainage is an important factor leading to poor prognosis, and it accounts for incomplete recovery in nearly half of patients.

A clinically relevant model of focal embolic cerebral ischemia by thrombus and thrombolysis in rhesus monkeys.

Over decades of research into the treatment of stroke, nearly all attempts to translate experimental treatments from discovery in cells and rodents to use in humans have failed. The prevailing belief is that it might be necessary to pretest pharmacological neuroprotection in higher-order brains, especially those of nonhuman primates (NHPs). Over the past few years, chemical thrombolysis and mechanical thrombectomy have been established as the standard of care for ischemic stroke in patients. The spotlight is now shifting towards emphasizing both focal ischemia and subsequent reperfusion in developing a clinically relevant stroke model in NHPs. This protocol describes an embolic model of middle cerebral artery occlusion in adult rhesus monkeys. An autologous clot is combined with a microcatheter or microwire through endovascular procedures, and reperfusion is achieved through local intra-artery thrombolysis with tissue plasminogen activator. These NHP models formed relatively stable infarct sizes, delivered predictable reperfusion and survival outcomes, and recapitulated key characteristics of patients with ischemic stroke as observed on MRI images and behavioral assays. Importantly, treated animals could survive 30 d after the surgery for post-stroke neurologic deficit analyses. Thus far, this model has been used in several translational studies. Here we describe in detail the teamwork necessary for developing stroke models of NHPs, including the preoperation preparations, endovascular surgery, postoperation management and histopathological analysis. The model can be established by the following procedures over a 45-d period, including preparation steps (14 d), endovascular operation (1 d) and evaluation steps (30 d).

Treatment of spontaneous spinal epidural hematoma in children: analysis of 25 cases.

INTRODUCTION: Spontaneous spinal epidural hematoma (SSEH) is a rare neurosurgical emergency, presenting as sudden onset of back pain and weakness of lower extremities. Many patients have no definite cause. Some cases of SSEH caused by vascular malformation have been reported. The treatment strategy remains controversial. This study aimed to analyze the causes of SSEH and proposed a treatment strategy according to clinical outcomes of patients at a single institution. METHODS: A total of 25 cases of SSEH under 18 years of age treated between March 2004 and July 2021 were retrospectively analyzed. RESULTS: The mean age of the first SSEH onset was 7.1 years. The most common location was cervicothorax. Nine patients suffered from multiple episodes. Twenty-three patients underwent spinal digital subtraction angiography (DSA), of which seven (30.4%) patients had positive findings: three cases had epidural artery venous fistula (AVF), two cases had epidural artery venous malformation (AVM), and two cases had abnormal concentration of contrast agent. Seventeen patients received surgery. Eleven patients (44%) were diagnosed as vascular malformation by either DSA or pathology. The follow-up rate was 80%, with 20 patients (80%) achieving satisfactory clinical outcome. Risk factors for poor clinical outcome included multiple episodes (p = 0.028) and higher Aminoff-Logue score (p = 0.005). CONCLUSION: Spinal epidural vascular malformation is a significant cause of SSEH. Spinal DSA is necessary. Surgery should be recommended for patients with multiple episodes, positive findings on DSA, or severe neurological deficits. Conservation therapy can be considered for other patients, but long-time follow-up is necessary.

Intranasal salvinorin A improves neurological outcome in rhesus monkey ischemic stroke model using autologous blood clot.

Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm3 vs. 7.2 ± 1.0 cm3; P = 0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P = 0.002), and diffusion limitation in the lesion (-28.2 ± 11.0% vs. -51.5 ± 7.1%; P = 0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group (P = 0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.

Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status.

Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes - complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.

Inflammatory cytokines are involved in dihydrocapsaicin (DHC) and regional cooling infusion (RCI)-induced neuroprotection in ischemic rat.

OBJECTIVE: The combination of pharmacological hypothermia - dihydrocapsaicin (DHC) and intra-arterial regional cooling infusions (RCI) was found to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection in acute ischemic stroke. The aim of this study was to explore whether the combination could induce a long-term neuroprotective effects, as well as the underlying mechanism. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h using intraluminal hollow filament. The ischemic rats were randomized to receive pharmacological hypothermia by intraperitoneal (i.p.) injection of DHC, physical hypothermia by RCI of 6 ml cold saline (4 °C), the combination, and no treatment. Over a 21-day period, brain damage was determined by infarct volume with MRI, and neurological deficit with grid-walking and beam balance tests. Blood brain barrier (BBB) was assessed by Evans-Blue (EB) contents. Inflammatory cytokines were determined in peri-infarct area by antibody array and ELISA. RESULTS: The combination of DHC and RCI reduced (p < 0.05) infarct volume and neurologic deficit after stroke. BBB leakage and pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) were significantly decreased (p < 0.05) because of the combination, while protective cytokines (IL-4 and IL-10) were increased (p < 0.05) in the peri-infarct area. CONCLUSIONS: The combination approach enhanced the efficacy of hypothermia-induced neuroprotection following ischemic stroke. Our findings provide a hint to translate the combination method from bench to bedside.

Pediatric perimedullary arteriovenous fistula: clinical features and endovascular treatments.

OBJECTIVE: Pediatric spinal perimedullary arteriovenous fistula (PMAVF) is rare but may cause permanent disability. We aim to summarize the clinical features of pediatric PMAVFs and our clinical experience in their treatment and to evaluate the effect of endovascular treatment in a large cohort. METHODS: From 2008 to 2017, 51 PMAVFs in pediatric patients (<14 years' old) treated with endovascular techniques were retrospectively reviewed, including 24 type IVb (47.1%) and 27 type IVc (52.9%) lesions. Clinical features, radiological findings, treatment, and outcomes were evaluated. RESULTS: Thirty-eight boys and thirteen girls were included, and the mean age at presentation was 5.6±4.1 years. Acute neurological deterioration was identified in 33 patients, and 21 of those patients (63.6%) suffered from bleeding. The annual bleeding rate before treatment was 2.55%. After transarterial embolization with coils and glue, 46 PMAVFs (90.2%) were completely occluded, and five (9.8%) were obliterated by supplementary microsurgery. During a follow-up period of 6 to 119 months (mean 58.4±16.7 months), the patients' clinical states were improved in 42 cases (82.4%), stationary in nine cases (17.6%), and aggravated in none. Type IVc patients had a longer preoperative period, more chronic symptoms, a lower cure rate by embolization, and less improvement of symptoms than type IVb patients had (P<0.05). CONCLUSIONS: Pediatric PMAVF is a special subgroup of intradural arteriovenous shunt that should be treated early. Endovascular embolization is safe and effective in the treatment of pediatric PMAVFs.

Clipping of a Pediatric Pial Arteriovenous Fistula Located at Basilar Artery Tip Using a Hybrid Trapping-Evacuation Technique.

BACKGROUND: Intracranial pial arteriovenous fistulas (PAVFs) are rare cerebrovascular lesions with high mortality rates. We report a rare case of pediatric PAVF at the basilar artery tip and its treatment with surgical clipping aided by a trapping-evacuation technique in a hybrid operating room. CASE DESCRIPTION: An 18-month-old boy was admitted with hypoevolutism and 4-month history of weakness in the left extremities. Magnetic resonance imaging showed a giant aneurysm-like malformation in the area of midbrain and pons. Angiography showed a high-flow PAVF fed by the basilar artery and bilateral P1 segments of the posterior cerebral artery, with deep draining veins into the transverse sinus and straight sinus. Given the intrinsic characteristics of the lesion, such as deep location, giant fistula and varix, and multiple feeding arteries, clipping of PAVF was performed in a hybrid operating room aided by a trapping-evacuation technique to clearly identify and block the shunting point. CONCLUSIONS: The successful obliteration of the lesion is reported. In addition, a brief review of literature comparing endovascular embolization, surgical disconnection, and hybrid technique for treatment of PAVF is included.

A congenital external carotid artery-external jugular vein arteriovenous fistula was successfully treated by coil embolization (case report and literature review).

OBJECT: Congenital arteriovenous fistula involving the external carotid system is rare. METHODS: This paper reports a case of congenital external carotid artery-external jugular vein arteriovenous fistula admitted to Xuanwu Hospital, and reviews the literature. RESULTS: The patient was a boy, 9 years old, with a history of pulsatile mass and thrill in the right neck since his birth. External carotid artery-external jugular vein fistula was confirmed by the digital subtraction angio-graphy. And coil embolization was done later. Postoperative immediate angiography confirmed the complete occlusion of the fistula, and partial branch of the external carotid artery can be seen. The abnormal clinical manifestation disappeared after the procedure without any complications. CONCLUSION: This case and relevant literatures remind us that congenital external carotid artery-external jugular vein arteriovenous fistula has its unique features, and it can be treated by coil embolization safely and effectively.

A trapping-evacuation technique for giant carotid-ophthalmic segment aneurysm clipping in a hybrid operating theater.

It is essential to collapse giant carotid-ophthalmic (OA) segment aneurysms for successful microsurgical clipping. We present a trapping-evacuation technique utilising hybrid operating theater capabilities to soften OA aneurysms. The patients were prepared for both microsurgical and endovascular procedures. After the majority of the aneurysm was exposed, a balloon was placed at the orifice of the aneurysm to fully block the blood flow. When the balloon was inflated, blood was evacuated from the aneurysm sac to eliminate the space occupying effect. Subsequently, the aneurysm neck was clearly exposed which greatly facilitated clip placement. A control angiogram was obtained prior to closing the wound to ensure complete aneurysm obliteration. After the establishment of a hybrid operating theater in our hospital, two aneurysms were successfully clipped using this technique. Although postoperative complications occurred in both patients, none of the events were related to the endovascular procedure or the trapping-evacuation technique. As a well-organized procedure designed for use in a hybrid operating theater, the current trapping-evacuation technique is an option for the surgical clipping of giant OA aneurysms.

Serine/Threonine Protein Phosphatase-5 Accelerates Cell Growth and Migration in Human Glioma.

Glioma is the most common type of primary central nervous system tumor. Ser/Thr protein phosphatase 5 (PP5) has been shown to regulate multiple signaling cascades that suppress growth and facilitate apoptosis in several human cancer cells. However, the role of PP5 in human gliomas remains unclear. Herein, the relationship between PP5 expression and glioma cell growth was investigated, and the therapeutic value of PP5 in glioma was further evaluated. We employed a short hairpin RNA targeting PPP5C gene to knock down PP5 expression in human glioma cell lines U251 and U373. Depletion of PPP5C via RNAi remarkably inhibited glioma cell proliferation and colony formation, and arrested cell cycle in the G0/G1 phase. Moreover, knockdown of PP5 markedly suppressed glioma cell migration, as determined by Transwell assay. Our findings suggest that PPP5C could be essential for glioma cell growth and serve as a promising therapeutic target in human gliomas.

[Feasibility and efficiency of embolization of spinal dural arteriovenous fistula].

OBJECTIVE: To evaluate the feasibility and efficiency of embolization of spinal dural arteriovenous fistula (SDAVF). METHODS: From December 2010 to May 2012, there were 104 cases of SDAVF were treated, and 26 cases were selected to be treated with embolization. The inclusion criteria was as follows: (1) No anterior or posterior spinal artery originated from the fistula segment; (2) The segmental artery can be catheterized with guiding or micro catheter; (3) High flow in fistula; (4) Patient's situation was not suitable for surgery or general anesthesia. Among 26 cases, there were 22 male and 4 female patients, the average age was 55.9 years (ranged from 34 to 81 years). The locations of SDAVF were 10 cases in thoracic, 9 in lumbar and 7 in sacral segment. The main symptoms were progressive numbness and weakness in both lower extremities, most cases accompanied with difficulties in urination and defecation. The average history was 17.1 months (from 1 to 156 months). ONYX-18 liquid embolic agent or Glubran-2 surgical glue were used as embolic material. The patients not cured with embolization were treated with surgery in the following 1 - 2 weeks. Follow-up evaluation was done with MRI after 3 months and DSA after 6 months, besides physical examination. RESULTS: Fifteen from 26 cases achieved immediate angiographic cure results: 14 in 20 cases which embolized with ONYX-18; only 1 in 6 cases with Glubran-2. Three in 10 cases of thoracic SDAVF and 12 in 16 cases of lumbar/sacral SDAVF were cured with embolization. Partially embolized cases were treated with surgical obliteration of drainage veins within 2 weeks. Cured patients experienced immediate improvement after embolization and kept getting better in the follow-up. All the patients had MRI follow-up after 3 months and DSA follow-up after 6 months. In 6 month's follow-up, MRI showed the edema and flow void signal in the spinal cord disappeared. DSA showed no fistula recurrence or remnant. There was no deterioration case in all of the embolized cases. CONCLUSIONS: Particular SDAVF is suitable for embolization with ONYX-18. Most lesions located in lumbar and sacral segment are good indications for embolization.

Traumatic spinal perimedullary arteriovenous fistula due to knife stabbing and subsequent kyphosis: case report.

Perimedullary arteriovenous fistula (AVF) is a relatively rare spinal vascular malformation. Although it has traditionally been considered to be a congenital lesion, some cases identified in adults have suggested that the lesion may be acquired. The etiology and exact mechanism of these lesions are unknown. The authors present a case of a perimedullary AVF caused by a direct stabbing injury of the spinal cord and induced by subsequent kyphosis, and they discuss the pathogenesis and treatment strategy.

Traumatic intracranial aneurysms due to blunt brain injury-a single center experience.

BACKGROUND: Traumatic intracranial aneurysms (TICAs) have previously been described in literature. However, the evidence of TICAs secondary to blunt brain injury have not been elucidated well, with most of the conclusions coming from isolated case reports. We have attempted to examine the epidemiology, classification, clinical presentation, therapeutic modalities, and outcomes of TICAs with our series of patients at the neurosurgery department of Xuanwu Hospital, China. METHODS: We reviewed our aneurysm database from January 1, 2005 to December 31, 2011. In particular, patients with TICAs secondary to blunt brain injury were reviewed. Variables assessed included age, sex, causes of blunt brain injury, skull fracture, location, classification, clinical presentation, time elapsed to arrive at diagnoses, treatment, and eventual outcome. Based on our assessment, we arrived at a modified classification scheme to categorize these aneurysms. RESULTS: We reviewed 2335 patients with cerebral aneurysm from January 1, 2005 to December 31, 2011. Of these, 15 patients (0.64 %) with traumatic aneurysms secondary to blunt brain injury were identified.Motor vehicle accidents (MVA) were observed to be the most common cause of injury (10 patients, 66.7 %), followed by TICAs sustained after falling down (5 patients, 33.3 %). The most common symptom at presentation was epistaxis (6 patients, 40 %), followed by ophthalmic problems (6 patients, 40 %), with both presentations seen in 1 patient. The most common diagnostic modality used was DSA in 12 patients (80 %) followed by CTA in 2 patients (13.3 %). Infraclinoid TICAs were seen in 9 patients (60 %), whereas supraclinoid TICAs were seen in 5 patients (33.3 %), with perifalx TICAs seen in 1 patient. Endovascular intervention therapies were performed in 11 patients (73.3 %), bypass surgery and trapping in 2 (13.3 %), transnasal endoscopic approach in combination with balloon assisted in 2 patients. At discharge, 2 patients had poor clinical outcomes (13.3 %), 5 had fair (33.3 %),and 8 resulted with good outcomes (53.3 %). CONCLUSIONS: TICAs arising secondary to blunt brain injury account for 0.64 % of all cerebral aneurysms. Infraclinoid, supraclinoid ICA and perifalx TICAs are the most common aneurysms arising from blunt brain injury. Our study further shows that traumatic patients presenting with recurrent epistaxis, oculomotor nerve palsy, and delayed intracranial hemorrhage should receive cerebroangiography as soon as possible. An early diagnosis and proper treatment could prove to be helpful in terms of improving final clinical outcome.

[Treatment of cutaneous vertebral medullary angiomatosis].

OBJECTIVE: Cutaneous vertebral medullary angiomatosis, also known as Cobb's syndrome, is a part of spinal arteriovenous metameric syndromes (SAMs), is derived from the vascular malformation triad of skin, bone, and spinal cord involvement. It is poorly managed with current treatment modalities. We reviewed the treatment of Cobb's syndrome series and summarized the experiences. METHODS: A total of 61 cases of Cobb's syndrome with spinal cord dysfunction were treated at our department from February 2003 to December 2007. The treatment followed the same strategy: First step-investigating the pathogenic mechanisms by symptom onset, MRI, angiography and the response to initial treatment. Second step-treating the problematic parts of the lesions with embolization alone, surgery alone or combination of both. Forty-eight cases were embolized, 3 cases treated with surgery and 10 cases treated with a combination of both. Nidus involving pathogenic mechanism for spinal cord were eliminated, completely and nearly disappeared in 36 cases and partially in 25 cases. All patients were followed up regularly. RESULTS: Among these 61 cases, the pathogenic mechanisms were identified as hemorrhage, mass effect, ischemia and venous hypertensive myelopathy. Two or more mechanisms could coexist in the same patient. More than 1-year's spinal cord function follow-up showed: excellent in 9 cases, good in 26, fair in 23 and worse in 3. CONCLUSION: Not all lesions of Cobb's syndrome can be or should be cured anatomically. Pathogenic mechanism should be analyzed carefully and the treatment should focus on the special cord-affecting targets. Long-term improvement or stabilization may be achieved.

The clinical features and treatment of pediatric intracranial aneurysm.

PURPOSE: Intracranial aneurysms are relatively rare in the pediatric population. The objective of this study was to highlight the clinical and radiological features and the therapeutic outcome and clarify the choice of therapeutic strategies for pediatric intracranial aneurysms. MATERIALS AND METHODS: Twenty-four consecutive children (age

[Correlative study of carotid transient ischemic attacks and intracranial or extracranial angiostenosis].

OBJECTIVE: To investigate the relationship between the clinical features of carotid transient ischemic attacks (TIA) and the intracranial or extracranial angiostenosis. METHODS: Location and degree of stenosis of involved arteries were examined by the digital subtraction angiography in 52 patients with carotid TIA. RESULTS: Intracranial or extracranial vascular lesions of different degrees were revealed in 45 patients (86.5%), and 29 out of 45 (64.4%) had more than one site. Severe stenosis and occlusion occurred more frequently in TIA patients with short duration (less than 1 hour) and multiple attacks (more than twice). CONCLUSION: Most patients with TIA of carotid systems have stenosis in intracranial or extracranial arteries. TIA with short duration and multiple attacks always accompany with severe stenosis or occlusion in intracranial or extracranial arteries. Digital subtraction angiography helps to identify the vascular etiology of TIA and provides the instruction of therapeutic regimen.

[Different methods of intracranial-extracranial bypass surgery for the treatment of intracranial aneurysms].

OBJECTIVE: To investigate the effects and methods of intracranial-extracranial (IC-EC) bypass surgery in the treatment of intracranial aneurysms. METHODS: The clinical material of 9 cases, who performed IC-EC bypass surgery before occlusion of the parental arteries of intracranial aneurysms, was studied retrospectively, especially how to evaluate the co-lateral circulation of the parental arteries and how to select the different methods of IC-EC bypass surgery. RESULTS: The co-lateral circulation in 9 cases was not enough to meet the need of the cerebral blood flow after occlusion of the parental arteries of the aneurysms. Revascularization by different methods of IC-EC bypass surgery and then occlusion of the parental arteries, ischemia in the brain area feeding by occluded parental arteries of the aneurysms did not occurred. CONCLUSION: When the co-lateral circulation of the parental arteries of intracranial aneurysm is not enough, the revascularization by different methods of IC-EC bypass surgery is needed before occlusion of these arteries.