Operative versus non-operative management of posterior fossa epidural hematoma: A systematic review and meta-analysis.

BACKGROUND: Posterior fossa epidural hematoma (PFEDH) is rare, occurring in less than 3% of head injuries. It can be managed either operatively or non-operatively. Management guidelines date from 2006, without recent updates providing class III evidence. METHOD: We searched PubMed and other databases for English language observational studies up to 2021 that compared the two treatment approaches for PFEDH and. RESULTS: Twenty-four of the 350 references, for involving 874 patients, met the study criteria. Conservative management showed higher GOS 5 scores and lower mortality. GCS 13-15 patients were more prevalent in the conservative group. Surgical cases often involved ventriculomegaly/compression, hydrocephalus or contusion. CONCLUSION: The study shed light on surgical versus conservative PFEDH management, although evidence is sparse. Generally, conservative methods showed better initial outcomes, and should be preferred. However, respect of individual patient traits and Brain Trauma Foundation guidelines is crucial: conservative management may not suit all cases. To enhance the evidence base, RCTs are important for optimal PFEDH management. Bridging this gap can substantially improve patient outcomes and clinical decision-making, emphasizing the need to consider both the available evidence and patient-specific factors for effective guidance.

Long term clinical and radiological outcomes following surgical treatment of symptomatic cranial arachnoid cyst: A population based consecutive cohort study.

OBJECTIVE: Symptomatic intracranial arachnoid cysts are treated mainly through surgical resection, endoscopic fenestration, or by implanting cystoperitoneal (CP) shunt. However, the use of a specific technique remains controversial. The purpose of this study is to discuss these surgical modalities in symptomatic patients with intracranial arachnoid cysts (ACs) and investigate which has better outcomes and less complications by comparing variable preoperative and postoperative parameters. METHODS: An analysis of thirty-nine symptomatic patients who underwent intracranial arachnoid cyst surgery in the department of neurosurgery between 2009 and 2023 was performed. Patients were retrospectively compared based on age group, gender, anatomical location, laterality, type of intervention, clinical and volumetric changes, postoperative complications and outcome. RESULTS: Of the 39 patients, 20 patients (51.28 %) received CP shunt. Eleven patients (28.2 %) underwent endoscopic fenestration, and 8 patients (20.5 %) had surgical resection. The age at the time of first operation ranged from 1 month to 59.9 years (mean age: 16.8 years), and the pediatric patients were 25 (64.1 %). The most common initial symptom was headache which was observed in 19 patients (48.7 %), followed by seizure in 12 patients (30.8 %), vomiting in 11 patients (28.2 %), visual dysfunction in 8 patients (20.5 %), drowsiness in 8 patients (20.5 %), visual symptoms in 8 patients (20.5 %), cognitive impairment in 4 patients (10.3 %), focal neurological deficits in 3 patients (7.7 %), and cranial nerve involvement in 1 patient (2.6 %). 24 patients (61.5 %) showed improvement while in 15 patients (38.5 %) the symptoms persisted or worsened. Postoperatively, patients were followed up for an average of one year. The highest improvement rate was noted in endoscopic fenestration with 9 improved patients (81.8 %), followed by surgical resection with 5 symptom-free patients (62.5 %). The worst outcomes were seen in cystoperitoneal shunt with only half of the patients were relieved (50 %). Complications developed in 2 patients (25 %) who underwent surgical resection, 5 patients (45.5 %) who had endoscopic fenestration, and 13 patients (65 %) who had cystoperitoneal shunting. CONCLUSION: Endoscopic fenestration has the highest improvement rate, the lowest serious complications along with being the least invasive technique. These features make it the optimal modality in treatment of ACs. Surgical resection or cystoperitoneal shunt can be considered as secondary techniques when patients report unchanged or worsening symptoms.

Risk of meningitis after posterior fossa decompression with duraplasty using different graft types in patients with Chiari malformation type I and syringomyelia: a systematic review and meta-analysis.

Several complications have been reported after the use of grafts for duraplasty following posterior fossa decompression for the treatment of Chiari malformation type I. This study aims to investigate the rate of meningitis after posterior fossa decompression using different types of grafts in patients with Chiari malformation type I and associated syringomyelia. The search was conducted using multiple databases, including PubMed, Scopus, Web of Science, and Embase. Data on the rate of meningitis, syrinx change, and rate of reoperation were extracted and investigated. Quality of evidence was assessed using the Newcastle-Ottawa scale. Nineteen studies were included in the final meta-analysis, encompassing 1404 patients and investigating autografts, synthetic grafts, allografts, and xenografts (bovine collagen, bovine pericardium, and pig pericardium). Autografts were associated with the lowest rate of meningitis (1%) compared to allografts, synthetic grafts, and xenografts (2%, 5%, and 8% respectively). Autografts were also associated with the lowest rate of reoperation followed by xenografts, allografts, and synthetic grafts (4%, 5%, 9%, and 10% respectively). On the other hand, allografts were associated with the highest rate of syrinx improvement (83%) in comparison to autografts and synthetic grafts (77%, and 79% respectively). Autografts were associated with the lowest meningitis, reoperation, and syrinx improvement rates. Furthermore, synthetic grafts were associated with the highest reoperation and xenografts with the highest rate of meningitis, whereas allografts were associated with the best syrinx improvement rate and second-best meningitis rate. Future studies comparing autografts and allografts are warranted to determine which carries the best clinical outcome.

Management and Outcome of a Neurologically Intact Infant with Pierre Robin Sequence and Dandy-Walker Variant Diagnosed with Large Hemispheric Brain Abscess ­ Case Report

Pierre Robin sequence (PRS) is a condition consisting of three essential components: micrognathia or retrognathia, cleft palate, and glossoptosis. It can be part of multiple congenital anomalies. We present the case and outcome of a 3-month-old clinically stable patient who has PRS with Dandy-Walker variant ­ which is a rare presentation in the literature ­ with a large right hemispheric brain abscess, treated with multiple minimally-invasive surgical drainage procedures with adjuvant antibiotics.

Secondary spinal cord changes and spinal deformity following traumatic spinal cord injury.

Secondary spinal cord changes can follow spinal cord injuries (SCIs). This retrospective study was to uncover the chronic secondary changes that affect the spinal cord following severe injuries and to evaluate the influence of residual spinal deformity in the development of posttraumatic spinal cord changes. Fifty-eight patients (39 male, 19 female) with complete traumatic SCI and recent Magnetic resonance imaging (MRI) follow-up were reviewed retrospectively. A minimum of 2 years duration between trauma and MRI study was required (mean 2.9 years [2.1-4.7]). Two groups of patients were formed: with spinal deformity (and or spinal canal compromise) and without spinal deformity (and or spinal canal compromise). MRI of the injured spine demonstrated four major types of spinal cord changes; these are spinal cord atrophy, myelomalacia, syrinx, and focal cyst formation. The correlation of these changes to the presence of spinal deformity and or spinal canal compromise was also studied. Twenty-three patients (40%) of the studied population had more than 30° kyphosis and or 50% compromise of the spinal canal. Chronic spinal cord changes occurred in 25 patients (43%), 17 of these changes occurred in patients with spinal deformity and the remaining 8 occurred in patients without spinal deformity or canal compromise (p ≤ .05). The prevalence of spinal cord atrophy and focal cysts was significantly higher in patients with residual deformity and or spinal canal compromise (p ≤ .05). The authors recommend proper spinal cord decompression and fixation for patients with complete SCI to reduce the chance of secondary SCI.

Management of traumatic posterior fossa epidural hematomas in pediatrics: our experience and review of the literature.

BACKGROUND AND AIMS: Conservative management of posterior fossa epidural hematoma in the pediatric age group has been increasingly considered in the last decade with good clinical outcomes and comparable results to surgical intervention in carefully selected patients. The purpose of this study is to evaluate the outcome of observation in the management of pediatric patients with posterior fossa epidural hematoma (PFEDH) in our tertiary hospital and present a literature review on PFEDH pediatric patients. METHODS: We conducted a retrospective observational study at King Abdullah University Hospital (KAUH), a tertiary hospital in North Jordan. All pediatric patients (≤ 18 years) who were admitted with a diagnosis of PFEDH from January 2010 to December 2020 were included. Demographic data, trauma type, clinical signs and symptoms on admission, CT findings, treatment type, and outcomes were collected and assessed. The outcome was measured using the Glasgow outcome scale (GOS) on discharge from the hospital. RESULTS: A total of 16 patients were identified and included in this study. Nine patients were managed conservatively and 7 surgically. The mean age was 7.7 ± 6 years ranging from 1 to 18 years. Falls were the most common cause of injury. Vomiting was the most frequent presenting symptom. Except for 1 patient, 14 patients had good outcomes with a GOS of 5. One case of mortality was seen in our series. CONCLUSION: Posterior fossa epidural hematoma is a rare clinical condition among the pediatric age group. Early and consecutive CT scans must be obtained for all suspected cases. Successful conservative management can be achieved depending on multiple factors such as hematoma thickness or volume, neurological status on admission, and other radiological findings as shown in our study. The overall prognosis was good in our patients.

The outcome of observation of acute traumatic extradural hemorrhage in pediatric age group.

PURPOSE: The non-operative management of extradural hemorrhage in the pediatric age group has been increasingly considered in the last decade with good clinical outcomes and comparable results to surgical intervention in carefully selected patients. The purpose of this study is to evaluate the outcome of observation in the management of pediatric patients with extra dural hematoma. PATIENTS AND METHODS: All consecutive pediatric patients with traumatic EDH after TBI who were presented to a single neurosurgical institution between January, 2008 and November, 2018 were retrospectively reviewed. Mechanism of injury, Glasgow coma scale (GCS) on admission, presenting neurological examination, treatment modality, the first and last imaging findings, and outcome were analyzed. The outcome was measured using the Glasgow outcome scale (GOS) on discharge from the hospital. RESULTS: A total of 83 patients were identified. The median age was 7.1 years (0.8-14 years) and 67% of the patients were male (n = 56). The median thickness of acute EDH was 1.1 cm (0.2-2.6 cm). 44 patients were managed conservatively with a close observation at a specialized neurotrauma unit for any clinical deterioration, and the remaining 39 patients were managed surgically. There was no significant difference in the patients age, hematoma thickness, presence of skull fractures, systemic injuries, and other types of cerebral injuries between the two groups. The presenting GCS was significantly lower in the surgical group which reflects the severity of the injury. Hospital stay was significantly longer among the surgical group, and the GOS was significantly better in the non-surgical group. The majority of the surgical group showed complete resolution of the hematoma on discharge, while only 50% of the non-surgical patients (n = 22) had a complete resolution of the hematoma one month after the TBI. CONCLUSION: The conservative management is applicable in carefully selected pediatric patients with acute traumatic extradural hematoma provided that the observation is accomplished in a well-established and equipped neurosurgical unit. These results are congruent with similar earlier studies.

Multiple Neural Tube Defects: A Case Report.

BACKGROUND Incomplete closure of the neural tube results in congenital anomalies called neural tube defects (NTD). These defects are rarely multiple, and are characterized by loss of central nervous system soft tissue and bony coverings, along with herniation of the involved part of the CNS through the defect. CASE REPORT A newborn female infant was delivered through planned cesarean section due to large occipital encephalocele diagnosed antenatally. The pregnancy was unplanned and the mother did not take folic acid prior to conception. Birth weight was 3.41 Kg. Upon delivery, the newborn was healthy, with an Apgar score of 8. The physical examination revealed 2 large pouches; one was over the occiput, and the other swelling was located over the nape of the neck. Brain MRI revealed large occipital encephalocele and cervical myelomeningocele. The 2 defects were repaired separately, with an uneventful postoperative course. CONCLUSIONS We report the rare occurrence of multiple NTD. Early repair, either as single or multiple procedures, is mandatory to avoid dramatic complications.

The Safety of Early Thromboembolic Prophylaxis in Closed Traumatic Intracranial Hemorrhage.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with traumatic brain injury (TBI); this study is testing the safety of enoxaparin use for the prevention of venous thromboembolism in this group of patients. PATIENTS AND METHODS: From January 2016 to May 2018, 46 patients (36 males, 10 females) with closed traumatic intracranial bleeding received early (ie, within 72 hours) venous thromboembolic prophylaxis with 40 mg of enoxaparin. Patients with traumatic intracranial hemorrhage were followed up both clinically and with repeated brain computed tomography to examine the safety of enoxaparin VTE prophylaxis. RESULTS: The age of the patients ranged from 16-91 years (43.9±25.8 years). Glasgow coma score ranged from 5-15 (9.9±4.7). Twenty patients had mild TBI (GCS 15-13), 17 patients had moderate TBI (GCS 12-9), and nine patients had severe TBI (GCS≤8). Brain computed tomography showed variable types of brain injuries. Non-surgical management was applied for 18 patients. Craniotomy and surgical evacuation of significant (≥1cm in maximum diameter) EDH and/or SDH was carried out in 26 patients. External ventricular drain was inserted in two patients with significant IVH. Thirty-eight patients had good overall outcome, eight patients showed poor outcome. None of the reviewed patients developed clinical deterioration and/or progression of the intracranial bleeding on follow-up brain CT scans. CONCLUSION: Enoxaparin is a safe prophylaxis against venous thromboembolism in patients with traumatic closed intracranial bleeding.

Outcome of Craniocerebral Penetrating Injuries: Experience from the Syrian War.

OBJECTIVES: Gunshot wounds to the brain are the most fatal of all firearm injuries. The aim of this study was to evaluate mortality and morbidity in patients with penetrating craniocerebral gunshot injuries and to identify risk factors that affect the outcome. PATIENTS AND METHODS: A retrospective review from June 2012 to November 2013 of 44 Syrian patients with gunshot wound to the head was performed. A thorough physical examination and computed tomography (CT) of the brain was obtained for all patients at the time of admission. Associated systemic injuries were found in 19 patients (43%). Surgical intervention was performed in 25 patients (57%); the remaining patients were managed conservatively. The patients were followed for a period of 1 to 15 months (range: 6 ± 2 months). Univariate analysis of patient age, sex, type of penetrating object, Glasgow Coma Scale (GCS) score and pupil size on admission, brain CT findings, presence of systemic injuries, and surgical intervention on the patient outcome was performed. RESULTS: Eleven patients (25%) had a bullet injury; the remaining 33 (75%) patients had blast injuries. Initial brain CT revealed different types of skull fractures, intracerebral hemorrhage, and brain edema in all patients. The mortality rate during the follow-up period was 25%. Of the survivors, 25 patients (76%) had a good recovery, eight patients (24%) had a mild disability, and none had a severe disability. The significant factors determining outcome in this series were GCS on admission (p < 0.005) and positive pupil reaction to light (p < 0.05). The patient age, sex, CT findings, systemic injuries, neurosurgical intervention, and hospital length of stay were not significant prognostic factors (p > 0.05). CONCLUSIONS: Among various variables, GCS and pupil reactivity were the outcome predictors in patients with penetrating craniocerebral injuries. Age, sex, type of penetrating object, CT findings, and surgical intervention did not have a significant effect on survival for these kinds of injuries.

Transplantation of purified autologous leukapheresis-derived CD34+ and CD133+ stem cells for patients with chronic spinal cord injuries: long-term evaluation of safety and efficacy.

This study is aimed at describing a novel method for treating patients with chronic complete spinal cord injuries (SCIs) by utilizing autologous, purified CD34(+) and CD133(+) stem cells (SCs). The study focuses on the safety and efficacy of transplanting unmanipulated, autologous, purified stem cells in treated patients during a 5-year follow-up period. In this report, 19 patients were included (16 males and 3 females) who presented with a complete SCI (ASIA-A) in the thoracic region. The patients' endogenous cells were mobilized with subcutaneous granulocyte-colony-stimulating factor (G-CSF) for 5 days. We utilized the CliniMACS magnetic separation system to purify leukapheresis-derived CD34(+) and CD133(+) SCs. Purified SCs were directly transplanted into the SCI site. Patients were then monitored and followed for up to 5 years. On average, 76 × 10(6) purified SCs were obtained from each patient, with 95.2% purity and >98% viability. SC transplantation into the cyst cavity or the subarachnoid space was successful and well tolerated in all 19 patients and did not cause any allergic or inflammatory reactions within the CNS in the early or late periods after transplantation. Ten patients (53%) showed no improvement after 42-60 months (ASIA-A), while seven patients (37%) demonstrated segmental sensory improvement (ASIA-B), and the remaining two patients (10%) had motor improvement (ASIA-C). This study presents a safe method for transplanting specific populations of purified autologous SCs that can be used to treat SCIs in a clinical setting. The results may be utilized as a stepping-stone for future investigations in the field of regenerative medicine for treatment of SCIs and other neurological diseases. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Endurance exercise training promotes angiogenesis in the brain of chronic/progressive mouse model of Parkinson's Disease.

GOALS AND OBJECTIVES: The main goal of this study is to evaluate the effect of treadmill exercise on the angiogenesis markers in the striatum (ST) of chronic/progressive parkinsonian mice. MATERIALS AND METHODS: Forty 57BL/6 albino mice were randomly divided into four groups. Sedentary control (SC, n=10), exercise control (ExC, n=10), sedentary Parkinson's (SPD, n=10), and exercised Parkinson's (ExPD, n=10). Parkinsonism was induced by the injection with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks, three days and half a part. Following the induction of parkinsonism, ExPD and ExC animal groups were trained on a modified human treadmill at a speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4~weeks. The remaining two groups (SPD and SC) were housed in cages for the same period. At the end of the experiment, the angiogenesis markers; Vascular Endothelial Growth Factor (VEGF) and CD34 were examined in the striatum in the four animal groups. RESULTS: PD resulted in a significant decrease in blood vessel density with the comparison between the sedentary control and PD model animals (p < 0.005). Four weeks of treadmill exercise training significantly increased angiogenesis in the striatum in ExPD groups (p < 0.05). Exercise also induced an increase in blood vessel density in the striatum of the control animals, but the change was not significant (P < 0.3). CONCLUSION: These data suggest that 4 weeks of treadmill exercise promoted angiogenesis in the brain of chronic Parkinsonian mice, which can partially explain the beneficial role exercise in patients with PD. Further studies are required to determine the mechanism of exercise-induced angiogenesis in PD.

Purification of mouse bone marrow-derived stem cells promotes ex vivo neuronal differentiation.

The main objective of this study is to test the potential of specific populations of mouse bone marrow-derived stem cells (BMSCs) to differentiate into the neuronal cell lineage. Bone marrow of 33 mice was aspirated under general anesthesia. The collected marrows were analyzed for cell counts, compositions, and percentages of different stem cell types. We used the Midi MACS magnetic separator to purify specific populations of stem cells from the aspirated bone marrow. Cells were analyzed using flow cytometry. We assessed the presence of stem cell antigen-1 (Sca-1(+)) and prominin-1(+) cells in the cellular fraction that was depleted of lineage-committed cells (lineage(-)). Both purified and nonpurified cells were cultured ex vivo using specific growth media with factors that drive the cells to differentiate into the neuroglial cell types. Cells were then analyzed by flow cytometry for expression of specific neuronal markers. Our results showed that there was an increase of Sca-1(+) and prominin-1(+) cells in the lineage(-) fraction over the unpurified BM. After lineage depletion, the percentages of Sca-1(+) and prominin-1(+) cells increased from 4.9% and 2.6%, up to 76.1% and 59%, respectively. Unpurified mouse BM differentiated into fibroblasts, whereas Sca-1(+) cells were able to generate astrocytes. Interestingly, purified prominin-1(+) cells were able to generate neuronal cells. Purification of adult bone marrow-derived stem cells enhances their potentiality for differentiating into specific neuronal cell lineages.

Conservative management of acute epidural hematoma in a pediatric age group.

OBJECTIVE: Craniotomy and evacuation is the standard treatment of acute epidural hematoma (EDH). Here, the authors report their experience in nonoperative management of acute EDH in children with mild head injury. METHODS: The authors retrospectively reviewed charts of patients with conservatively treated EDH at the Department of Neurosurgery, King Abdulla University Hospital, Irbid, Jordan, between August 2003 and October 2007. All patients had a Glasgow Coma Scale score of 14 or 15, and an initial computerized tomography (CT) scan demonstrating an EDH with or without skull fractures. Follow-up included neurological examination and brain CT. RESULTS: Six children (3 boys, 3 girls) with acute EDH were successfully managed at our department without surgical intervention. The Glasgow Outcome Scale score of all patients was 5, with no posttraumatic sequelae. Follow-up brain CT showed complete resolution of the EDH within 2-3 months. CONCLUSIONS: Our results demonstrated that pediatric EDH can be managed nonoperatively. The pronounced increase in the number of CT examinations for patients with head injuries has resulted in a greater proportion of EDH detected in conscious patients. We recommend such treatment be performed in specialized pediatric neurosurgical centers under close neurological observation.

Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats.

OBJECTIVE: Epidemiological data indicate a high incidence of cerebral aneurysms in postmenopausal women. To elucidate the pathogenesis of cerebral aneurysms, we focused on the contribution of endothelial damage in rats. METHODS: We induced estradiol deficiency by oophorectomy (OVX), hypertension, or both, and hemodynamic stress in 7-week-old female Sprague-Dawley rats. They were then given hormone-replacement therapy with 17beta-estradiol or an angiotensin II type 1 receptor blocker (ARB). The effects of estradiol, angiotensin II type 1 receptor blocker, or both on cultured endothelial cells were also examined. RESULTS: The number of anomalously shaped endothelial cells was higher in OVX than hypertensive rats (P < 0.05). Rats subjected to hypertension and OVX exhibited a marked increase in the incidence of saccular cerebral aneurysms. Estradiol or angiotensin II type 1 receptor blocker treatment reduced this incidence (P < 0.05). The endothelial nitric oxide synthase (eNOS) mRNA level in the intracranial artery of OVX and hypertensive and OVX rats was low (P < 0.05). Immunohistochemically, the expression of eNOS and estrogen receptor alpha (ERalpha) in the vascular wall of hypertensive and OVX rats was decreased; angiotensin II and the nicotinamide adenine dinucleotide phosphate oxidase subunits nicotinamide adenine dinucleotide phosphate oxidase 4 and p22phox were strongly expressed in cerebral aneurysms. In the absence of estradiol, eNOS was downregulated and nicotinamide adenine dinucleotide phosphate oxidase expression was increased in endothelial cells; angiotensin II augmented these phenomena. The regulation of eNOS was mediated by ERalpha. These results suggest that estrogen deficiency induces endothelial dysfunction and reactive oxygen species generation, triggering endothelial damage that leads to cerebral aneurysms and that hypertension is an additional risk factor. CONCLUSION: A therapy targeted at the endothelium and management of hypertension may help to prevent cerebral aneurysms.

Collateral blood flow patterns in patients with unilateral ICA agenesis and cerebral aneurysm.

BACKGROUND: Agenesis of one or both internal carotid arteries (ICA) is usually a benign congenital anomaly. Many patients are diagnosed incidentally and remain asymptomatic, however associated cerebral aneurysms can be life-threatening and result in high morbidity and mortality rates in this population. MATERIAL & METHODS: Based on the timing of ICA agenesis, during the fetal life, we classified the collateral blood flow pattern into three major types; type I: Collateral blood flow via primitive vessels, type II: Collateral blood flow via ICA branches, and type III: collateral blood flow via branches of the external carotid artery (ECA). The type of collateral blood flow pattern in the reported patients with ICA agenesis and cerebral aneurysm was reviewed in order to determine the relation between the type of collateral blood flow and the development of CAs. RESULTS: Twenty nine patients with ICA agenesis and CA were reported, of these 27 patients (93%) were found to have type II collateral blood flow, 2 patients (7%) had type I collateral blood flow pattern and none had type III collateral flow pattern. The majority of patients (79%) with CA secondary to ICA agenesis presented with subarachinoid hemorrhage (SAH). CONCLUSION: Although ICA agenesis is a symptomatic in the majority of cases, it must be recognized because it promotes the development of CA and SAH. Our new classification system for collateral blood flow patterns is easy to use and can predict those at high risk to develop cerebral aneurysms and SAH, and therefore, need annual screening MRA.

Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats.

OBJECT: Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. METHODS: The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague-Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery-olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohistochemically by using antibodies against endothelial nitric oxide synthase, alpha-smooth muscle actin, macrophages, and matrix metalloproteinase-9. RESULTS: Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). CONCLUSIONS: This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.

Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part I: experimental study of the effect of oophorectomy in rats.

OBJECT: Estrogen has been shown to play a central role in vascular biology. Although it may exert beneficial vascular effects, its role in the pathogenesis of cerebral aneurysms remains to be determined. To elucidate the role of hormones further, the authors examined the effects of bilateral oophorectomy on the formation and progression of cerebral aneurysms in rats. METHODS: Forty-five female, 7-week-old Sprague-Dawley rats were divided into three equal groups. Group I consisted of intact rats (controls). To induce cerebral aneurysms, the animals in Groups II and III were subjected to ligation of the right common carotid and bilateral posterior renal arteries. One month later, the rats in Group II underwent bilateral oophorectomy. Three months after the experiment began all animals were killed and cerebral vascular corrosion casts were prepared and screened for cerebral aneurysms by using a scanning electron microscope. Plasma was used to determine the level of estradiol and the gelatinase activity. Hypertension developed in all rats except those in the control group. The estradiol level was significantly lower in Group II than in the other groups (p < 0.01). The incidence of cerebral aneurysm formation in Group II (60%) was three times higher than that in Group III (20%), and the mean size of aneurysms in Group II (76 +/- 27 microm, mean +/-standard deviation) was larger than that in Group III (28 +/- 4.6 microm) (p < 0.05). No aneurysm developed in control animals (Group I), and there was no significant difference in plasma gelatinase activity among the three groups. CONCLUSIONS: The cerebral aneurysm model was highly reproducible in rats. Bilateral oophorectomy increased the susceptibility of rats to aneurysm formation, indicating that hormones play a role in the pathogenesis of cerebral aneurysms.

Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II: experimental study of the effects of hormone replacement therapy in rats.

OBJECT: The increased incidence of cerebral aneurysms in postmenopausal women appears to be related to low levels of circulating estrogen. Using a rat model of aneurysm induction, the authors found that oophorectomy increased the incidence of experimental cerebral aneurysms (Part I in this issue). In the current study they examined the effects of hormone replacement therapy (HRT) on the formation of cerebral aneurysms in rats. METHODS: Forty-five female Sprague-Dawley rats were divided into three equal groups. The animals in Groups A and B were subjected to a cerebral aneurysm induction procedure (renal hypertension and right common carotid artery ligation) followed 1 month later by bilateral oophorectomy. After an additional week the rats in Group A received 17beta estradiol continuous-release pellets. The rats in Group C served as controls. Three months after the aneurysm induction procedure, all the rats were killed and vascular corrosion casts of their cerebral arteries were prepared and checked for aneurysmal changes. Using a scanning electron microscope, the authors recorded aneurysmal changes as endothelial changes alone (Stage I), endothelial changes with intimal pad elevation (Stage II), and saccular aneurysm formation (Stage III). Aneurysmal changes (Stages I, II, and III) occurred in one third of rats that had undergone oophorectomy and were receiving HRT (Group A), compared with 87% of the rats that had undergone oophorectomy but did not receive HRT (Group B). Although most of the aneurysmal changes identified in Group A rats were limited to Stage I or II, most changes in Group B animals were identified as saccular dilation (Stage III). CONCLUSIONS: The findings demonstrated the significant protective role of estrogen against the formation and progression of cerebral aneurysms. It appears to be related to the beneficial effects of estrogen on the function and growth of endothelial cells, which play a major role in preserving the integrity of the vascular wall.

Vascular corrosion casts mirroring early morphological changes that lead to the formation of saccular cerebral aneurysm: an experimental study in rats.

OBJECT: The formation of cerebral aneurysms involves complex processes and little is known about the mechanisms by which they originate, grow, and rupture. The purpose of this study was to identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysms. METHODS: Twenty male Sprague-Dawley rats were subjected to cerebral aneurysm induction (renal hypertension and right common carotid artery ligation); 10 intact rats served as the control group. The animals were killed after 2 months, and a vascular corrosion cast of their cerebral arteries was prepared and screened for aneurysm development by using a scanning electron microscope. Sequential morphological changes observed at the cerebral artery bifurcation in response to hemodynamic shear stress included endothelial changes, intimal pad elevation, and saccular dilation. Endothelial cell changes were the first observed morphological changes; they were followed by various degrees of artery wall dilation. No aneurysmal changes developed in any of the control rats. Of the 20 surgically treated rats, 11 displayed aneurysmal changes. In five of these animals only changes in the endothelial cell imprints could be identified. In the other six rats morphological changes in endothelial cells were associated with different stages of aneurysmal dilation. CONCLUSIONS: This is the first study to demonstrate in vivo early morphological changes that lead to the formation of cerebral aneurysms. The morphological findings indicate the principal role of endothelial cells in the pathogenesis of cerebral aneurysms and suggest that hemodynamic shear stress and blood flow patterns may precipitate these early changes.