Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review.

Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.

Use of fluorescein sodium-assisted intraoperative sample validation to maximize the diagnostic yield of stereotactic brain biopsy: progress toward a new standard of care?

OBJECTIVE: In patients with contraindication to open resection, histological diagnosis is obtained through a stereotactic biopsy (SB). Missed diagnoses and sampling errors are important limitations of SB; therefore, various ways have been proposed to increase the diagnostic yield (DY). Intraoperative histopathology can obtain a DY exceeding 98% but with several drawbacks, namely prolonged operative times and logistic concerns. The objective of this study was to evaluate whether intraoperative validation of samples with fluorescein sodium can obtain a high DY with the same ease of use as standard SB. METHODS: One hundred three consecutive cases of frameless neuronavigated SB performed at the authors' center from May 2013 to June 2021 were included. Two groups were compared: 46 patients underwent standard nonassisted SB (nSB), and 57 patients underwent fluorescein sodium-assisted SB (fSB). Data were collected retrospectively before 2017 and prospectively thereafter. DY, operative time, and rate of complications were compared between the two groups. The surgical technique for fSB was standardized, and a novel classification system for intraoperative fluorescence findings was developed. RESULTS: Statistically significant differences between the two groups were identified. The DY of the fSB group (100%, 95% CI 93.73%-100%) was significantly greater than that of the nSB group (89.13%, 95% CI 80.14%-98.13%) (p = 0.0157). No statistically significant differences were observed in terms of mean operative time (p = 0.7104), intraoperative complications (p = 0.999), or postoperative complications (p = 0.5083). CONCLUSIONS: Compared with standard nSB, fSB showed a significantly higher DY and similar surgical time and rate of complications. The ease of use, wide diagnostic spectrum, and low cost make fluorescein sodium preferable to other fluorophores. The present study strengthens the limited data in the literature indicating routine use of fSB. The proposed workflow suggests that fSB should be the standard of care for contrast-enhanced cases. Intraoperative histopathology should be limited to nonenhancing cases, and nSB should be avoided. Future prospective multicenter studies will be useful for further validation of our findings.

Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas.

OBJECTIVE: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. METHODS: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from -1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. RESULTS: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). CONCLUSIONS: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.

Dissecting Aneurysm of the L1 Radiculomedullary Artery Associated with Subarachnoid Hemorrhage: A Case Report.

BACKGROUND: Both spinal artery aneurysm and spinal subarachnoid hemorrhage represent a very rare event. METHODS: We report a case of a ruptured dissecting aneurysm of the right L1 radiculomedullary artery associated with subarachnoid hemorrhage and severe motor weakness. RESULTS: An urgent decompressive hemilaminectomy was performed due to worsening in motor deficit. A subsequent spinal angiography showed a dissection of radiculomedullary artery of L1 on the right side, treated conservatively. CONCLUSION: Nowadays, therapeutic strategies for this aneurysm remain controversial. Conservative strategy can represent a valid alternative.

Intracranial Pressure Monitoring in Poor-Grade Patients with Aneurysmal Subarachnoid Hemorrhage Treated by Coiling.

OBJECTIVE: The main objective of the present study was to analyze the intracranial pressure (ICP) and cerebral perfusion pressure (CPP) changes during coiling. We also evaluated the prevalence of rebleeding and outcomes for patients monitored before and after coiling. METHODS: Ninety-nine consecutive poor-grade patients with aneurysmal subarachnoid hemorrhage (aSAH; World Federation of Neurological Surgeons grade IV and V) were enrolled in our prospective observational study. For 31 patients, ICP and CPP monitoring was started immediately after the diagnosis of aSAH, and the values were recorded every 15 minutes during coiling (early ICP group). For 68 patients, ICP and CPP monitoring began after coiling (late ICP group). The outcomes were evaluated at 90 days using the modified Rankin scale. RESULTS: At the beginning of coiling, the ICP was >20 mm Hg in 10 patients (35.7%). The median ICP was 18 mm Hg (range, 5-60 mm Hg). The CPP was <60 mm Hg in 6 patients (24%). The median CPP was 70 mm Hg (range, 30-101 mm Hg). Despite medical treatment and/or cerebrospinal fluid drainage, 51.6% of the patients monitored during coiling had at least one episode of intracranial hypertension (defined as ICP >20 mm Hg), and 51.6% had at least one episode of reduced CPP (defined as CPP <60 mm Hg). Early monitoring (before aneurysm repair) was not associated with rebleeding. At 90 days, the functional recovery was better in the early ICP group (P = 0.004). CONCLUSIONS: During coiling, patients with poor-grade aSAH can experience episodes of intracranial hypertension and reduced CPP. Early and appropriate treatment of elevated ICP was not associated with rebleeding and might have improved the outcomes.

Choroid Plexus Carcinoma in Adults: Literature Review and First Report of a Location into the Third Ventricle.

Choroid plexus carcinoma (CPC) is a rare intraventricular neoplasm originating from choroid plexus. CPC is the most aggressive choroid plexus tumor. Almost all the CPCs are detected in children, and the preferred location is the lateral ventricle. We reviewed the literature to evaluate the state of the art concerning the management of CPC in adults and report the first case described of the extremely rare localization into the third ventricle. A 38-year-old woman presented a medical history of Parinaud syndrome and occasional facial weakness. Brain magnetic resonance imaging revealed a mass lesion in the pineal region and posterior part of the third ventricle with obstructive hydrocephalus. She underwent subtotal resection through a supracerebellar infratentorial approach. After the histopathological diagnosis of CPC, the patient underwent a second surgery with gross total resection and adjuvant radiotherapy. CPC in adults, given its extreme rarity, does not have a standardized treatment. Gross total resection should be the first step of the treatment: however, according to the literature, gross total resection is achieved only in 40-75% of cases in CPC as opposed to 95% in choroid plexus papilloma, mainly due to the difficulty in managing a highly vascularized tumor in such a deep location. Chemotherapy has not an established role and adjuvant treatment is based on radiotherapy. In the case described hereby the gross total resection associated with surgical treatment of hydrocephalus and adjuvant radiotherapy has achieved a good clinical and radiological outcome.

Posttraumatic Middle Meningeal Artery Pseudoaneurysm: Case Report and Review of the Literature.

BACKGROUND: Intracranial pseudoaneurysm is a rare entity, with few cases described in the literature, and is mostly associated with a history of traumatic brain injury. Traumatic aneurysms comprise <1% of all intracranial aneurysms. In particular, middle meningeal artery (MMA) aneurysms are uncommon and usually caused by a skull fracture in the temporal region. About 40 traumatic MMA aneurysms are reported in the literature, and only 28 nontraumatic aneurysms are reported, usually related to high-flow conditions. The behavior of these aneurysms is largely unknown: both spontaneous resolution and aneurysm growth, leading to subsequent rupture, have been reported. Surgical and endovascular management are feasible for MMA aneurysms; however, the criterion standard treatment is not defined. CASE DESCRIPTION: We report the case of a traumatic pseudoaneurysm of the right MMA treated with an endovascular approach and provide a review of the literature. CONCLUSIONS: Aneurysms of the MMA are a rare entity that must be taken into account in the setting of a traumatic brain injury or predisposing factors. The diagnosis and aggressive treatment are mandatory, preventing the devastating consequences of their rupture. Endovascular and surgical techniques are well defined and available, even though there is not a demonstrated superiority in any of them.

Rare Case of Dumbbell-Shaped Spinal Cavernous Hemangioma and Literature Review.

BACKGROUND: Spinal epidural cavernous hemangiomas are rare vascular malformations. Exceptionally, they present with dumbbell-shaped morphology. When they happen, it's mandatory to include their pathology in the differential diagnosis because of their similarity to schwannomas. CASE DESCRIPTION: We report the case of a 72-year-old woman with a dumbbell-shaped thoracic epidural cavernous hemangioma. A literature review of diagnostic features and current treatment options are also discussed. CONCLUSIONS: Surgery is safe and effective in both improving patient condition and preventing acute hemorrhage that can worsen the outcome, causing neurologic and potentially irreversible deficits. The favorable result we obtained in our patient suggests that surgery should be evaluated as the first option, even in patients with large epidural cavernous hemangiomas.

Translaminar Approach for Treatment of Hidden Zone Foraminal Lumbar Disc Herniations: Surgical Technique and Preoperative Selection of Patients with Long-Term Follow-Up.

BACKGROUND: Lumbar disc herniation is a common degenerative disease of the lumbar spine with a prevalence of 1%-3% in some population studies. In 10% of patients, there is a fragment migrated cranially in Macnab's "hidden zone." In selected cases, this fragment can be removed with a translaminar approach that was described in 1998. We provide a detailed description of the technical advantages and pitfalls of the translaminar approach in a consecutive series of 32 patients treated at our institution. METHODS: Patients were divided preoperatively and postoperatively into 5 classes based on the Oswestry Disability Index (ODI): class 1, ODI 0%-20% (minimal disability); class 2, 20%-40% (moderate disability); class 3, 40%-60% (severe disability); 60%-80% (crippled); 80%-100% (bedridden or disabling symptoms). RESULTS: Four (12.5%) patients were upgraded 1 ODI class after the operation; 6 (18.7%) patients were upgraded 2 classes, 8 (25%) patients were upgraded 3 classes, and 11 (34.4%) patients were upgraded 4 classes. In 3 (9.4%) patients, ODI class did not change after the operation. After surgery, 7 (21.9%) patients developed mild low back pain. Mean follow-up was 25 months. CONCLUSIONS: When performed by dedicated spinal neurosurgeons, the translaminar approach is safe and effective in patients with long-term follow-up. Most patients showed an improvement in ODI. Major pitfalls were related to surgical selection and the narrow working space.

Detailed anatomy knowledge: first step to approach petroclival meningiomas through the petrous apex. Anatomy lab experience and surgical series.

Petroclival meningiomas are a challenge for neurosurgeons due to the complex anatomy of the region that is rich of vessels and nerves. A perfect and detailed knowledge of the anatomy is very demanding in neurosurgery, especially in skull base surgery. The authors describe the microsurgical anatomy to perform an anterior petrosectomy based on their anatomical and surgical experience and perform a literature review. The temporal bone is the most complex and fascinating bone of skull base. The apex is located in the angle between the greater wing of the sphenoid and the occipital bone. Removing the petrous apex exposes the clivus. The approach directed through the temporal bone in this anatomical area is referred to as an anterior petrosectomy. The area that must be drilled is the rhomboid fossa that is defined by the Kawase, premeatal, and postmeatal triangles. In Division of Neurosurgery - University of Turin, 130 patients, from August 2013 to September 2015, underwent surgical resection of intracranial meningiomas. In this group, we have operated 7 PCMs and 5 of these were approached performing an anterior petrosectomy with good results. In our conclusions, we feel that this surgery require an advanced knowledge of human anatomy and a specialized training in interpretation of radiological and microsurgical anatomy both in the dissection lab and in the operating room.

Role of nitric oxide and mechanisms involved in cerebral injury after subarachnoid hemorrhage: is nitric oxide a possible answer to cerebral vasospasm?

Cerebral vasospasm represents the most critical event that could occur after subarachnoid hemorrhage (SAH). Therapy is only partially effective because cerebral arterial constriction is not fully understood yet. One of the most important biological messenger associated to SAH is nitric oxide (NO), that is considered local regulator of cerebral blood flow. Different nitric oxide synthase (NOS) forms play a role in different biological processes, one of which is to link neuronal activity to blood flow in cerebral cortex. We performed a reassessment of the literature to summarize the role of NO as the main inflammatory pathway activated after SAH to clarify its importance for treatment of vasospasm.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.

The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms.

OBJECT: Vasopressor-induced hypertension (VIH) is an established treatment for patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and delayed cerebral ischemia (DCI). However, the safety of VIH in patients with coincident, unruptured, unprotected intracranial aneurysms is uncertain. METHODS: This retrospective multiinstitutional study identified 1) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH group). All patients had previously undergone surgical or endovascular treatment for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH patients were made in terms of the patient characteristics, clinical and radiographic severity of SAH, total number of aneurysms, number of ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia, and degree and duration of VIH therapy. RESULTS: For the VIH group (n = 176), 484 aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114 unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the mean sizes of the ruptured (7.2 ± 0.3 vs 7.8 ± 0.6 mm, respectively; p = 0.27) and unruptured (3.4 ± 0.2 vs 3.2 ± 0.2 mm, respectively; p = 0.40) aneurysms did not differ. The authors observed 1 new SAH from a previously unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p = 0.50). Baseline patient characteristics and comorbidities were similar between groups. While the degree of hypervolemia was similar between the VIH and non-VIH patients (fluid balance over the first 10 days of therapy: 3146.2 ± 296.4 vs 2910.5 ± 450.7 ml, respectively; p = 0.67), VIH resulted in a significant increase in mean arterial pressure (mean increase over the first 10 days of therapy relative to baseline: 125.1% ± 1.0% vs 98.2% ± 1.2%, respectively; p < 0.01) and systolic blood pressure (125.6% ± 1.1% vs. 104.1% ± 5.2%, respectively; p < 0.01). CONCLUSIONS: For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during VIH therapy is rare. The authors do not recommend withholding VIH therapy from these patients.

Say "no" to spinal cord injury: is nitric oxide an option for therapeutic strategies?

PURPOSE: a literature review was made to investigate the role of nitric oxide (NO) in spinal cord injury, a pathological condition that leads to motor, sensory, and autonomic deficit. Besides, we were interested in potential therapeutic strategies interfering with NO mechanism of secondary damage. MATERIALS: A literature search using PubMed Medline database has been performed. RESULTS: excessive NO production after spinal cord injury promotes oxidative damage perpetuating the injury causing neuronal loss at the injured site and in the surrounding area. CONCLUSION: different therapeutic approaches for contrasting or avoiding NO secondary damage have been studied, these include nitric oxide synthase inhibitors, compounds that interfere with inducible NO synthase expression, and molecules working as antioxidant. Further studies are needed to explain the neuroprotective or cytotoxic role of the different isoforms of NO synthase and the other mediators that take part or influence the NO cascade. In this way, it would be possible to find new therapeutic targets and furthermore to extend the experimentation to humans.

Cerebrovascular diseases in the elderly: the challenge of multiple aneurysms.

OBJECTIVE: The worldwide population aging and the nowadays medical advances impose to consider new management guidelines for elderly. Aim of this study was to assess the best treatment in elderly with multiple intracranial aneurysms (MIA). METHODS: From 1994 to 2011, we admitted 1462 patients with ruptured cerebral aneurysm. Among those aged ≥65 years, 43 had MIA (15% of elderly). Size and aneurysm location, timing and type of treatment were analyzed. Patients were thus stratified according to Hunt-Hess grade on admission and evaluated at 6 months using the Glasgow Outcome Scale (GOS). RESULTS: We had 87 aneurysms in the final series. Three patients died because of the impossibility to treat the ruptured aneurysm. No new bleeding from untreated aneurysms was observed; no retreatment after previous coiling was performed. CONCLUSIONS: MIA lead to significantly poorer outcomes, especially in elderly, because of their general clinical condition, presence of risk factors and lower capacity of reaction to stressful events. In patients without large hematomas, coiling of the ruptured aneurysm represents the procedure with high effectiveness. The clinical conditions on admission represent the most important factor for the treatment results. To reduce the treatment-related risks we do recommend a conservative approach for the unruptured aneurysms.

Acute branch occlusion after Pipeline embolization of intracranial aneurysms.

Flow-diverters are used in the treatment of large and complex intracranial aneurysms. One major concern with this concept is the potential for compromise of side branches and perforators covered by the device. We describe three patients treated with the Pipeline embolization device (PED; ev3 Endovascular, Plymouth, MN, USA) who developed immediate compromise of flow into an eloquent side branch covered by the device. Three patients, two with giant posterior circulation aneurysms and one with recurrence of a previously clipped and subsequently coiled middle cerebral artery aneurysm, were each treated by placement of a single PED. Shortly after placement of the devices, despite adequate antiplatelet and anticoagulation regimens, partial or complete occlusion of a major side branch occurred. In all three patients, the occlusion was promptly reversed with intra-arterial administration of abciximab with no clinical sequelae. These cases are concerning because branch occlusion occurred even in the setting of patients appropriately premedicated with dual antiplatelet therapy and in whom genetic testing suggested clopidogrel responsiveness. Close monitoring of patients treated with these devices is critical to establish the frequency of this and other unanticipated complications.

Intracranial aneurysms in patients with internal carotid artery occlusion: management and outcome in 22 cases.

BACKGROUND: There is little information about clinical characteristics, management, and outcome of patients with intracranial aneurysms and internal carotid artery occlusion. We will describe clinical characteristics, treatment and outcome of patients with coexistent internal carotid artery occlusion and intracranial aneurysms. METHODS: We conducted a retrospective chart review of 22 patients (eight males and 14 females) with coexistent internal carotid artery (ICA) occlusion and intracranial aneurysms. RESULTS: This series includes 14 females and eight males with a mean age of 63 years (range, 49 to 80). These patients harbored a total of 35 aneurysms, which were located on the same side of the ICA occlusion in five cases, on the contralateral side in 20 cases, while in ten cases the aneurysm had a midline location (AcomA 9, Basilar tip 1). Treatment consisted of surgery for eight aneurysms and endovascular embolization for 13 aneurysms. No invasive treatment was recommended for 14 aneurysms (eight patients with single aneurysm). No permanent perioperative or periprocedural complications occurred in the selected group of patients undergoing invasive treatment. At a mean follow-up of 57 months (range, 3-203), no patient had a subarachnoid hemorrhage and three patients had died of causes not related to the aneurysm. CONCLUSION: Surgical and endovascular treatment can be accomplished safely in selected patients with coexistent ICA occlusion and intracranial aneurysms. Conservative treatment is a valid alternative, especially in elderly patients or in patients with very small aneurysms, especially if not located along the collateral pathway.