Unruptured cerebral aneurysms in elderly patients: key challenges and management.

Unruptured cerebral aneurysms are increasingly identified in elderly patients as the global life expectancy continues to rise and non-invasive vascular imaging becomes more prevalent. The optimal management of unruptured aneurysms in elderly patients remains controversial. Variability in life expectancy, comorbidities and rupture risk coupled with heterogenous endovascular and surgical treatments contribute to a paucity of clear guidelines, and current management is highly individualized. Elderly patients present unique considerations including frailty, cognitive dysfunction, vasculopathy, reduced life expectancy and overall worse prognosis in case of rupture which shape the risks and likelihood of success of endovascular and microsurgical treatment. In this review, we provide a comprehensive overview of unruptured cerebral aneurysms in the elderly, with a particular focus on the natural history, key challenges associated with advanced age, management and future innovations to further refine treatment.Key MessagesThe management of unruptured cerebral aneurysms in elderly patients remains controversial.Key challenges including frailty, cognitive dysfunction, reduced life expectancy, vasculopathy and poor prognosis with aneurysm rupture add complexity to endovascular and surgical decision making not encountered with younger demographics.A thorough understanding of available treatment options, likelihood of treatment success and associated risks weighed against the risk of aneurysm rupture informs patient discussion and management.

When the Blood Hits Your Brain: The Neurotoxicity of Extravasated Blood.

Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked. Since trials of surgical intervention to remove CNS hemorrhage have been generally unsuccessful, the potent neurotoxicity of blood is generally viewed as a basic scientific curiosity rather than a clinically meaningful factor. In this review, we evaluate the direct role of blood as a neurotoxin and its subsequent clinical relevance. We first describe the molecular mechanisms of blood neurotoxicity. We then evaluate the clinical literature that directly relates to the evacuation of CNS hemorrhage. We posit that the efficacy of clot removal is a critical factor in outcome following surgical intervention. Future interventions for CNS hemorrhage should be guided by the principle that blood is exquisitely toxic to the brain.

Efficacy of Early (≤ 24 Hours), Late (25-72 Hours), and Delayed (>72 Hours) Surgery with Magnetic Resonance Imaging-Confirmed Decompression in American Spinal Injury Association Impairment Scale Grades C and D Acute Traumatic Central Cord Syndrome Caused by Spinal Stenosis.

The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the t test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. During a 19-year period, 101 patients with ATCCS, admission ASIA Impairment Scale (AIS) grades C and D, and an admission AMS of ≤95 were surgically decompressed. Twenty-four of 101 patients had an AIS grade C injury. Eighty-two patients were males, the mean age of patients was 57.9 years, and 69 patients had had a fall. AMS at admission was 68.3 (standard deviation [SD] 23.4); upper extremities (UE) 28.6 (SD 14.7), and lower extremities (LE) 41.0 (SD 12.7). AMS at the latest follow-up was 93.1 (SD 12.8), UE 45.4 (SD 7.6), and LE 47.9 (SD 6.6). Mean number of stenotic segments was 2.8, mean canal compromise was 38.6% (SD 8.7%), and mean intramedullary lesion length (IMLL) was 23 mm (SD 11). Thirty-six of 101 patients had decompression within 24 h, 38 patients had decompression between 25 and 72 h, and 27 patients had decompression >72 h after injury. Demographics, etiology, AMS, AIS grade, morphometry, lesion length, surgical technique, steroid protocol, and follow-up AMS were not statistically different between groups treated at different times. We analyzed the effect size of timing of decompression categorically and in a continuous fashion. There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21; p = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.

Viral therapies for glioblastoma and high-grade gliomas in adults: a systematic review.

OBJECTIVE: High-grade gliomas (HGGs) inevitably recur and progress despite resection and standard chemotherapies and radiation. Viral therapies have emerged as a theoretically favorable adjuvant modality that might overcome intrinsic factors of HGGs that confer treatment resistance. METHODS: The authors present the results of systematic searches of the MEDLINE and ClinicalTrials.gov databases that were performed for clinical trials published or registered up to July 15, 2020. RESULTS: Fifty-one completed clinical trials were identified that made use of a virus-based therapeutic strategy to treat HGG. The two main types of viral therapies were oncolytic viruses and viral vectors for gene therapy. Among clinical trials that met inclusion criteria, 20 related to oncolytic viruses and 31 to gene therapy trials. No oncolytic viruses have progressed to phase III clinical trial testing, although there have been many promising early-phase results and no reported cases of encephalitis or death due to viral therapy. Three phase III trials in which viral gene therapy was used have been completed but have not resulted in any FDA-approved therapy. Recent efforts in this area have been focused on the delivery of suicide genes such as herpes simplex virus thymidine kinase and cytosine deaminase. CONCLUSIONS: Decades of research efforts and an improving understanding of the immunomodulatory effects of viral therapies for gliomas are informing ongoing clinical efforts aimed at improving outcomes in patients with HGG. The available clinical data reveal varied efficacy among different virus-based treatment strategies.

Use of viscoelastic monitoring and prothrombin complex concentrate in a paediatric patient with polytrauma and severe traumatic brain injury.

Viscoelastic monitoring (VEM) tools, such as rotational thrombelastometry, have been used extensively to measure coagulopathy in adults but have received less attention in paediatric care. The presented case involves a 5-year-old boy who was brought to the emergency department after a motor vehicle collision with a Glasgow Coma Scale score of 6T and extensive injuries, including a subdural hematoma. VEM was used to monitor the patient's coagulopathy and to inform treatment measures by allowing real-time visualisation of the patient's coagulation status. VEM was additionally used to direct blood product replacement in preparation for neurosurgical intervention, and 4-factor prothrombin complex concentrate (PCC) was used to help reverse the coagulopathy. The patient underwent successful hemicraniectomy after improvement of his coagulopathy. In paediatrics, VEM and PCC are increasingly being used for post-trauma coagulopathy, and this case highlights their potential promise and the need for further research.

Demographic age-related variation in Circle of Willis completeness assessed by digital subtraction angiography.

OBJECTIVE: Incomplete circle of Willis (CoW) configuration is an important risk factor for cerebrovascular pathology, namely aneurysm formation and ischemic stroke. This study was performed to characterize CoW variation using digital subtraction angiography and to identify demographic and physiologic features that may influence the risk of having an incomplete CoW configuration. MATERIALS AND METHODS: A retrospective review of 274 patients who underwent cerebral angiography by a single surgeon for any indication was conducted. Each CoW branch was graded as normal, hypoplastic, or aplastic. Univariate and multivariate regression analyses were conducted to assess the impact of age, gender, race, and certain comorbidities on CoW configuration. RESULTS: A complete CoW was identified in 37.23% of patients. In univariate analysis, patients <40 years old were more likely to have a complete CoW (odds ratio [OR]: 4.973, 95% confidence interval [CI]: 2.610-9.476, P < 0.001) as were patients <70 years old (OR: 2.849, 95% CI: 1.131-7.194, P < 0.05). Univariate analysis on demographic factors and comorbidities revealed CoW completeness to decrease with hypertension (OR: 0.575, 95% CI: 0.347-0.951, P = 0.031) and diabetes mellitus (OR: 0.368, 95% CI: 0.180-0.754, P = 0.006). Multivariable logistic regression analysis used to assess the impact of age on CoW completeness showed age to be an independent predictor of complete CoW, with an inverse correlation between increasing age and CoW completeness (OR: 0.955, 95% CI: 0.937-0.973, P < 0.001) after controlling for potential confounders including hypertension and diabetes mellitus. CONCLUSIONS: CoW configuration shows considerable variation with age; however, further investigation is required to elucidate the full impact of other demographic and vascular risk factors on CoW anatomy.

Pipeline embolization device for recurrence of previously treated aneurysms.

OBJECTIVE The utilization of the Pipeline embolization device (PED) has increased significantly since its inception and original approval for use in large, broad-necked aneurysms of the internal carotid artery. While microsurgical clipping and advances in endovascular techniques have improved overall efficacy in achieving complete occlusion, recurrences still occur, and the best modality for retreatment remains controversial. Despite its efficacy in this setting, the role of PED utilization in the setting of recurrent aneurysms has not yet been well defined. This study was designed to assess the safety and efficacy of PED in the recurrence of previously treated aneurysms. METHODS The authors reviewed a total of 13 cases in which patients underwent secondary placement of a PED for aneurysm recurrence following prior treatment with another modality. The PEDs were used to treat aneurysm recurrence or residual following endovascular coiling in 7 cases, flow diversion in 2, and microsurgical clipping in 4. The mean time between initial treatment and retreatment with a PED was 28.1 months, 12 months, and 88.7 months, respectively. Clinical outcomes, including complications and modified Rankin Scale (mRS) scores, and angiographic evidence of complete occlusion were tabulated for each treatment group. RESULTS All PEDs were successfully placed without periprocedural complications. The rate of complete occlusion was 80% at 6 months after PED placement and 100% at 12 months in these patients who underwent PED placement following failed endovascular coiling; there were no adverse clinical sequelae at a mean follow-up of 26.1 months. In the 2 cases in which PEDs were placed for treatment of residual aneurysms following prior flow diversion, 1 patient demonstrated asymptomatic vessel occlusion at 6 months, and the other exhibited complete aneurysm occlusion at 12 months. In patients with aneurysm recurrence following prior microsurgical clipping, the rate of complete occlusion was 100% at 6 and 12 months, with no adverse sequelae noted at a mean clinical follow-up of 27.7 months. CONCLUSIONS The treatment of recurrent aneurysms with the PED following previous endovascular coiling, flow diversion, or microsurgical clipping is associated with a high rate of complete occlusion and minimal morbidity.