Aneuploidy in Cancer and Aging.

Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship. Additionally, we provide a comprehensive overview of the function and regulation of the anaphase-promoting complex, an E3 ubiquitin ligase that mediates high-fidelity chromosome segregation, and describe the mechanisms that lead to whole-chromosome gain or loss. With this review, we aim to expand our understanding of the role of CIN in cancer and aging with the long-term objective of harnessing this information for the advancement of patient care.

Small symptomatic anterior communicating artery aneurysms: report of three cases and literature review.

PURPOSE: Given the anatomical relationship between the ACom complex and the optic nerve, small aneurysms of the ACom can present with visual symptoms. CASE REPORTS: We summarize and illustrate the clinical course of three patients with symptomatic small ACom aneurysms and collect similar other cases reported. RESULTS: Ten patients with small unruptured visually symptomatic anterior communicating artery aneurysms were found in the literature. Including three patients herein reported, the mean age at presentation was 56. The most common visual symptoms were bitemporal vision loss and/or a decrease in visual acuity. CONCLUSION: Unruptured aneurysms of the anterior communicating artery can present with visual symptoms due to compression of optic pathways, even at a small size. Prompt recognition and treatment of such a condition are paramount as new onset of visual symptoms can signify impending rupture akin to small PCom aneurysms compressing the third nerve. We discuss a few pitfalls of clipping small ACom aneurysms compressing the optic nerve.

Long-term outcomes following pipeline embolization of unruptured aneurysms.

BACKGROUND: Flow diversion using the pipeline embolization device (PED) for unruptured aneurysms is associated with high occlusion and low morbidity and mortality. However, most reports have limited follow-up of 1-2 years. Therefore, we sought to report our outcomes after PED for unruptured aneurysms in patients with at least 5-years of follow-up. METHODS: Review of patients undergoing PED for unruptured aneurysms from 2009 to 2016. RESULTS: Overall, 135 patients with 138 aneurysms were included for analysis. Seventy-eight percent of aneurysms (n=107) over a median radiographic follow-up of 5.0 years underwent complete occlusion. Among aneurysms with at least 5-years of radiographic follow-up (n=71), 79% (n=56) achieved complete obliteration. No aneurysm recanalized after radiographic obliteration. Furthermore, over a median clinical follow-up period of 4.9 years, 84% of patients (n=115) self-reported mRS scores between 0 and 2. For patients with at least 5-years of clinical follow-up, 88% (n=61) reported mRS between 0 and 2. In total, 3% (n=4) of patients experienced a major, non-fatal neurologic complication related to the PED, 5% (n=7) of patients experienced a minor neurologic complication related to PED placement, and 2% (n=3) died from either delayed aneurysm rupture, delayed ipsilateral hemorrhage after PED placement, or delayed (9 months after treatment) neural compression after progressive thrombosis of a PED-treated dolichoectactic vertebrobasilar aneurysm. CONCLUSIONS: Treatment of unruptured aneurysms with the PED is associated with high rates of long-term angiographic occlusion and low, albeit clinically important, rates of major neurologic morbidity and mortality. Thus, flow diversion via PED placement is safe, effective, and durable.

Management strategies for pediatric patients with tectal gliomas: a systematic review.

Pediatric tectal gliomas generally have a benign clinical course with the majority of these observed radiologically. However, patients often need treatment for obstructive hydrocephalus and occasionally require cytotoxic therapy. Given the lack of level I data, there is a need to further characterize management strategies for these rare tumors. We have therefore performed the first systematic review comparing various management strategies. The literature was systematically searched from January 1, 2000, to July 30, 2020, to identify studies reporting treatment strategies for pediatric tectal gliomas. The systematic review included 355 patients from 14 studies. Abnormal ocular findings-including gaze palsies, papilledema, diplopia, and visual field changes-were a common presentation with between 13.6 and 88.9% of patients experiencing such findings. CSF diversion was the most performed procedure, occurring in 317 patients (89.3%). In individual studies, use of CSF diversion ranged from 73.1 to 100.0%. For management options, 232 patients were radiologically monitored (65.4%), 69 received resection (19.4%), 30 received radiotherapy (8.4%), and 19 received chemotherapy (5.4%). When examining frequencies within individual studies, chemotherapy ranged from 2.5 to 29.6% and radiotherapy ranged from 2.5 to 28.6%. Resection was the most variable treatment option between individual studies, ranging from 2.3 to 100.0%. Most tectal gliomas in the pediatric population can be observed through radiographic surveillance and CSF diversion. Other forms of management (i.e., chemotherapy and radiotherapy) are warranted for more aggressive tumors demonstrating radiological progression. Surgical resection should be reserved for large tumors and/or those that are refractory to other treatment modalities.

HIT in the head: a systematic review of cerebral venous sinus thrombosis in classical and autoimmune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) causes thrombosis and thrombocytopenia, usually due to prior heparin exposure, so-called classical HIT. However, in the autoimmune form, the signs and symptoms of HIT occur without prior heparin exposure. Development of cerebral venous sinus thrombosis (CVST) secondary to HIT is a rare occurrence, with relatively few reports in the literature. There is a need to better understand the clinical presentation and treatment paradigms in these rare cases. Therefore, we present the first systematic review of CVST occurring in classical and autoimmune HIT. Cases of HIT-induced CVST were identified through a systematic search of Pubmed from the date of inception to March 2021. Literature search revealed 21 cases of HIT and associated CVST with six cases (28.6%) of autoimmune HIT. Patients presented with signs and symptoms consistent with increased intracranial pressure, intracerebral hemorrhage (ICH), and/or focal neurologic deficits. Headache was the most common symptom with 12 patients (60.0%) presenting as such. 10 patients (47.6%) included in the study developed ICH. Non-heparin anticoagulants, especially direct thrombin inhibitors, were the first-line treatment for the majority of patients (55.6%). Intravenous immunoglobulin (IVIG) was used as treatment for select patients (16.7%) with autoimmune HIT. Few patients received surgical intervention for CVST (14.3%) or ICH (30.0%). Four patients had a full recovery, four patients had residual deficits, and seven patients ultimately expired. Symptoms of HIT-induced CVST are often related to CNS dysfunction. Non-heparin anticoagulants are important to treat CVST, even when patients have concomitant ICH, and may be supplemented with IVIG if treating autoimmune HIT. Rapid identification and treatment of HIT-induced CVST is imperative in order to prevent morbidity and mortality.

Thromboelastography is a Marker for Clinically Significant Progressive Hemorrhagic Injury in Severe Traumatic Brain Injury.

BACKGROUND: Coagulopathy in traumatic brain injury (TBI) is associated with increased risk of poor outcomes, but accurate prediction of clinically significant progressive hemorrhagic injury (PHI) in patients with severe TBI remains a challenge. Thromboelastography (TEG) is a real-time test of whole blood coagulation that provides dynamic information about global hemostasis. This study aimed to identify differences in TEG values between patients with severe TBI who did or did not experience clinically significant PHI. METHODS: This was a single-center retrospective cohort study of adult patients with severe TBI. Patients were eligible for inclusion if initial Glasgow coma scale (GCS) was ≤ 8 and baseline head computed tomography (CT) imaging and TEG were available. Exclusion criteria included receipt of hemostatic agents prior to TEG. PHI was defined as bleeding expansion on CT within 24 h associated with 2-point drop in GCS, neurosurgical intervention, or mortality within 24 h. The primary endpoint was TEG value differences between patients with and without PHI. Secondary endpoints included differences in conventional coagulation tests (CCTs) between groups. RESULTS: Of the 526 patients evaluated, 141 met inclusion criteria. The most common reason for exclusion was lack of baseline TEG and receipt of reversal product prior to TEG. Sixty-four patients experienced PHI in the first 24 h after presentation. K time (2.03 min vs. 1.33 min, P = 0.035) and alpha angle (65° vs. 69°, P = 0.015) were found to be significantly different in patients experiencing PHI. R time (5.25 min vs. 4.71 min), maximum amplitude (61 mm vs. 63 mm), and clot lysis at 30 min after maximum clot strength (3.5% vs. 1.7%) were not significantly different between groups. Of the CCTs, only activated partial thromboplastin time (30.3 s vs. 27.6 s, P = 0.014) was found to be different in patients with PHI. CONCLUSIONS: Prolonged K time and narrower alpha angle were found to be associated with developing clinically significant PHI in patients with severe TBI. Despite differences detected in alpha angle, median values in both groups were within normal reference ranges. These abnormalities may reflect pathologic hypoactivity of fibrinogen, and further study is warranted to evaluate TEG-guided cryoprecipitate administration in this patient population.

CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivo.

Novel combinations targeting new molecular vulnerabilities are needed to improve the outcome of patients with acute myeloid leukemia. We recently identified WEE1 kinase as a novel target in leukemias. To identify genes that are synthetically lethal with WEE1 inhibition, we performed a short interfering RNA screen directed against cell cycle and DNA repair genes during concurrent treatment with the WEE1 inhibitor MK1775. CHK1 and ATR, genes encoding two replication checkpoint kinases, were among the genes whose silencing enhanced the effects of WEE1 inhibition most, whereas CDK2 short interfering RNA antagonized MK1775 effects. Building on this observation, we examined the impact of combining MK1775 with selective small molecule inhibitors of CHK1, ATR and cyclin-dependent kinases. The CHK1 inhibitor MK8776 sensitized acute myeloid leukemia cell lines and primary leukemia specimens to MK1775 ex vivo, whereas smaller effects were observed with the MK1775/MK8776 combination in normal myeloid progenitors. The ATR inhibitor VE-821 likewise enhanced the antiproliferative effects of MK1775, whereas the cyclin-dependent kinase inhibitor roscovitine antagonized MK1775. Further studies showed that MK8776 enhanced MK1775-mediated activation of the ATR/CHK1 pathway in acute leukemia cell lines and ex vivo. These results indicate that combined cell cycle checkpoint interference with MK1775/MK8776 warrants further investigation as a potential treatment for acute myeloid leukemia.

Nonsteroidal Anti-inflammatory Medications in Cranial Neurosurgery: Balancing Opioid-Sparing Analgesia with Bleeding Risk.

Postcraniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of postcraniotomy patients, as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Nonsteroidal anti-inflammatory drugs (NSAIDs) present as a potential solution due to their nonaddictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. The degree to which NSAIDs alter platelet function and bleeding time to a clinically relevant manner has remained controversial, although several well-designed studies concluded that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for postintracranial neurosurgical procedure pain management.

Neuromodulation: What the neurointerventionalist needs to know.

Neuromodulation is the alteration of neural activity in the central, peripheral, or autonomic nervous systems. Consequently, this term lends itself to a variety of organ systems including but not limited to the cardiac, nervous, and even gastrointestinal systems. In this review, we provide a primer on neuromodulation, examining the various technological systems employed and neurological disorders targeted with this technology. Ultimately, we undergo a historical analysis of the field's development, pivotal discoveries and inventions gearing this review to neuro-adjacent subspecialties with a specific focus on neurointerventionalists.

National Institutes of Health grant funding for cerebrovascular diseases.

BACKGROUND: Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types. OBJECTIVE: To examine the current scope of NIH grant funding for cerebrovascular conditions. METHODS: The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses. RESULTS: We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546). CONCLUSION: Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS.

Triple Aspiration Versus Conventional Aspiration Techniques: A Randomized In-Vitro Evaluation.

BACKGROUND AND PURPOSE: A single aspiration maneuver using a large volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes has been proposed as a means to improve efficacy over single aspiration. In this study, we sought to investigate the efficacy of a "triple aspiration technique" where a large volume syringe is cycled three times prior to catheter retraction during aspiration thrombectomy. MATERIALS AND METHODS: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of three different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final mTICI 2c/3), the number of thrombectomy attempts to achieve mTICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-micron cell strainer placed at the outflow of the model and quantified using an image processing algorithm. The vacuum pressures were measured using a pressure transducer (Honeywell, NC, USA). RESULTS: A total of 102 replicates were performed, 34 for each technique. The triple aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% vs. 41.1%, p= 0.02). Additionally, the triple aspiration technique achieved complete clot removal with a significantly lower number of thrombectomy attempts compared to single syringe aspiration (1.2 ± 0.5 vs. 1.8 ± 0.8, p=0.005). The triple aspiration technique generated significantly higher vacuum pressure than both the single syringe and vacuum pump aspiration (28.3 ± 0.2 vs. 27.2 ± 0.3 (p= 0.002) and 26.2 ± 0.4 (p=0.001), respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups. CONCLUSIONS: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting. ABBREVIATIONS: AcommA = anterior communicating artery; FPE = first pass efficacy; ICA = internal carotid artery; MCA = middle cerebral artery; MT = mechanical thrombectomy; mTICI = modified thrombolysis in cerebral infarction scale; PcommA = posterior communicating artery.

Safety of the immediate use of nonsteroidal anti-inflammatory drugs after adult craniotomy for tumor.

OBJECTIVE: Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS: The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS: Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33-29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54-3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS: Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

Weathering the storm: a single-institution experience with paroxysmal sympathetic hyperactivity after brain tumor resection in pediatric patients.

OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) is a complication of severe traumatic or hypoxic brain injury characterized by transient episodes of tachycardia, tachypnea, hypertension, hyperthermia, diaphoresis, and/or dystonic posturing. Posttraumatic "sympathetic storms" are associated with poor outcomes. PSH rarely occurs after brain tumor resection in pediatric patients; only 4 cases have been published since 1929. Thus, the authors sought to report their experience with postcraniotomy PSH in pediatric brain tumor patients. METHODS: A retrospective study of patients younger than 18 years of age who underwent craniotomy for brain tumor resection at a single center by a single surgeon over a 7-year period was performed. A clinical diagnosis of postoperative PSH was recorded. Recorded outcomes included the interval between surgery and initiation of cytotoxic therapy, need for long-term CSF diversion, length of hospital stay, and survival. RESULTS: Of the 150 patients who were included for analysis, 4 patients were diagnosed with postoperative PSH for an overall occurrence of 2.7%. PSH patients were younger than non-PSH patients (1.8 ± 0.4 years vs 9.2 ± 5.3 years, p = 0.010) and tended to have intraventricular tumors close to the thalamus, basal ganglia, and/or brainstem. PSH patients experienced longer hospital admissions (44.3 ± 23.4 days vs 6.8 ± 9.4 days, p = 0.001), a shorter interval between surgery and initiation of cytotoxic cancer-directed therapy (14.3 ± 8.0 days vs 90.7 days ± 232.9 days, p = 0.011), and increased need for long-term CSF diversion compared with non-PSH patients (75% vs 25%, p = 0.005). At the last follow-up, 50% of PSH patients had died compared with 13% of non-PSH patients (p = 0.094). CONCLUSIONS: PSH is a rare postoperative complication that may affect young children with periventricular tumors and is associated with poorer clinical outcomes. Increasing awareness of this condition is vital to improving patient outcomes.

Percutaneous transorbital transvenous embolization of a cavernous sinus dural arteriovenous fistula via the superior orbital fissure-technical video.

Carotid-cavernous dural arteriovenous fistulas causing debilitating ocular symptoms and/or retrograde cortical venous drainage necessitate curative treatment, which is achieved by disrupting the proximal draining vein. Transvenous embolization of carotid-cavernous dural arteriovenous fistulas can be achieved through the superior or inferior petrosal sinuses, facial veins, or superior ophthalmic veins.1, 2 However, if these approaches are not feasible, various percutaneous approaches have been described that use the skull base foramina to provide direct access to the cavernous sinus.3, 4 Here we present the case of a 54-year-old male with carotid-cavernous dural arteriovenous fistulas with cortical venous drainage causing diplopia that was cured using a percutaneous transorbital approach. We discuss the alternative endovascular strategies for treating carotid-cavernous dural arteriovenous fistulas and why they were not chosen, the technical nuances of the transorbital approach as well as the pearls and pitfalls of this seldom used technique. A comprehensive understanding of the many approaches for treating carotid-cavernous dural arteriovenous fistulas is important for neurointerventionalists.

Above-The-Hairline Suboccipital Transverse Approach for the Treatment of Chiari I Malformation.

BACKGROUND: Chiari I malformation is a common pediatric neurosurgical disorder with an established treatment paradigm. Posterior fossa decompression and duraplasty (PFDD) is associated with symptom improvement but it carries postoperative risk, particularly cerebrospinal fluid (CSF) leak and wound complications. In addition, the cosmetic outcomes of PFDD have been overlooked in the literature. OBJECTIVE: To describe a novel approach for PFDD in which the transverse surgical incision is completely hidden above the hairline and to report early outcomes in a prospective patient cohort. METHODS: Clinical and cosmetic outcomes were recorded for 15 consecutive pediatric patients who underwent PFDD for Chiari I malformation via the above-the-hairline transverse suboccipital approach. RESULTS: The median clinical follow-up time was 6 months (range 1-12 months), and the majority of patients experienced significant improvement of their preoperative symptoms. Three patients (20%) experienced complications associated with surgery, which included injury to the greater occipital nerve, CSF hypotension and subfascial pseudomeningocele, and superficial wound dehiscence that resolved spontaneously with oral antibiotics. Zero patients (0%) returned to the operating room for persistent CSF leak, deep wound infection, or revision decompression. An excellent cosmetic outcome was achieved in 12 patients (80%). No patient had a poor cosmetic outcome. CONCLUSION: The above-the-hairline transverse suboccipital approach for PFDD in patients with Chiari I malformation offers favorable cosmetic outcomes and fascial closure while permitting adequate decompression.

Stereotactic radiosurgery for intermediate- and high-grade arteriovenous malformations: outcomes stratified by the supplemented Spetzler-Martin grading system.

OBJECTIVE: The supplemented Spetzler-Martin (Supp-SM) grading system was developed to improve the predictive accuracy of surgical risk for patients with brain arteriovenous malformations (AVMs). The aim of this study was to apply the Supp-SM grading system to patients having stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) intermediate- (grade III) or high-grade (grade IV-V) AVMs to enable comparison with published microsurgical series. METHODS: In 219 patients who underwent SRS during the period from 1990 to 2016, the Supp-SM grade was calculated for SM grade III (n = 154) or SM grade IV-V (n = 65) AVMs. The Supp-SM grades in these patients were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). Sixty patients (27%) had deep AVMs (basal ganglia, thalamus, or brainstem). Thirty-nine patients (18%) had volume-staged SRS; 41 patients (19%) underwent repeat SRS. The median follow-up period was 69 months for SM grade III AVMs and 113 months for SM grade IV-V AVMs. RESULTS: AVM obliteration was confirmed in 163 patients (74%) at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. Thirty-one patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). Six patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurological decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of nonobliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurological decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading score did not correlate with either obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurological decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38). CONCLUSIONS: The Supp-SM grading system was not predictive of outcomes after SRS of intermediate- or high-grade AVM. In a cohort that included a high percentage (47%) of "inoperable" AVMs according to Supp-SM grade (≥ 7), most patients had obliteration after SRS, although there was a high risk of neurological decline.

Predicting disease progression and the need for tumor-directed treatment in tectal plate gliomas.

OBJECTIVE: Tectal plate gliomas are rare, slow-growing tumors of the midbrain that are discovered predominantly in the pediatric population. Because of their indolent nature, treatment mainly consists of observation and management of hydrocephalus. Unfortunately, a subset of tectal gliomas may exhibit tumor enlargement and disease progression. Currently, there are no established guidelines for predicting future progression of tectal gliomas or the need for tumor-directed treatment. In this paper, the authors present a large case series of tectal plate gliomas with the aim of determining early indicators of tumor progression and the need for tumor-directed treatment in a pediatric population, along with providing their experience in treating progressive tumors. METHODS: A retrospective chart review of 170 patients diagnosed with tectal plate glioma from a single institution, of whom 67 were pediatric patients (≤ 18 years of age), was performed. Univariate analysis was used to determine statistically significant predictors of symptomatic disease progression requiring eventual tumor-directed therapy. RESULTS: The median patient age of the full cohort was 24 years (range 0-73 years). Compared with the pediatric population, the adult population had more instances of incidental lesions (p < 0.001) and lower rates of hydrocephalus (50% vs 84%, p < 0.001). Of the pediatric patients who had ≥ 5 years of follow-up (n = 51), 12 (24%) experienced radiological progression and 13 (25%) required treatment for their tumor. The 1-year, 5-year, and 10-year radiographic progression-free survival (PFS) rates were 98%, 90%, and 86%, respectively. In univariate analysis, lesion involvement of the pons, moderate T1 hypointensity, and moderate contrast enhancement on baseline radiology were significantly associated with worse radiographic PFS. Alternatively, significant predictors of requiring tumor-directed treatment included extraocular eye movement abnormalities at presentation, involvement of the lesion beyond the tectum on baseline radiology, moderate T1 hypointensity, moderate contrast enhancement, and an increase in total lesion size during progression. At the most recent follow-up, 94% of the patients had stable/nonprogressive disease, 2% had progressive disease, and 4% died of tumor progression. CONCLUSIONS: Patients who demonstrate radiographic progression may not necessarily experience clinical/symptomatic progression or require tumor-directed treatment. Certain patient presentation characteristics and baseline radiographic features may be predictive of worse radiographic PFS or the need for future tumor-directed treatment in the pediatric population. Typically, the natural history of these lesions lends to excellent long-term survival, even in patients who experience clinical progression, should appropriate treatment be initiated.

Iatrogenic vertebral artery injury with concomitant contralateral idiopathic vertebral artery dissection managed with intravascular intervention: a case report.

Background: Vertebral artery injury (VAI) is a known potential complication of posterior cervical fusion surgery. Pre-operative imaging is used to determine the patency of bilateral vertebral arteries during the planning and execution of surgery. This case illustrates an example of a staged anterior/posterior cervical reconstruction in which an iatrogenic VAI combined with a contralateral idiopathic vertebral artery dissection not identified on pre-operative imaging resulted in absent basilar artery anterograde flow. Case Description: A 61-year-old female underwent planned staged anterior cervical decompression C4-T1 with posterior cervical fusion C2-T4 for the treatment of degenerative cervical myeloradiculopathy. During the second stage posterior fusion, iatrogenic VAI occurred during drilling for placement of the right C2 pars screw. Upon post-operative angiography, in addition to the known right VAI, there was a new left vertebral artery dissection that occurred during/after the anterior stage. The basilar artery was only filled in retrograde fashion from the right internal carotid artery across the right posterior communicating artery. The left vertebral artery dissection was treated with telescoping flow diverting stents to restore flow to the basilar artery and the right VAI was treated with coiling. Conclusions: Surgeons should be aware of the possibility, while rare, that an occult injury to the non-injured artery is always a possibility if significant deformity correction or alignment change has occurred during cervical spine surgery. Working closely with neurointerventional colleagues can be invaluable to quickly assess and if necessary, restore blood flow to the brain through these life saving techniques.