Association of socioeconomic status with the management outcome of unruptured intracranial arteriovenous malformation.

OBJECTIVE: The longitudinal management of unruptured brain arteriovenous malformation (bAVM) is crucial. To date, no study in the United States has evaluated the impact of socioeconomic status (SES) on bAVM outcome. Herein, the authors aimed to clarify the impact of SES, as indicated by the area deprivation index (ADI), on bAVM outcome. METHODS: A retrospective analysis of an institutional bAVM database was conducted. Non-hereditary hemorrhagic telangiectasia patients with a single unruptured bAVM in the period from 1990 to 2021 were included in the analysis. The ADI was categorized as low (ADI ≤ 15th percentile), mid (15th percentile < ADI < 85th percentile), and high (ADI ≥ 85th percentile), with a low ADI indicating the most advantaged group. Patient baseline and follow-up data were analyzed. The primary outcome of interest was nonindependence (modified Rankin Scale [mRS] score > 2) at the last follow-up. A multivariable logistic regression model was performed. RESULTS: A total of 589 patients with unruptured bAVMs were included in the study. The mean patient age at diagnosis was 37.2 years, and 283 patients (48.0%) were male. Of the bAVMs, 238 (40.4%) had a low Spetzler-Martin grade (SMG < III), 194 (32.9%) had a moderate grade (SMG III), and 157 (26.7%) had a high grade (SMG > III). Sixty-nine patients (11.7%) were in the low-ADI group, 476 (80.8%) in the mid-ADI group, and 44 (7.5%) in high-ADI group. Increasing age (OR 1.02, 95% CI 1.01-1.04, p < 0.001), poor baseline mRS score (OR 3.27, 95% CI 1.32-7.88, p = 0.008), treatment with surgery plus radiosurgery with or without embolization (OR 3.21, 95% CI 1.03-9.81, p = 0.041), mid SMG (OR 1.94, 95% CI 1.11-3.44, p = 0.021), high SMG (OR 2.08, 95% CI 1.13-3.88, p = 0.020), longer follow-up (OR 1.05, 95% CI 1.03-1.08, p < 0.001), and mid ADI (OR 3.08, 95% CI 1.34-8.39, p = 0.015) were significantly associated with a poor outcome. A high ADI tended toward a poor outcome (OR 2.93, 95% CI 0.92-9.88, p = 0.071). Eventual obliteration of a bAVM was the only protective predictor of poor outcome (OR 0.55, 95% CI 0.30-0.98, p = 0.046). CONCLUSIONS: This study revealed that relatively disadvantaged patients with unruptured bAVMs are more likely to experience nonindependent outcomes at the last follow-up, after adjusting for confounding variables. An emphasis on social support may be beneficial for patients with a lower SES.

The Natural History of Hemorrhage in Brain Arteriovenous Malformations-Poisson Regression Analysis of 1066 Patients in a Single Institution.

BACKGROUND AND OBJECTIVES: Natural history of hemorrhage in brain arteriovenous malformations (bAVM) is reported at 2%-4% per year. Published studies using survival analysis fail to account for recurrent hemorrhagic events. In this study, we present a large, single institution series to elucidate the natural history of bAVM using multivariable Poisson regression. METHODS: This is a retrospective cohort study. All patients with bAVM seen at our institution from 1990 to 2021 were included. Hemorrhages after detection of bAVM during the untreated interval were recorded. Natural history of hemorrhage was calculated by dividing number of hemorrhages by untreated interval. The frequency of hemorrhages followed a Poisson distribution. Multivariable Poisson regression with an offset variable of untreated interval in patient-years was constructed. Model selection was through a stepwise Akaike information criterion method. Stratified hemorrhagic rate was presented using different combinations of significant factors. RESULTS: A total of 1066 patients with nonhereditary hemorrhagic telangiectasia harboring a single bAVM were included. Ninety (8.44%) patients had 101 hemorrhages during an untreated interval of 3596.3344 patient-years, translating to an overall hemorrhagic rate of 2.81% per year. Significant factors increasing hemorrhage risk included ruptured presentation ( P < .001), increasing age ( P < .001), female sex ( P = .043), and deep location ( P = .040). Adult male patients with ruptured presentation and deep bAVMs sustained the highest annual risk at 10.81%, whereas no hemorrhages occurred in unruptured pediatric male patients or ruptured pediatric (younger than 18 years) male patients with superficial bAVMs. CONCLUSION: Hemorrhage after bAVM detection occurs in 8.41% of all patients, and the rate averages 2.81% per year. However, this risk varies from 0.00% to 10.81% per year depending on various risk factor combinations. Efforts should be made to stratify bAVM hemorrhage rate by risk factors for more precise estimation of bleeding risk if left untreated.

Cost-Effectiveness of a Direct-Aspiration First-Pass Technique versus Stent Retriever in Mechanical Thrombectomy.

OBJECTIVE: A direct-aspiration first-pass technique (ADAPT) in mechanical thrombectomy has been described in recent studies as an efficacious strategy compared with using a stent retriever (SR). We sought to evaluate for cost differences of ADAPT technique versus SR as an initial approach. METHODS: We conducted a retrospective analysis of consecutive patients with mechanical thrombectomy at our institution between 2022 and 2023. Patients were grouped into ADAPT with/without SR as a rescue strategy and SR as an initial approach with allowance of concomitant aspiration. Direct cost data (consumables) were obtained. Baseline demographics, stroke metrics, procedure outcomes and cost, and last follow-up outcomes in modified Rankin Scale were compared between 2 groups. RESULTS: Fifty-six patients were included. Thirty-seven (66.1%) underwent ADAPT, with 11 (29.7%) eventually requiring an SR. Mean age was 64.8 years. The average National Institutes of Health Stroke Scale score was 13.2 in the ADAPT group and 14.0 in the SR group (P = 0.68), with a similar proportion of tissue plasminogen activator (P = 0.53), site of occlusion (P = 0.66), and tandem occlusion (P = 0.69) between the groups. Recanalization was achieved in 94.6% of all patients, with an average of 1.9 passes, 89.3% being TICI 2B or above, with no differences between the 2 groups. Significantly lower cost (P < 0.01) was observed in ADAPT ($14,243.4) compared with SR ($19,003.6). Average follow-up duration was 180.2 days, with mortality of 23.2%. At last follow-up, 55.4% remained functionally independent (modified Rankin Scale score <3) with no difference (P = 0.56) between the ADAPT (59.5%) and SR (47.4%) groups. CONCLUSIONS: Outcomes were comparable between the ADAPT and SR groups. ADAPT reduced procedural consumables cost by approximately $5000 (25%), even if stent retrievers were allowed to be used for rescue. Establishing ADPAT as initial approach may bring significant direct cost savings while obtaining similar outcomes.

Absence of Ischemic Injury after Sacrificing the Superior Petrosal Vein during Microvascular Decompression.

BACKGROUND: Sacrificing the superior petrosal vein (SPV) is controversial during a microvascular decompression (MVD). There have been multiple reports of complications including life-threatening brainstem infarction and cerebellar edema. OBJECTIVE: To analyze the potential for vascular complications when the SPV is sacrificed during an MVD. METHODS: Retrospective chart review was performed to identify all MVDs for trigeminal neuralgia and hemifacial spasm from 2007 to 2018 at 1 institution. Cases with ≥1 mo of follow-up were included and SPV sacrifice was noted. The primary outcome was complications related to SPV sacrifice including sinus thrombosis, cerebellar edema, and midbrain or pontine infarction. Imaging was used to confirm all potential vascular complications noted in medical records. Fisher's exact test and unpaired t-tests were used to compare between groups. RESULTS: A total of 732 MVD cases were identified and 592 met inclusion criteria with an average follow-up of 11.8 ± 16.4 mo and a male-to-female ratio of 1:2.2. The SPV was sacrificed in 217 cases and retained in 375 cases. No SPV-related vascular complications were found in this study. Two unrelated cases of vascular complications were identified and both were in the nonsacrificed group. One case involved cerebellar bleeding while the other was an ipsilateral transverse sinus thrombosis that was present preoperatively. CONCLUSION: In MVDs, there is no difference in the rate of vascular complications when the SPV is sacrificed compared to preserved. To best visualize a cranial nerve and optimize safe decompression, surgeons should feel free to sacrifice the SPV.

Retrosigmoid approach for glycerin rhizotomy in the treatment of trigeminal neuralgia without overt arterial compression: updated case series.

OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain disorder characterized by severe, lancinating facial pain that is commonly treated with neuropathic medication, percutaneous rhizotomy, and/or microvascular decompression (MVD). Patients who are not found to have distinct arterial compression during MVD present a management challenge. In 2013, the authors reported on a small case series of such patients in whom glycerin was injected intraoperatively into the cisternal segment of the trigeminal nerve. The objective of the authors' present study was to report their updated experience with this technique to further validate this novel approach. METHODS: The authors performed a retrospective analysis of data obtained in patients in whom glycerin was directly injected into the inferior third of the cisternal portion of the trigeminal nerve. Seventy-four patients, including 14 patients from the authors' prior study, were identified, and demographic information, intraoperative findings, postoperative course, and complications were recorded. Fisher's exact test, unpaired t-tests, and Kaplan-Meier survival curves using Mantel log-rank test were used to compare the 74 patients with a cohort of 476 patients who received standard MVD by the same surgeon. RESULTS: The 74 patients who underwent MVD and glycerin injection had an average follow-up of 19.1 ± 18.0 months, and the male/female ratio was 1:2.9. In 33 patients (44.6%), a previous intervention for TN had failed. On average, patients had an improvement in the Barrow Neurological Institute Pain Intensity score from 4.1 ± 0.4 before surgery to 2.1 ± 1.2 after surgery. Pain improvement after the surgery was documented in 95.9% of patients. Thirteen patients (17.6%) developed burning pain following surgery. Five patients developed complications (6.7%), including incisional infection, facial palsy, CSF leak, and hearing deficit, all of which were minor. CONCLUSIONS: Intraoperative injection of glycerin into the trigeminal nerve is a generally safe and potentially effective treatment for TN when no distinct site of arterial compression is identified during surgery or when decompression of the nerve is deemed to be inadequate.

The Effect of Flow-Related Aneurysms on Hemorrhagic Risk of Intracranial Arteriovenous Malformations.

BACKGROUND: Previous reports indicated an association between hemorrhagic presentation and flow-related aneurysms in arteriovenous malformation (AVM) patients. However, it remains unclear whether these flow-related aneurysms result in the hemorrhage of AVM. OBJECTIVE: To characterize this hemorrhage risk using our institutional experience over 25 yr. METHODS: We retrospectively reviewed records of patients at our institution diagnosed with AVM from 1990 to 2015. Patients without associated aneurysms (AVM only) and those with flow-related aneurysms (AVM-FA) were compared. Those with intranidal or unrelated aneurysms were excluded. Annual risk of AVM-related hemorrhage was calculated using the birth-to-treatment approach and compared using Poisson rate ratio test. RESULTS: Among 526 patients, there were 457 AVM only patients and 69 with flow-related aneurysms. AVM-FA patients were older (P = .005). AVMs with flow-related aneurysms were more likely located in the cerebellar vermis and hemispheres (P = .023 and .001, respectively). Presence of flow-related aneurysms increased the risk of presentation with subarachnoid hemorrhage (P < .001). Interestingly, no significant differences in presenting hemorrhage due to AVM rupture were found (P > .356). The majority of aneurysms were untreated (69.5%), and only 8 (9.8%) had ruptured presentation. At follow-up (mean = 5.3 yr), patients with flow-related aneurysms were less likely to develop seizures (P = .004). The annual risk of AVM hemorrhage was 1.33% and 1.05% for AVM only patients and AVM-FA patients, respectively (P = .248). CONCLUSION: Despite increased risk of subarachnoid hemorrhage at presentation, there was no increased likelihood of rupture in AVMs with flow-related aneurysms. More studies are warranted, as clarifying the competing risks of AVM vs aneurysm rupture may be critical in determining optimal treatment strategy.

Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system.

Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic factors, such as iatrogenic immunosuppression caused by conventional therapies, impact the efficacy of anti-PD-1 therapy are paramount. Given the widespread use of corticosteroids in cancer management and their immunosuppressive nature, this study sought to determine how corticosteroids influence anti-PD-1 responses and whether their effects were dependent on tumor location within the periphery versus central nervous system (CNS), which may have a more limiting immune environment. In well-established anti-PD-1-responsive murine tumor models, corticosteroid therapy resulted in systemic immune effects, including severe and persistent reductions in peripheral CD4+ and CD8 + T cells. Corticosteroid treatment was found to diminish the efficacy of anti-PD-1 therapy in mice bearing peripheral tumors with responses correlating with peripheral CD8/Treg ratio changes. In contrast, in mice bearing intracranial tumors, corticosteroids did not abrogate the benefits conferred by anti-PD-1 therapy. Despite systemic immune changes, anti-PD-1-mediated antitumor immune responses remained intact during corticosteroid treatment in mice bearing intracranial tumors. These findings suggest that anti-PD-1 responses may be differentially impacted by concomitant corticosteroid use depending on tumor location within or outside the CNS. As an immune-specialized site, the CNS may potentially play a protective role against the immunosuppressive effects of corticosteroids, thus sustaining antitumor immune responses mediated by PD-1 blockade.

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM.

The use of inhibitory checkpoint blockade in the management of glioblastoma has been studied in both preclinical and clinical settings. TIGIT is a novel checkpoint inhibitor recently discovered to play a role in cancer immunity. In this study, we sought to determine the effect of anti-PD-1 and anti-TIGIT combination therapy on survival in a murine glioblastoma (GBM) model, and to elucidate the underlying immune mechanisms. Using mice with intracranial GL261-luc+ tumors, we found that TIGIT expression was upregulated on CD8+ and regulatory T cells (Tregs) in the brain compared to draining cervical lymph nodes (CLN) and spleen. We then demonstrated that treatment using anti-PD-1 and anti-TIGIT dual therapy significantly improved survival compared to control and monotherapy groups. The therapeutic effect was correlated with both increased effector T cell function and downregulation of suppressive Tregs and tumor-infiltrating dendritic cells (TIDCs). Clinically, TIGIT expression on tumor-infiltrating lymphocytes was shown to be elevated in patient GBM samples, suggesting that the TIGIT pathway may be a valuable therapeutic target. Expression of the TIGIT ligand, PVR, further portended a poor survival outcome in patients with low-grade glioma. We conclude that anti-TIGIT is an effective treatment strategy against murine GBM when used in combination with anti-PD-1, improving overall survival via modifications of both the T cell and myeloid compartments. Given evidence of PVR expression on human GBM cells, TIGIT presents as a promising immune therapeutic target in the management of these patients.

Ventricular Volume Dynamics During the Development of Adult Chronic Communicating Hydrocephalus in a Rodent Model.

INTRODUCTION: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood. OBJECTIVE: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms. METHODS: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings. RESULTS: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013). CONCLUSIONS: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended.

Comparison of Hemorrhagic Risk in Intracranial Arteriovenous Malformations Between Conservative Management and Embolization as the Single Treatment Modality.

BACKGROUND: Embolization has been discussed as a feasible single modality treatment for intracranial arteriovenous malformations (AVMs). OBJECTIVE: To compare hemorrhagic risk between embolization and conservative management in a multivariate survival analysis. METHODS: We retrospectively reviewed records of patients with intracranial AVMs evaluated at our institution from 1990 to 2013. We included patients recommended to undergo embolization without other treatment modalities and patients managed conservatively. Multivariate Cox regression analysis of hemorrhage-free survival was performed, with the survival interval right-censored to date of either last follow-up or salvage treatment. RESULTS: We identified 205 patients matching our inclusion criteria, with 160 patients in the noninterventional group and 45 in the embolization group. The average age of all patients was 40.2 ± 19.5 yr, with younger patients undergoing embolization more often (P = .026). Fifty-one (31.9%) conservatively managed patients and 13 (28.9%) patients treated by embolization (P = .703) presented with hemorrhage. Other baseline characteristics were similar between the 2 management groups. During an average follow-up period of 7.7 yr, 30 patients (14.6%) experienced hemorrhage recurrence. Multivariate Cox regression revealed older age (P = .031) and hemorrhagic presentation (P < .001) to be statistically associated with follow-up hemorrhage. In a subset analysis of unruptured AVMs, embolization was associated with a 4-fold hazard ratio of hemorrhage compared to conservative management (P = .044). CONCLUSION: Older age and initial presentation with hemorrhage were associated with increased risk of hemorrhage during follow-up. Treatment of AVMs with embolization as the sole modality may increase hemorrhagic risk compared with conservative management, especially in unruptured AVMs.

Risk Assessment of Hemorrhage of Posterior Inferior Cerebellar Artery Aneurysms in Posterior Fossa Arteriovenous Malformations.

BACKGROUND: Posterior fossa arteriovenous malformations (AVMs) are associated with increased risk of rupture and severe consequences from such rupture. The hemorrhagic risk of prenidal aneurysms (anr) on the posterior inferior cerebellar artery (PICA) may exceed that of the AVM in posterior fossa AVMs fed by PICA (PICA-AVM). OBJECTIVE: To characterize the relative risks of aneurysm and AVM hemorrhage in patients with posterior fossa AVMs. METHODS: We retrospectively reviewed patients diagnosed with AVM. Patients with posterior fossa AVMs were divided into 3 groups: PICA-AVM with prenidal aneurysm (PICA-AVM-anr group), PICA-AVM without prenidal aneurysm (PICA-AVM group), and AVMs without PICA feeder with/without aneurysm (AVM-only group). Patient and lesion characteristics and treatment outcomes were compared. ANOVA and chi squared tests were used for statistical analyses. RESULTS: Our cohort included 85 patients. Mean age was 45.3 ± 18.1 yr, with 43(50.6%) female patients. Fifty-one patients (60.0%) had hemorrhagic presentation, and 27 (31.8%) experienced acute hydrocephalus. Patients in the PICA-AVM-anr group (n = 11) were more likely to present with aneurysmal subarachnoid hemorrhage (SAH; P = .005) and less likely to have AVM rupture (P < .001). Ten (90.9%) patients presented with hemorrhage, 6 (60.0%) of which resulted from aneurysm rupture. Of these 6, 5 (83.3%) had acute hydrocephalus. No patients with AVM rupture had hydrocephalus. Eight (72.7%) received aneurysm treatment prior to AVM treatment. There were no significant differences in post-treatment outcomes dependent on treatment order. CONCLUSION: In addition to relatively higher risk of AVM rupture from infratentorial location and prenidal aneurysm, a higher risk of aneurysm rupture rather than AVM rupture was observed in patients with PICA-AVM-anr complex.

Targeting cytokines for treatment of neuropathic pain.

BACKGROUND: Neuropathic pain is a challenging condition often refractory to existing therapies. An increasing number of studies have indicated that the immune system plays a crucial role in the mediation of neuropathic pain. Exploration of the various functions of individual cytokines in neuropathic pain will provide greater insight into the mechanisms of neuropathic pain and suggest potential opportunities to expand the repertoire of treatment options. METHODS: A literature review was performed to assess the role of pro-inflammatory and anti-inflammatory cytokines in the development of neuropathic pain. Both direct and indirect therapeutic approaches that target various cytokines for pain were reviewed. The current understanding based on preclinical and clinical studies is summarized. RESULTS AND CONCLUSIONS: In both human and animal studies, neuropathic pain has been associated with a pro-inflammatory state. Analgesic therapies involving direct manipulation of various cytokines and indirect methods to alter the balance of the immune system have been explored, although there have been few large-scale clinical trials evaluating the efficacy of immune modulators in the treatment of neuropathic pain. TNF-α is perhaps the widely studied pro-inflammatory cytokine in the context of neuropathic pain, but other pro-inflammatory (IL-1ß, IL-6, and IL-17) and anti-inflammatory (IL-4, IL-10, TGF-ß) signaling molecules are garnering increased interest. With better appreciation and understanding of the interaction between the immune system and neuropathic pain, novel therapies may be developed to target this condition.

Male Gender Associated with Post-Treatment Seizure Risk of Pediatric Arteriovenous Malformation Patients.

BACKGROUND: Seizure risk has not been fully characterized in pediatric patients with arteriovenous malformations (AVMs). OBJECTIVE: To describe the progression and risk factors of post-treatment seizure in children with AVMs. METHODS: We retrospectively reviewed pediatric patients diagnosed with intracranial AVMs at our institution between 1990 and 2013. Clinical and angiographic variables were included in univariate and multivariate Cox proportional hazard models to explore risk factors associated with time-related seizure outcomes. The outcome event is defined as first seizure occurrence after initial treatment. Kaplan-Meier survival curve is depicted for each significant variable, and survival differences were confirmed by Log-rank test. RESULTS: We included 90 pediatric patients with complete data in our study cohort. Average age is 13.3 ± 3.8 years with 43.3% male patients. Thirty-seven patients had a hemorrhagic presentation, and 39 patients presented with seizure. Post-treatment seizure occurred in 33 patients (36.7%) over an average follow-up period of 8.1 ± 10.6 years; average time to onset is 5.3 ± 8.2 years, with partial seizures as the most common presentation. Multivariate Cox proportional hazard regression revealed seizure presentation ( P = .005), male gender ( P = .026), and nonconservative treatment modality to be significantly associated with earlier onset of post-treatment seizure after adjusting for AVM location and deep venous drainage. Overall annualized seizure risk is 7.4% for patients with pretreatment seizure, and 1.4% for those without. CONCLUSION: Risk of seizure persists after treatment in pediatric AVM patients. Seizure presentation, male gender, and nonconservative management are associated with increased risk of post-treatment seizure. Early identification of these risk factors provides important information for determining seizure management strategies.

Ventriculoatrial versus ventriculoperitoneal shunt complications in idiopathic normal pressure hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a devastating condition that affects the elderly population. Although ventriculoatrial (VA) shunts can be used to manage iNPH, concerns for associated cardiopulmonary and renal complications have decreased their use. However, the rate of these complications is not well understood within this population of patients. PATIENTS AND METHODS: A retrospective review of the electronic medical records of patients diagnosed with iNPH by the senior author between 1993 and 2015 was performed. Demographic information and baseline symptoms were assessed. Complications including infection, shunt obstruction, overdrainage, cardiopulmonary events, renal dysfunction, and shunt revision were recorded. Complication rates were compared between VA and VP shunted patients. Statistical analysis using Chi-square test, Fisher's exact test, logistic regression, Wald t-test, Poisson regression, ANOVA, and ANCOVA was performed. RESULTS: 496 Patients, including 150 receiving VA shunts and 346 receiving VP shunts, were included in the study. The median age was 74 and 73 for VA and VP shunted patients, respectively, with slight male predominance in both (58.0% and 58.4% for VA and VP groups, respectively). A total of 36.0% of VA shunted patients and 42.5% of VP shunted patients experienced at least one post-operative complication. Overdrainage was the most commonly experienced complication in both VA (27.4%) and VP patients (19.9%). Infection occurred in only 2.0% of patients, and renal complications occurred in 1.3%. No patients had cardiopulmonary complications. VA shunted patients were significantly less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients (p=0.008 and <0.001, respectively). Only dizziness and gait disturbance at baseline were correlated with a shorter time to revision in VA shunted patients (p=0.002 for both). CONCLUSION: Although cardiopulmonary and renal complications are serious concerns associated with VA shunt placement, they were uncommon in patients with iNPH. VA shunted patients were less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients. Therefore, VA shunts should be considered as an alternative primary treatment option in the iNPH population.

Differences in Functional Outcome Across Subtypes with Spetzler-Martin Grade II Arteriovenous Malformations.

BACKGROUND: The Spetzler-Martin grading system for brain arteriovenous malformations (AVMs) is based on size (S), eloquence (E), and deep venous drainage (V). However, variation exists due to subgroup heterogeneity. While previous studies have demonstrated variations in outcomes within grade III AVMs, no studies have focused on grade II AVM subtypes. OBJECTIVE: We aim to delineate how functional outcomes differ among patients with subtypes of grade II AVMs. METHODS: We retrospectively reviewed patients with AVMs evaluated at our institution from 1990 to 2013. Grade II AVMs were divided into 3 subtypes: group 1 (S2V0E0), group 2 (S1V0E1), and group 3 (S1V1E0). Baseline characteristics were compared, and functional status was assessed using the modified Rankin Scale (mRS) at pretreatment and last follow-up. Differences in mRS between the 2 time points were compared. RESULTS: A total of 208 grade II patients (34.0%) were retrieved from 611 graded patients. After accounting for missing data, our cohort consisted of 137 patients. Mean age of all patients was 37.2 years, with 74 females (54.0%). No significant difference was observed across subgroups for pretreatment mRS ( P = .096), treatment modalities ( P = .943), follow-up durations ( P = .125), and mRS at last follow-up ( P = .716). In a subgroup analysis between group 1 and group 3, more patients with worsened mRS were observed in group 3 ( P = .039). This distinction was further confirmed in surgically treated patients ( P = .049), but not in patients treated with radiosurgery ( P = .863). CONCLUSION: Subtypes of grade II AVMs portend different posttreatment gains in functional outcome. Group 1 (S2V0E0) patients had the best functional outcome gain from treatment, while group 3 (S1V1E0) patients fared less well, particularly with surgical treatment.

Biomarkers and Immunotherapeutic Targets in Glioblastoma.

Glioblastoma (GBM) is an aggressive central nervous system cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides toward changing management strategies. A diverse set of biomarkers have been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR). Emerging theories involving the tumor mutational landscape and microbiome have also been explored in relation to cancer treatment. Although identification of novel biomarkers may improve and help direct treatment of patients with GBM, the next step is to explore the role of biomarkers in precision medicine and selection of specific immunotherapeutic drugs in an individualized manner.

Risk of hemorrhage in patients over age 60 with arteriovenous malformations (AVMs).

Treatment selection for patients 60years of age and older with intracranial arteriovenous malformations (AVMs), requires careful consideration of the natural history and post-treatment hemorrhagic risk. We aimed to directly compare the natural history of AVMs with post-treatment hemorrhagic risk in this population. We retrospectively reviewed our AVM database of 683 patients. Patients ⩾60years at diagnosis were included. Treatment modality was divided into four groups: surgery±embolization (SE), radiosurgery±embolization (RE), embolization only (Emb), and observation (Obs). The natural history of the AVM was defined as the annual risk of hemorrhage under observation. Risk of hemorrhage after treatment was also calculated. Sixty-one patients with complete data were included. Average age was 68.4±7.5years, with 55.7% (n=34) being male. Twenty-seven (44.3%) patients presented with intracerebral hemorrhage (ICH). At last follow-up, modified Rankin Scale was higher in patients with subsequent hemorrhages (p=0.023). Overall, obliteration was 65.5%, with 100.0% in the SE group and 43.8% in the RE group (p<0.001). During an average follow-up period of 2.8±3.2years, six patients (9.8%) experienced hemorrhage, with two (12.5%) in the RE group, three (9.4%) in the Obs group and one (9.1%) in the SE group, corresponding to a natural history of 3.5% annual hemorrhage rate and a post-treatment hemorrhagic risk of 3.6%. This post-treatment hemorrhage risk was 2.4% in the SE group and 4.9% in the RE group. Presenting with ICH (p=0.042) and race (p=0.014) were associated with a higher risk of follow-up hemorrhage. Definitive treatment for AVM patients ⩾60years should be cautiously considered. Despite higher post-treatment obliteration rates, the subsequent hemorrhagic risk may exceed that of its natural history. For AVMs with a high risk for hemorrhage, surgery reduces hemorrhagic risk and achieves the highest rate of obliteration.

Management Outcome of Brainstem Arteriovenous Malformations: The Role of Radiosurgery.

INTRODUCTION: Management decisions for brainstem arteriovenous malformations (AVMs) are complicated by balancing the risks of treatment and natural progression to hemorrhage. The present study seeks to compare radiosurgery and conservative management outcomes in brainstem AVMs. METHODS: We performed a retrospective review of patients with brainstem AVM seen at our institution from 1990 to 2013. Patients missing baseline information or those lost to follow-up were excluded. Clinical and angiographic characteristics and subsequent hemorrhagic risk were evaluated according to brainstem AVM location and treatment modality. RESULTS: We identified 30 patients with brainstem AVM with complete data. Mean age was 41.6 ± 20.3 years, and 53.3% (n = 16) were male. Sixteen (53.3%) presented with hemorrhage. Twelve patients (40.0%) were conservatively managed, and 18 were treated. Sixteen (88.9%) of the treated patients underwent radiosurgery, 1 (5.6%) underwent surgery, and 1 (5.6%) underwent embolization only. Average follow-up period was 4.7 ± 5.7 years, and 5 patients (16.7%) experienced recurrent hemorrhage, 3 of whom were in the radiosurgery group and 2 in the conservative group, giving an annual recurrent hemorrhage risk of 3.7% and 4.8%, respectively. Lesion obliteration was achieved in 8 patients (26.7%). Baseline clinical and angiographic factors were similar between the radiosurgery and conservative group. Obliteration was achieved in 43.8% of those treated with radiosurgery (P = 0.008). Despite similar baseline modified Rankin Scale scores, more patients had improvement of modified Rankin Scale score at last follow-up in the radiosurgery group (P = 0.004). Recurrent hemorrhage during follow-up was similar between the 2 groups (P = 0.887). CONCLUSIONS: Our results suggest that when patients with brainstem AVM are selected cautiously, radiosurgery may achieve obliteration and symptom relief without increasing subsequent hemorrhage risk.

Long-term hemorrhagic risk in pediatric patients with arteriovenous malformations.

OBJECTIVE Compared with the general population, the specific natural history of arteriovenous malformations (AVMs) in pediatric patients is less well understood. Furthermore, few pediatric studies have compared posttreatment hemorrhagic risk and functional outcome across different treatment modalities. The objective of this study was to elucidate these points. METHODS The authors retrospectively reviewed all pediatric patients with AVMs evaluated at their institution between 1990 and 2013. The AVM natural history was represented by hemorrhagic risk during the observation period. For treated patients, the observation period was defined as the interval between diagnosis and treatment. Posttreatment hemorrhagic risk and functional outcomes were also assessed. RESULTS A total of 124 pediatric patients with AVMs were evaluated, and 90 patients (72.6%) were retained through follow-up. The average patient age was 13.3 ± 3.8 years, with a mean follow-up period of 9.95 years. The overall AVM obliteration rate was 59.7%. Radiosurgery had an obliteration rate of 49.0%. Thirteen patients were managed conservatively. Four patients under observation hemorrhaged during a total interval of 429.4 patient-years, translating to an annual risk of 0.9%. Posttreatment hemorrhagic risk by treatment modalities were categorized as follows: surgery ± embolization (0.0%), radiosurgery ± embolization (0.8%), embolization alone (2.8%), surgery + radiosurgery ± embolization (3.5%), and observation (0.8%). A significantly higher risk of posttreatment hemorrhage was observed for patients with hemorrhagic presentation (p = 0.043) in multivariate analysis. Seizure presentation, frontal lobe location, nonheadache presentation, and treatment modality were significantly associated with increased risk of poor functional outcomes. CONCLUSIONS In this study of pediatric patients with AVMs, the natural history of hemorrhage was relatively low at 0.9%. Resection remained the optimal management for hemorrhage control and functional outcome perseverance in these pediatric patients with AVMs. AVM obliteration is a valid treatment goal, especially for patients with ruptured presentation, to prevent further hemorrhages later in life.