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.

Management outcomes of peripontine arteriovenous malformation patients presenting with trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia as the presenting symptom of brain arteriovenous malformation (bAVM) has been rarely reported. Treatment of reported cases has been skewed toward surgery for these scarce, deeply located bAVMs. Here, the authors report their management and outcomes of bAVM patients presenting with ipsilateral trigeminal neuralgia (TN) at their institution. METHODS: This is a retrospective cohort study. The authors' institutional bAVM database was queried for non-hereditary hemorrhagic telangiectasia bAVMs in pontine, cistern, brainstem, trigeminal nerve, or tentorial locations. Patients with complete data were included in a search for trigeminal neuralgia or "facial pain" as the presenting symptom with TN being on the same side as the bAVM. Demographics, TN and bAVM characteristics, management strategies, and outcomes of bAVM and TN management were analyzed. RESULTS: Fifty-seven peripontine bAVMs were identified; 8 (14.0%) of these bAVMs were discovered because of ipsilateral TN, including 4 patients (50%) with facial pain in the V2 distribution. Five patients (62.5%) were treated with carbamazepine as the initial medical therapy, 2 (25%) underwent multiple rhizotomies, and 1 (12.5%) underwent microvascular decompression. None of the patients with TN-associated bAVMs presented with hemorrhage, compared with 25 patients (51%) with bAVMs that were not associated with TN (p < 0.01). TN-associated bAVMs were overall smaller than non-TN-associated bAVMs, but the difference was not statistically significant (1.71 cm vs 2.22 cm, p = 0.117), and the Spetzler-Martin grades were similar. Six patients (75%) underwent radiosurgery to the bAVM (mean dose 1800 cGy, mean target volume 0.563 cm3) and had complete resolution of TN symptoms (100%). The mean time from radiosurgery to TN resolution was 193 (range 21-360) days, and 83.3% of treated TN-associated bAVMs were obliterated via radiosurgery. Two patients (12.5%) were recommended for conservative management, with one undergoing subsequent rhizotomies and another patient died of hemorrhage during follow-up. CONCLUSIONS: TN-associated bAVM is a rare condition with limited evidence for management guidance. Radiosurgery can be safe and effective in achieving durable TN control in patients with TN-associated bAVMs. Despite their deep location and unruptured presentation, obliteration can reach 83.3% with radiosurgery.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day). RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30). CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Early versus late surgical decompression for patients with acute traumatic central cord syndrome: a systematic review and meta-analysis.

BACKGROUND CONTEXT: The optimal decompression time for patients presenting with acute traumatic central cord syndrome (ATCCS) has been debated, and a high level of evidence is lacking. PURPOSE: To compare early (<24 hours) versus late (≥24 hours) surgical decompression for ATCCS. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Medline, PubMed, Embase, and CENTRAL were searched from inception to March 15th, 2023. The primary outcome was American Spinal Injury Association (ASIA) motor score. Secondary outcomes were venous thromboembolism (VTE), total complications, overall mortality, hospital length of stay (LOS), and ICU LOS. The GRADE approach determined certainty in evidence. RESULTS: The nine studies included reported on 5,619 patients, of whom 2,099 (37.35%) underwent early decompression and 3520 (62.65%) underwent late decompression. The mean age (53.3 vs 56.2 years, p=.505) and admission ASIA motor score (mean difference [MD]=-0.31 [-3.61, 2.98], p=.85) were similar between the early and late decompression groups. At 6-month follow-up, the two groups were similar in ASIA motor score (MD= -3.30 [-8.24, 1.65], p=.19). However, at 1-year follow-up, the early decompression group had a higher ASIA motor score than the late decompression group in total (MD=4.89 [2.89, 6.88], p<.001, evidence: moderate), upper extremities (MD=2.59 [0.82, 4.36], p=.004) and lower extremities (MD=1.08 [0.34, 1.83], p=.004). Early decompression was also associated with lower VTE (odds ratio [OR]=0.41 [0.26, 0.65], p=.001, evidence: moderate), total complications (OR=0.53 [0.42, 0.67], p<.001, evidence: moderate), and hospital LOS (MD=-2.94 days [-3.83, -2.04], p<.001, evidence: moderate). Finally, ICU LOS (MD=-0.69 days [-1.65, 0.28], p=.16, evidence: very low) and overall mortality (OR=1.35 [0.93, 1.94], p=.11, evidence: moderate) were similar between the two groups. CONCLUSIONS: The meta-analysis of these studies demonstrated that early decompression was beneficial in terms of ASIA motor score, VTE, complications, and hospital LOS. Furthermore, early decompression did not increase mortality odds. Although treatment decision-making has been individualized, early decompression should be considered for patients presenting with ATCCS, provided that the surgeon deems it appropriate.

Management and outcome predictors of patients with ruptured deep-seated brain arteriovenous malformations.

OBJECTIVE: Decision-making for the management of ruptured deep-seated brain arteriovenous malformations (bAVMs) is controversial. This study aimed to shed light on the treatment outcomes of patients with ruptured deep-seated bAVMs. METHODS: Data on bAVM patients were retrieved from the authors' institutional database, spanning 1990-2021. The outcomes were annual hemorrhage risk (before and after intervention), number of follow-up hemorrhages, bAVM obliteration, poor modified Rankin Scale (mRS) score (i.e., mRS score > 2), worsened mRS score, and mortality. Multivariable Cox and logistic regression analyses were conducted to determine predictors of time-to-event and categorical outcomes, respectively. RESULTS: Of the 1066 patients in the database with brain bAVM, 177 patients harboring ruptured deep-seated bAVMs were included. The pretreatment annual hemorrhage risk was 8.24%, and the posttreatment risk was lowered to 1.65%. In multivariable Cox regression analysis, a prenidal aneurysm (HR 2.388, 95% CI 1.057-5.398; p = 0.036) was associated with a higher risk of follow-up hemorrhage, while definitive treatment (i.e., either surgery or radiosurgery vs endovascular embolization or conservative management) (HR 0.267, 95% CI 0.118-0.602; p = 0.001) was associated with a lower risk of follow-up hemorrhage. In multivariable logistic regression analysis, Spetzler-Martin grades IV and V (OR 0.404, 95% CI 0.171-0.917; p = 0.033) and brainstem arteriovenous malformation (AVM) (OR 0.325, 95% CI 0.128-0.778; p = 0.014) were associated with lower odds of obliteration, while definitive treatment (OR 8.864, 95% CI 3.604-25.399; p = 0.008) was associated with higher obliteration odds. Controlling for baseline mRS score, cerebellar AVM (OR 0.286, 95% CI 0.098-0.731; p = 0.013) and definitive treatment (OR 0.361, 95% CI 0.160-0.807; p = 0.013) were associated with lower odds of a poor mRS score, and definitive treatment (OR 0.208, 95% CI 0.076-0.553; p = 0.001) was associated with lower odds of a worsened mRS score. Furthermore, smoking (OR 6.068, 95% CI 1.531-25.581; p = 0.01) and definitive treatment (OR 0.101, 95% CI 0.024-0.361; p = 0.007) were associated with higher and lower mortality odds, respectively. CONCLUSIONS: A definitive treatment strategy seems to be beneficial in achieving higher obliteration and lower hemorrhage rates while decreasing the odds of a poor mRS score, worsened mRS score, and mortality. In this category of patients, prenidal aneurysms warrant treatment, and smoking cessation should be encouraged.

Interventional approaches to symptomatic Tarlov cysts: a 15-year institutional experience.

BACKGROUND: Tarlov cysts are perineural collections of cerebrospinal fluid most often affecting sacral nerve roots, which may cause back pain, extremity paresthesias and weakness, bladder/bowel dysfunction, and/or sexual dysfunction. The most effective treatment of symptomatic Tarlov cysts, with options including non-surgical management, cyst aspiration and injection of fibrin glue, cyst fenestration, and nerve root imbrication, is debated. METHODS: Retrospective chart review was conducted for 220 patients with Tarlov cysts seen at our institution between 2006 and 2021. Logistic regression analysis was conducted to determine the association between treatment modality, patient characteristics, and clinical outcome. RESULTS: Seventy-two (43.1%) patients with symptomatic Tarlov cysts were managed non-surgically. Of the 95 patients managed interventionally, 71 (74.7%) underwent CT-guided aspiration of the cyst with injection of fibrin glue; 17 (17.9%) underwent cyst aspiration alone; 5 (5.3%) underwent blood patching; and 2 (2.1%) underwent more than one of the aforementioned procedures. Sixty-six percent of treated patients saw improvement in one or more symptoms, with the most improvement in patients after aspiration of cyst with injection of fibrin glue; however, this association was not statistically significant on logistic regression analysis. CONCLUSION: Although the subtype of percutaneous treatment was not significantly associated with optimal or suboptimal patient outcomes, cyst aspiration both with and without injection of fibrin glue may serve as a useful diagnostic tool to (1) determine symptom etiology and (2) identify patients who might have achieved temporary improvement between the time of cyst aspiration and refill with cerebrospinal fluid as potential candidates for neurosurgical intervention of cyst fenestration and nerve root imbrication.

Percutaneous balloon compression for trigeminal neuralgia: experience and surgical techniques from a single institution.

OBJECTIVE: The treatment experience and the technical skill with percutaneous balloon compression (PBC) for treatment of primary trigeminal neuralgia (TN) were summarised in a single institution. METHODS: This is a retrospective review including consecutive patients with typical symptoms of uni-lateral primary TN who underwent PBC from June 2020 to September 2021 in our institution. We excluded secondary aetiologies of TN. Patient demographics, surgical techniques and outcomes were reviewed. All included patients were initially managed with carbamazepine before PBC. RESULTS: A total of 70 patients were included. The mean length of follow-up was 10.6 months. Sixty-nine (98.6%) were successfully treated, and only one patient failed due to particularly narrow foramen ovale. Amongst successfully treated patients, 68 (97.1%) had immediate pain relief, with one having delayed relief. Sixty-eight patients (97.1%) had immediate facial numbness post-operatively and one (1.4%) presented delayed numbness 7 days after surgery. In the last follow-up, regarding facial numbness, 22 (31.9%) patients had complete resolution, whilst 46 (67.6%) had different degrees of benefit. Forty-nine (71.0%) patients developed masseter muscle weakness with recovery at 3-month follow-up. No anaesthesia dolorosa, keratitis, intracranial infection or death occurred in this study. CONCLUSION: PBC for treatment of TN has quick and effective result, and could be safely performed under general anaesthesia without discomfort to the patient. The common postoperative complications are facial numbness and masseter muscle weakness, with most being improved or recovered at follow-up.

Surgery or Endovascular Treatment in Patients with Anterior Communicating Artery Aneurysm: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms. METHODS: Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke. RESULTS: Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63-1.37], P = 0.69), ruptured (OR = 0.92 [0.62-1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06-39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50-1.13], P = 0.17), ruptured (OR = 0.77 [0.49-1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21-1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49-4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33-5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30-9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17-0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11-0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08-3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09-0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29-1.52], P = 0.33). The ORs of other outcomes were similar. CONCLUSIONS: ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence.

Microsurgery Versus Stereotactic Radiosurgery for Treatment of Patients With Brain Arteriovenous Malformation: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment decision-making for brain arteriovenous malformations (bAVMs) with microsurgery or stereotactic radiosurgery (SRS) is controversial. OBJECTIVE: To conduct a systematic review and meta-analysis to compare microsurgery vs SRS for bAVMs. METHOD: Medline and PubMed were searched from inception to June 21, 2022. The primary outcomes were obliteration and follow-up hemorrhage, and secondary outcomes were permanent neurological deficit, worsened modified Rankin scale (mRS), follow-up mRS > 2, and mortality. The GRADE approach was used for grading the level of evidence. RESULTS: Eight studies were included, which yielded 817 patients, of which 432 (52.8%) and 385 (47.1%) patients underwent microsurgery and SRS, respectively. Two cohorts were comparable in age, sex, Spetzler-Martin grade, nidus size, location, deep venous drainage, eloquence, and follow-up. In the microsurgery group, the odds ratio (OR) of obliteration was higher (OR = 18.51 [11.05, 31.01], P < .000001, evidence: high) and the hazard ratio of follow-up hemorrhage was lower (hazard ratio = 0.47 [0.23, 0.97], P = .04, evidence: moderate). The OR of permanent neurological deficit was higher with microsurgery (OR = 2.85 [1.63, 4.97], P = .0002, evidence: low), whereas the OR of worsened mRS (OR = 1.24 [0.65, 2.38], P = .52, evidence: moderate), follow-up mRS > 2 (OR = 0.78 [0.36, 1.7], P = .53, evidence: moderate), and mortality (OR = 1.17 [0.41, 3.3], P = .77, evidence: moderate) were comparable between the groups. CONCLUSION: Microsurgery was superior at obliterating bAVMs and preventing further hemorrhage. Despite a higher rate of postoperative neurological deficit with microsurgery, functional status and mortality were comparable with patients who underwent SRS. Microsurgery should remain a first-line consideration for bAVMs, with SRS reserved for inaccessible locations, highly eloquent areas, and medically high-risk or unwilling patients.

Microsurgery versus Microsurgery With Preoperative Embolization for Brain Arteriovenous Malformation Treatment: A Systematic Review and Meta-analysis.

BACKGROUND: Preoperative embolization has traditionally been regarded as a safe and effective adjunct to microsurgical treatment of brain arteriovenous malformations (bAVM). However, there is currently no high-level evidence to ascertain this presumption. OBJECTIVE: To compare the outcomes of microsurgery (MS) vs microsurgery with preoperative embolization (E + MS) in patients with bAVM through systematic review. METHODS: We searched MEDLINE, PubMed, and Embase. The primary outcome was bAVM obliteration. Secondary outcomes were intraoperative bleeding (mL), complications, worsened modified Rankin Scale (mRS), and mortality. The pooled proportions of outcomes were calculated through the logit transformation method. The odds ratio (OR) of categorical data and mean difference of continuous data were estimated through the Mantel-Haenszel and the inverse variance methods, respectively. RESULTS: Thirty-two studies met the eligibility criteria. One thousand eight hundred twenty-eight patients were treated by microsurgery alone, and 1088 were treated by microsurgery with preoperative embolization, respectively. The meta-analysis revealed no significant difference in AVM obliteration (94.1% vs 95.6%, OR = 1.15 [0.63-2.11], P = .65), mortality (1.7% vs 2%, OR = 0.88 [0.30-2.58], P = .82), procedural complications (18.2% vs 27.2%, OR = 0.47 [0.19-1.17], P = .10), worsened mRS (21.2% vs 18.5%, OR = 1.08 [0.33-3.54], P = .9), and intraoperative blood loss (mean difference = 182.89 [-87.76, 453.55], P = .19). CONCLUSION: The meta-analysis showed no significant difference in AVM obliteration, mortality, complications, worse mRS, and intraoperative blood loss between MS and E + MS groups. For AVMs where MS alone has acceptable results, it is reasonable to bypass unnecessary preoperative embolization given higher postoperative complication risk.

Sacrifice or preserve the superior petrosal vein in microvascular decompression surgery: a systematic review and meta-analysis.

OBJECTIVE: In microvascular decompression (MVD) surgery through the retrosigmoid approach, the surgeon may have to sacrifice the superior petrosal vein (SPV). However, this is a controversial maneuver. To date, high-level evidence comparing the operative outcomes of patients who underwent MVD with and without SPV sacrifice is lacking. Therefore, this study sought to bridge this gap. METHODS: The authors searched the Medline and PubMed databases with appropriate Medical Subject Heading (MeSH) terms and keywords. The primary outcome was vascular-related complications; secondary outcomes were new neurological deficit, cerebrospinal fluid (CSF) leak, and neuralgia relief. The pooled proportions of outcomes and OR (95% CI) for categorical data were calculated by using the logit transformation and Mantel-Haenszel methods, respectively. RESULTS: Six studies yielding 1143 patients were included, of which 618 patients had their SPV sacrificed. The pooled proportion (95% CI) values were 3.82 (0.87-15.17) for vascular-related complications, 3.64 (1.0-12.42) for new neurological deficits, 2.85 (1.21-6.58) for CSF leaks, and 88.90 (84.90-91.94) for neuralgia relief. The meta-analysis concluded that, whether the surgeon sacrificed or preserved the SPV, the odds were similar for vascular-related complications (2.5% vs 1.5%, OR [95% CI] 1.01 [0.33-3.09], p = 0.99), new neurological deficits (1.2% vs 2.8%, OR [95% CI] 0.55 [0.18-1.66], p = 0.29), CSF leak (3.1% vs 2.1%, OR [95% CI] 1.16 [0.46-2.94], p = 0.75), and neuralgia relief (86.6% vs 87%, OR [95% CI] 0.96 [0.62-1.49], p = 0.84). CONCLUSIONS: SPV sacrifice is as safe as SPV preservation. The authors recommend intentional SPV sacrifice when gentle retraction fails to enhance surgical field visualization and if the surgeon encounters SPV-related neurovascular conflict and/or anticipates impeding SPV-related bleeding.

Natural history and treatment of deep-seated brain arteriovenous malformations in pediatric patients.

OBJECTIVE: Pediatric deep brain arteriovenous malformations (bAVMs) represent a unique management challenge given their higher cumulative risk of hemorrhage as well as a higher risk of treatment. Better understanding of hemorrhage risk in this patient population will lead to a better decision-making process for patient management. METHODS: The authors retrospectively reviewed their institutional bAVM database from 1990 to 2019 and included patients younger than 21 years who had deep-seated bAVMs. They present the annual hemorrhage risk, during the natural history and after treatment, and functional outcomes. RESULTS: Thirty-one pediatric patients were included in this study (13 males and 18 females) with a mean age of 11.8 (SD 4.4) years. The most frequent presenting symptoms were headache (54.8%), weakness (38.7%), and seizure (22.6%). The mean follow-up duration was 13.14 (SD 12.5) years, during which 7 (22.6%) AVMs were obliterated, 10 (32.3%) individuals experienced hemorrhage, and the modified Rankin Scale score worsened in 8 (25.8%) patients. The annual natural history risk of hemorrhage was 3.24% per patient, and the overall annual hemorrhage risk after treatment was 1.98% per patient. In particular, the risk was reduced to 0.64% per patient in the stereotactic radiosurgery (SRS) group. Non-White race showed a trend of higher rupture at presentation (OR 5 [95% CI 0.84-41.68], p = 0.09). Female sex was associated with higher odds (OR 13.076 [95% CI 1.424-333.591], p = 0.048) and SRS was associated with lower odds (OR 0.122 [95% CI 0.011-0.862], p = 0.049) of follow-up hemorrhage. CONCLUSIONS: Given the substantial cumulative risk of lifelong hemorrhagic stroke in pediatric patients, timely definitive treatment is warranted. SRS may be beneficial when the risk-benefit profile is deemed acceptable.

Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain.

Trigeminal neuralgia, historically dubbed the "suicide disease," is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)-approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery. Here, we identify the NRF2 transcriptional network as a potential therapeutic target. We report that cerebrospinal fluid from patients with trigeminal neuralgia accumulates reactive oxygen species, several of which directly activate the pain-transducing channel TRPA1. Similar to our patient cohort, a mouse model of trigeminal neuropathic pain also exhibits notable oxidative stress. We discover that stimulating the NRF2 antioxidant transcriptional network is as analgesic as inhibiting TRPA1, in part by reversing the underlying oxidative stress. Using a transcriptome-guided drug discovery strategy, we identify two NRF2 network modulators as potential treatments. One of these candidates, exemestane, is already FDA-approved and may thus be a promising alternative treatment for trigeminal neuropathic pain.

Timing of Revascularization in Ischemic Moyamoya Disease: Association of Early Versus Delayed Surgery with Perioperative and Long-Term Outcomes.

OBJECTIVE: Patients with nmoyamoya disease (MMD) who present primarily with ischemic stroke are known to have greater rates of perioperative strokes as compared with those who present with nonstroke symptoms. The optimal timing for revascularization for these patients remains unclear. METHODS: From 1994 to 2015, 91 patients with MMD presented with signs and symptoms of an acute ischemic stroke with diffusion restriction correlate on magnetic resonance imaging, and these patients were subdivided into those who underwent early revascularization (<90 days from last stroke), versus those who underwent delayed revascularization (≥90 days after last stroke), based on evidence that most neurological recovery after stroke occurs during the first three months. Perioperative and long-term outcomes were compared between the 2 surgical cohorts. RESULTS: In total, 27 patients underwent early revascularization, and 64 patients underwent delayed revascularization. Patients who underwent early revascularization had a statistically greater rate of perioperative stroke (P = 0.04) and perioperative mortality (P = 0.03), and overall complication rate (P = 0.049). At last follow-up of 5.2 ± 4.3 years, patients who underwent delayed revascularization had a lower mortality rate (P = 0.01) and a lower overall postoperative stroke incidence (P = 0.002). As a function of time, patients with MMD undergoing delayed revascularization had a statistically higher length of stroke-free survival (P = 0.005). CONCLUSIONS: Patients with MMD who present with ischemic stroke are more likely to have perioperative strokes, overall perioperative complications, worse long-term mortality rates, and lower rates of stroke-free survival if revascularization surgery occurred within 90 days of last stroke.

Both subthalamic and pallidal deep brain stimulation are effective for GNAO1-associated dystonia: three case reports and a literature review.

Background: Mutations in the G-protein subunit alpha o1 (GNAO1) gene have recently been shown to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. The clinical manifestations of GNAO1-associated movement disorders are highly heterogeneous. However, the genotype-phenotype correlations in this disease remain unclear, and the treatments for GNAO1-associated movement disorders are still limited. Objective: The objective of this study was to explore diagnostic and therapeutic strategies for GNAO1-associated movement disorders. Methods: This study describes the cases of three Chinese patients who had shown severe and progressive dystonia in the absence of epilepsy since early childhood. We performed genetic analyses in these patients. Patients 1 and 2 underwent globus pallidus internus (GPi) deep brain stimulation (DBS) implantation, and Patient 3 underwent subthalamic nucleus (STN) DBS implantation. In addition, on the basis of a literature review, we summarized and discussed the clinical characteristics and outcomes after DBS surgery for all reported patients with GNAO1-associated movement disorders. Results: Whole-exome sequencing (WES) analysis revealed de novo variants in the GNAO1 gene for all three patients, including a splice-site variant (c.724-8G > A) in Patients 1 and 3 and a novel heterozygous missense variant (c.124G > A; p. Gly42Arg) in Patient 2. Both GPi and STN DBS were effective in improving the dystonia symptoms of all three patients. Conclusion: DBS is effective in ameliorating motor symptoms in patients with GNAO1-associated movement disorders, and both STN DBS and GPi DBS should be considered promptly for patients with sustained refractory GNAO1-associated dystonia.

Revascularization of Hemorrhagic Moyamoya Disease in a North American Cohort: The Role of Timing in Perioperative and Long-Term Outcomes.

BACKGROUND: Several East Asian studies have examined the role of revascularization in the context of hemorrhagic moyamoya disease (MMD) and found a decrease in postoperative rehemorrhage rates. To date, no data exist comparing revascularization with conservative management in North American patients with hemorrhagic MMD. OBJECTIVE: To compare the clinical outcomes of conservative management vs surgical revascularization for North American patients with hemorrhagic MMD and investigate the effect of revascularization timing. METHODS: We retrospectively studied the mortality and stroke-free survival of patients with MMD presenting with hemorrhagic stroke between 1994 and 2015. RESULTS: The diagnosis of hemorrhagic MMD was established in 38 patients. Seventeen patients were managed conservatively, and 21 were surgically revascularized. Twelve patients underwent revascularization within 6 months of hemorrhage, and 9 underwent surgery in a delayed fashion. Six conservatively managed patients (35.3%) died within the follow-up period compared with 0 (0%) surgically revascularized patients, P = .004. Conservatively managed patients also experienced an increased number of postoperative strokes, P = .037, and shorter stroke-free survival compared with patients undergoing revascularization, P = .047. On multivariate analysis, increased age, worse baseline modified Rankin score, and conservative management were independently associated with worse neurological outcomes, P < .05. Early revascularization was associated with higher rates of postoperative seizures, P = .033, and wound complications, P = .031, compared with those who underwent delayed surgery. CONCLUSION: Conservative management in a North American patient cohort was associated with greater mortality and worsened neurological outcomes compared with those undergoing revascularization. Early revascularization was associated with higher rates of postoperative seizures and wound complications, although these risks must be balanced against the risk of rehemorrhage.

Comparison of adult and pediatric pilocytic astrocytomas using competing risk analysis: A population-based study.

BACKGROUND: Pilocytic astrocytoma(PA) is a relatively benign tumor occurring primarily in the pediatric population. Comparison of characteristics and survival of this tumor between adult and pediatric patients in a single, population-based study is yet to be performed. OBJECTIVE: We aimed to directly compare the characteristics and survival of pilocytic astrocytoma between pediatric and adult patients in a single, population-based study. METHODS: We utilized the SEER database using data from 1983 to 2016. All patients with histologically confirmed, intracranial pilocytic astrocytoma were included and divided into a pediatric(age<18 years) or adult group. Due to lower risk of tumor-specific-mortality, we utilized a competing risk analysis to account for mortality from other causes. Univariable and multivariable competing risk analysis(CRA) was performed, and sub-distribution hazard ratio(SHR) or adjusted SHR(aSHR) was reported. RESULTS: A total of 4357 patients comprised the final cohort, with 3014(69.2%) pediatric patients. As compared to the pediatric group, adult patients were predominantly White(p < 0.01), with PA less likely fully resected(p = 0.01), smaller tumor size(p < 0.01), and were less often located in the cerebellum(p < 0.01). Multivariable CRA revealed a worse prognosis for the adult group(p < 0.01), regional or distal extension(p < 0.01), and non-cerebellar locations including frontal(p < 0.01), parietal(p < 0.01), ventricular(p < 0.01) or brainstem(p < 0.01). Improved prognosis was seen with more recent year-of-diagnosis(2003-2016, p = 0.03), gross-total/total resection(p < 0.01), and biopsy only patients(p = 0.02). CONCLUSIONS: Pilocytic astrocytomas in adult patients have a worse prognosis than pediatric patients. Cumulative incidence of cancer-specific-mortality is higher in adults when adjusted for other factors. PAs with regional or distal extension and non-cerebellar locations carry worse outcomes. Surgery remains an effective treatment and GTR/TR should be achieved when possible.

Microsurgical resection versus stereotactic radiosurgery for low-grade intracranial arteriovenous malformations: A 27-year institutional experience.

The role of microsurgery and radiosurgery in the management of low-grade (Spetzler-Martin grade 1 and 2) arteriovenous malformations (AVMs) remains controversial. We aimed to compare outcomes of low-grade AVMs following microsurgery and radiosurgery using a database of AVM patients presenting between 1990 and 2017. Procedure-related complications, obliteration, and functional status at last follow-up were compared between groups. Hemorrhage-free survival was compared using Kaplan-Meier analysis with subgroup analyses by rupture status on presentation. The study involved 233 patients, of which 113 and 120 were treated with microsurgery and radiosurgery, respectively. The complication rates were statistically comparable between both treatment modalities. Mean follow-up time was 5.1 ± 5.2 years. In the complete cohort, there was no significant difference in hemorrhage-free survival between microsurgery and radiosurgery (log-rank p = 0.676, Breslow p = 0.493). When excluding procedure-related hemorrhage and partial resection, hemorrhage-free survival was significantly higher in the surgically treated cohort (log-rank = 0.094, Breslow p = 0.034). The obliteration rate was significantly higher in the surgical cohort (96% vs. 57%, p < 0.001), while functional status was similar. Microsurgery may offer superior hemorrhage-free survival in the early post-treatment period and demonstrates equivalent long-term hemorrhage control and functional outcome at 5 years compared to radiosurgery with nearly complete obliteration rates. Persistent neurologic deficits following microsurgery and symptomatic cerebral edema represent important treatment risks despite low SM grading. Appropriate patient selection even when dealing with low-grade AVMs is advised, as judicious patient selection and emphasis on technical success can minimize procedure-related hemorrhage and the incidence of subtotal resection.

Comparison of management approaches in deep-seated intracranial arteriovenous malformations: Does treatment improve outcome?

Deep-seated intracranial arteriovenous malformations (AVMs) represent a subset of AVMs characterized by variably reported outcomes regarding the risk of hemorrhage, microsurgical complications, and response to stereotactic radiosurgery (SRS). We aimed to compare outcomes of microsurgery, SRS, endovascular therapy, and conservative follow-up in deep-seated AVMs. A prospectively maintained database of AVM patients (1990-2017) was queried to identify patients with ruptured and unruptured deep-seated AVMs (extension into thalamus, basal ganglia, or brainstem). Comparisons of hemorrhage-free survival and poor functional outcome (modified Rankin scale [mRS] > 2) were performed between conservative management, microsurgery (±pre-procedural embolization), SRS (±pre-procedural embolization), and embolization utilizing multivariable Cox and logistic regression analyses controlling for univariable factors with p < 0.05. Of 789 AVM patients, 102 had deep-seated AVMs (conservative: 34; microsurgery: 6; SRS: 54; embolization: 8). Mean follow-up time was 6.1 years and did not differ significantly between management groups (p = 0.393). Complete obliteration was achieved in 49% of SRS patients. Upon multivariable analysis controlling for baseline rupture with conservative management as a reference group, embolization was associated with an increased hazard of hemorrhage (HR = 6.2, 95%CI [1.1-40.0], p = 0.037), while microsurgery (p = 0.118) and SRS (p = 0.167) provided no significant protection from hemorrhage. Controlling for baseline mRS, microsurgery was associated with an increased risk of poor outcome (OR = 9.2[1.2-68.3], p = 0.030), while SRS (p = 0.557) and embolization (p = 0.541) did not differ significantly from conservative management. Deep AVMs harbor a high risk of hemorrhage, but the benefit from intervention Remains uncertain. SRS may be a relatively more effective approach if interventional therapy is indicated.

Hemorrhage Following Complete Arteriovenous Malformation Resection With No Detectable Recurrence: Insights From a 27-Year Registry.

BACKGROUND: Although recurrence and de novo formation of arteriovenous malformations (AVMs) have been reported following complete resection, the occurrence of hemorrhage in the same location of an AVM with no detectable lesion (lesion-negative hemorrhage) has not been described after microsurgery. OBJECTIVE: To characterize the incidence and properties of lesion-negative hemorrhage following complete microsurgical resection. METHODS: A prospectively maintained registry of AVM patients seen at our institution between 1990 and 2017 was used. Microsurgically treated patients were selected, and the incidence of a lesion-negative hemorrhage was calculated and described with a Kaplan-Meier curve. Baseline characteristics as well as functional outcome at last follow-up were compared between patients with and without a lesion-negative hemorrhage. RESULTS: From a total of 789 AVM patients, 619 (79%) were treated, and 210 out of 619 patients (34%) underwent microsurgery with or without preoperative embolization or radiosurgery. The microsurgically treated cohort was followed up for a mean of 6.1 ± 3.0 yr after surgery with 5 (2.4%) patients experiencing postresection lesion-negative hemorrhage (3.9 per 1000 person-years) at an average of 8.6 ± 9.0 yr following surgery. Follow-up angiograms after hemorrhage (up to 2 mo posthemorrhage) confirmed the absence of a recurrent or de novo AVM in all cases. All patients with a lesion-negative hemorrhage initially presented with rupture before resection (Fisher P = .066; log-rank P = .057). The occurrence of a lesion-negative hemorrhage was significantly associated with worse modified Rankin scale scores at last follow-up (P = .031). CONCLUSION: A lesion-negative hemorrhage can occur following complete microsurgical resection in up to 2.4% of patients. Exploration of possible underlying causes is warranted.