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Background: Occipital neuralgia (ON) is a debilitating headache disorder. Due to the rarity of this disorder and lack of high-level evidence, a clear framework for choosing the optimal surgical approach for medically refractory ON incorporating shared decision making with patients does not exist., Methods: A literature review of studies reporting pain outcomes of patients who underwent surgical treatment for ON was performed, as well as a retrospective chart review of patients who underwent surgery for ON within our institution., Results: Thirty-two articles met the inclusion criteria. A majority of the articles were retrospective case series (22/32). The mean number of patients across the studies was 34 (standard deviation (SD) 39). Among the 13 studies that reported change in pain score on 10-point scales, a study of 20 patients who had undergone C2 and/or C3 ganglionectomies reported the greatest reduction in pain intensity after surgery. The studies evaluating percutaneous ablative methods including radiofrequency ablation and cryoablation showed the smallest reduction in pain scores overall. At our institution from 2014 to 2023, 11 patients received surgical treatment for ON with a mean follow-up of 187 days (SD 426)., Conclusion: Based on these results, the first decision aid for selecting a surgical approach to medically refractory ON is presented. The algorithm prioritizes nerve sparing followed by non-nerve sparing techniques with the incorporation of patient preference. Shared decision making is critical in the treatment of ON given the lack of clear scientific evidence regarding the superiority of a particular surgical method., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brain stimulation (BStim) encompasses multiple modalities (e.g., deep brain stimulation, responsive neurostimulation) that utilize electrodes implanted in deep brain structures to treat neurological disorders. Currently, BStim is primarily used to treat movement disorders such as Parkinson's, though indications are expanding to include neuropsychiatric disorders like depression and schizophrenia. Traditional BStim systems are "open-loop" and deliver constant electrical stimulation based on manually-determined parameters. Advancements in BStim have enabled development of "closed-loop" systems that analyze neural biomarkers (e.g., local field potentials in the sub-thalamic nucleus) and adjust electrical modulation in a dynamic, patient-specific, and energy efficient manner. These closed-loop systems enable real-time, context-specific stimulation adjustment to reduce symptom burden. Machine learning (ML) has emerged as a vital component in designing these closed-loop systems as ML models can predict / identify presence of disease symptoms based on neural activity and adaptively learn to modulate stimulation. We queried the US National Library of Medicine PubMed database to understand the role of ML in developing closed-loop BStim systems to treat epilepsy, movement disorders, and neuropsychiatric disorders. Both neural and non-neural network ML algorithms have successfully been leveraged to create closed-loop systems that perform comparably to open-loop systems. For disorders in which the underlying neural pathophysiology is relatively well understood (e.g., Parkinson's, essential tremor), most work has involved refining ML models that can classify neural signals as aberrant or normal. The same is seen for epilepsy, where most current research has focused on identifying optimal ML model design and integrating closed-loop systems into existing devices. For neuropsychiatric disorders, where the underlying pathologic neural circuitry is still being investigated, research is focused on identifying biomarkers (e.g., local field potentials from brain nuclei) that ML models can use to identify onset of symptoms and stratify severity of disease., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Chiari Malformation Type I (CMI) is a congenital malformation diagnosed by MRI findings of at least 5 mm of cerebellar ectopy below the foramen magnum. CM1 is frequently associated with syringomyelia. Herein, we discuss the history of CMI and syringomyelia, including early pathological and surgical studies. We also describe recent investigations into the pathogenesis and pathophysiology of CMI and their practical implications on management and surgical intervention. We also highlight the recent development of the Common Data Elements for CMI, providing a framework for ongoing investigations. Finally, we discuss current controversies of surgical management in CMI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments such as tremor, bradykinesia, dyskinesia, and gait abnormalities. Current protocols assess PD symptoms during clinic visits and can be subjective. Patient diaries can help clinicians evaluate at-home symptoms, but can be incomplete or inaccurate. Therefore, researchers have developed in-home automated methods to monitor PD symptoms to enable data-driven PD diagnosis and management. We queried the US National Library of Medicine PubMed database to analyze the progression of the technologies and computational/machine learning methods used to monitor common motor PD symptoms. A sub-set of roughly 12,000 papers was reviewed that best characterized the machine learning and technology timelines that manifested from reviewing the literature. The technology used to monitor PD motor symptoms has advanced significantly in the past five decades. Early monitoring began with in-lab devices such as needle-based EMG, transitioned to in-lab accelerometers/gyroscopes, then to wearable accelerometers/gyroscopes, and finally to phone and mobile & web application-based in-home monitoring. Significant progress has also been made with respect to the use of machine learning algorithms to classify PD patients. Using data from different devices (e.g., video cameras, phone-based accelerometers), researchers have designed neural network and non-neural network-based machine learning algorithms to categorize PD patients across tremor, gait, bradykinesia, and dyskinesia. The five-decade co-evolution of technology and computational techniques used to monitor PD motor symptoms has driven significant progress that is enabling the shift from in-lab/clinic to in-home monitoring of PD symptoms., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: Chronic adhesive spinal arachnoiditis (SA) is a complex disease process that results in spinal cord tethering, CSF flow blockage, intradural adhesions, spinal cord edema, and sometimes syringomyelia. When it is focal or restricted to fewer than 3 spinal segments, the disease responds well to open surgical approaches. More extensive arachnoiditis extending beyond 4 spinal segments has a much worse prognosis because of less adequate removal of adhesions and a higher propensity for postoperative scarring and retethering. Flexible neuroendoscopy can extend the longitudinal range of the surgical field with a minimalist approach. The authors present a cohort of patients with severe cervical and thoracic arachnoiditis and myelopathy who underwent flexible endoscopy to address arachnoiditis at spinal segments not exposed by open surgical intervention. These observations will inform subsequent efforts to improve the treatment of extensive arachnoiditis., Methods: Over a period of 3 years (2017-2020), 10 patients with progressive myelopathy were evaluated and treated for extensive SA. Seven patients had syringomyelia, 1 had spinal cord edema, and 2 had spinal cord distortion. Surgical intervention included 2- to 5-level thoracic laminectomy, microscopic lysis of adhesions, and then lysis of adhesions at adjacent spinal levels performed using a rigid or flexible endoscope. The mean follow-up was 5 months (range 2-15 months). Neurological function was examined using standard measures. MRI was used to assess syrinx resolution., Results: The mean length of syringes was 19.2 ± 10 cm, with a mean maximum diameter of 7.0 ± 2.9 mm. Patients underwent laminectomies averaging 3.7 ± 0.9 (range 2-5) levels in length followed by endoscopy, which expanded exposure by an average of another 2.4 extra segments (6.1 ± 4.0 levels total). Endoscopic dissection of extensive arachnoiditis in the dorsal subarachnoid space proceeded through a complex network of opaque arachnoidal bands and membranes bridging from the dorsal dura mater to the spinal cord. In less severely problematic areas, the arachnoid membrane was transparent and attached to the spinal cord through multifocal arachnoid adhesions bridging the subarachnoid space. The endoscope did not compress or injure the spinal cord., Conclusions: Intrathecal endoscopy allowed visual assessment and safe removal of intradural adhesions beyond the laminectomy margins. Further development of this technique should improve its effectiveness in opening the subarachnoid space and untethering the spinal cord in cases of extensive chronic adhesive SA.

Objective: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors., Methods: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes., Results: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006)., Conclusions: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Background: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes., Objective: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features., Methods: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation., Results: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts., Conclusion: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates., Objective: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study., Methods: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes., Results: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar., Conclusion: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus., Methods: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death., Results: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively., Conclusions: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Background: Dissecting aneurysms of the posterior cerebral circulation can wield significant treatment challenges with devastating clinical outcomes. Despite an expanded therapeutic armamentarium, these vascular lesions remain relatively difficult to diagnose and portend high associated morbidity and mortality., Methods: A ruptured, fusiform, dissecting aneurysm of the mid V4 segment of the right vertebral artery (VA) distal to the posterior inferior cerebellar artery origin resulted in a Hunt and Hess grade 5, Fisher scale score 4 subarachnoid hemorrhage. The lesion incorporated 360 degrees of the vessel wall and extended across an area measuring 11 mm in length and 6.8 mm in width at maximum dimension. The vascular lesion was treated with 2 overlapping Pipeline Embolization Devices., Results: Digital subtraction angiography demonstrated an origin of the right posterior inferior cerebellar artery mildly stenosed by the dissecting aneurysm. The left VA was markedly hypoplastic. After deployment of 2 overlapping Pipeline Embolization Devices, the aneurysm neck was well covered with appropriate positioning of the stent construct with good apposition to the vessel wall. There was contrast stasis within the aneurysm. The patient was managed with dual antiplatelet therapy. He demonstrated initial clinical and radiographic improvement. However, on the night of the second postprocedure day, the patient succumbed to rerupture of the aneurysm., Conclusions: The literature posits that nonsaccular, fusiform, and dissecting aneurysms of the vertebrobasilar circulation can be occluded with consistency and success using flow diversion techniques. Endovascular treatment of a ruptured dissecting aneurysm of the VA is technically feasible and can be performed with or without parent artery occlusion. Outcomes following flow diversion of the posterior circulation may depend on the location of the dissection and viability of collateral circulation. In the present case, adequate coverage of the aneurysm did not portend a positive outcome., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Predicting future hemorrhage risk may allow better selection of patients with cerebral cavernous malformations (CCMs) who will likely benefit from treatment. In this study, we sought to identify predictors of CCM hemorrhage, and to compare subsequent symptomatic hemorrhage risks between patients with and without previous hemorrhage., Methods: We performed a retrospective review of consecutive CCM patients at our institution between 1982 and 2017. Patients with diffuse or familial CCM syndromes, and those without follow-up data were excluded. The primary endpoint was acute symptomatic hemorrhage causing transient or permanent neurological symptoms. Primary endpoint incidences were compared between patients with and without previous hemorrhage., Results: The study cohort comprised 84 patients with 90 CCMs. Previous hemorrhage was the only significant predictor for the primary endpoint (P = 0.003). CCMs with previous hemorrhage had a higher risk of symptomatic hemorrhage in follow-up than those without previous hemorrhage (26.9 vs. 1.5 symptomatic hemorrhages per 1000 CCM-months, P < 0.001). CCMs with and without previous hemorrhage had annual hemorrhage rates of 2.7% and 0.15%, respectively. Symptomatic hemorrhage-free survival rates were significantly lower in CCMs with previous hemorrhage (log-rank test, P < 0.001). Actuarial hemorrhage-free survival rates for CCMs with previous hemorrhage were 75%, 60%, 60%, and 60% at 1, 2, 3, and 4 years, respectively, compared with rates of 95%, 95%, 95%, and 84% for CCMs without previous hemorrhage., Conclusions: Previous hemorrhage is a predictor of subsequent symptomatic hemorrhage in CCMs. Compared with CCMs without previous hemorrhage, those with prior hemorrhage have a significantly higher risk of future symptomatic hemorrhage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Gamma Knife radiosurgery (GKRS) provides a safe and effective management option for patients with all types of pituitary adenomas. The long-term adverse effects of targeted radiation to the hypothalamic-pituitary axis in relationship to radiation dose remain unclear. In this retrospective review, the authors investigated the role of differential radiation doses in predicting long-term clinical outcomes and pituitary function after GKRS for pituitary adenomas., Methods: A cohort of 236 patients with pituitary tumors (41.5% nonfunctioning, 58.5% functioning adenomas) was treated with GKRS between 1998 and 2015. Point dosimetric measurements, with no minimum volume, to 14 consistent points along the hypothalamus bilaterally, pituitary stalk, and normal pituitary were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiological, and endocrine outcomes., Results: With a median follow-up duration of 42.9 months, 18.6% of patients developed new loss of pituitary function. The median time to endocrinopathy was 21 months (range 2-157 months). The median dose was 2.1 Gy to the hypothalamus, 9.1 Gy to the pituitary stalk, and 15.3 Gy to the normal pituitary. Increasing age (p = 0.015, HR 0.98) and ratio of maximum dose to the pituitary stalk over the normal pituitary gland (p = 0.013, HR 0.22) were independent predictors of new or worsening hypopituitarism in the multivariate analysis. Sex, margin dose, treatment volume, nonfunctioning adenoma status, or ratio between doses to the pituitary stalk and hypothalamus were not significant predictors., Conclusions: GKRS offers a low rate of delayed pituitary insufficiency for pituitary adenomas. Doses to the hypothalamus are low and generally do not portend endocrine deficits. Patients who are treated with a high dose to the pituitary stalk relative to the normal gland are at higher risk of post-GKRS endocrinopathy. Point dosimetry to specific neuroanatomical structures revealed that a ratio of stalk-to-gland radiation dose of 0.8 or more significantly increased the risk of endocrinopathy following GKRS. Improvement in the gradient index toward the stalk and normal gland may help preserve endocrine function.

Objective: Stereotactic radiosurgery (SRS) is a commonly employed treatment modality for brain arteriovenous malformations (AVMs). However, due to the low frequency of delayed cyst formation after AVM SRS, as well as the prolonged time interval between treatment and its occurrence, the characteristics of post-SRS cyst formation are not well defined. Therefore, the aims of this retrospective cohort study are to determine the rate of cyst formation after SRS for AVMs, identify predictive factors, and evaluate the clinical sequelae of post-SRS cysts., Methods: The authors analyzed an SRS database for AVM patients who underwent SRS at the University of Virginia and identified those who developed post-SRS cysts. Statistical analyses were performed to determine predictors of post-SRS cyst formation and the effect of cyst formation on new or worsening seizures after SRS., Results: The study cohort comprised 1159 AVM patients treated with SRS; cyst formation occurred in 17 patients (post-SRS cyst rate of 1.5%). Compared with patients who did not develop post-SRS cysts, those with cyst formation were treated with a greater number of radiosurgical isocenters (mean 3.8 vs 2.8, p = 0.047), had a longer follow-up (mean 132 vs 71 months, p < 0.001), were more likely to develop radiological radiation-induced changes (RIC) (64.7% vs 36.1%, p = 0.021), and had a longer duration of RIC (57 vs 21 months, p < 0.001). A higher number of isocenters (p = 0.014), radiological RIC (p = 0.002), and longer follow-up (p = 0.034) were found to be independent predictors of post-SRS cyst formation in the multivariate analysis. There was a trend toward a significant association between cyst formation and new or worsening seizures in univariate analysis (p = 0.054)., Conclusions: Patients with greater nidal complexity appear to be more prone to post-SRS cyst formation. The findings of this study emphasize the importance of long-term follow-up for patients who have undergone AVM SRS, even after nidal obliteration is achieved. Post-SRS cysts may be epileptogenic, although seizure outcomes after AVM SRS are multifactorial.

Nasoethmoid schwannomas with significant intracranial extension are rare tumours that typically present with visual and olfactory deficits. We describe a nasoethmoid schwannoma in a patient who was completely asymptomatic. Despite impressive intracranial involvement, nasoethmoid schwannomas may present asymptomatically and should be considered in the differential of contrast-enhancing anterior skull base lesions.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Stenosis of the transverse sinus (TS) and sigmoid sinus (SS), with a trans-stenosis pressure gradient, has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH). MRI has shown improvement in TS and SS stenosis after high-volume lumbar puncture (HVLP) in a subset of patients with IIH. The authors present the first report of an IIH patient with immediate post-HVLP TS and SS trans-stenosis pressure gradient reduction and an attendant increase in TS and SS cross-sectional area confirmed using intravascular ultrasonography (IVUS). Recurrence of the patient's TS-SS stenosis coincided with elevated HVLP opening pressure, and venous sinus stent placement resulted in clinical improvement. This report suggests that TS and SS stenosis may be a downstream effect of elevated intracranial pressure in IIH, rather than its principal etiological mechanism. However, the authors hypothesize that endovascular stenting may obliterate a positive feedback loop involving trans-stenosis pressure gradients, and still benefit appropriately selected patients.

OBJECTIVE Cyst formation can occasionally occur after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs). Given the limited data regarding post-SRS cyst formation in patients with AVM, the time course, natural history, and management of this delayed complication are poorly defined. The aim of this systematic review was to determine the incidence, time course, and optimal management of cyst formation after SRS for AVMs. METHODS A literature review was performed using PubMed to identify studies reporting cyst formation in AVM patients treated with SRS. Baseline and outcomes data, including the incidence and management of post-SRS cysts, were extracted from each study that reported follow-up duration. The mean time to cyst formation was calculated from the subset of studies that reported individual patient data. RESULTS Based on pooled data from 22 studies comprising the incidence analysis, the overall rate of post-SRS cyst formation was 3.0% (78/2619 patients). Among the 26 post-SRS cyst patients with available AVM obliteration data, nidal obliteration was achieved in 20 (76.9%). Of the 64 cyst patients with available symptomatology and management data, 21 (32.8%) were symptomatic; 21 cysts (32.8%) were treated with surgical intervention, whereas the remaining 43 (67.2%) were managed conservatively. Based on a subset of 19 studies reporting individual time-to-cyst-formation data from 63 patients, the mean latency period to post-SRS cyst formation was 78 months (6.5 years). CONCLUSIONS Cyst formation is an uncommon complication after SRS for AVMs, with a relatively long latency period. The majority of post-SRS cysts are asymptomatic and can be managed conservatively, although enlarging or symptomatic cysts may require surgical intervention. Long-term follow-up of AVM patients is crucial to the appropriate diagnosis and management of post-SRS cysts.

Objective: Safety and efficacy of superior sagittal sinus (SSS) stenting for non-thrombotic intracranial venous occlusive disease (VOD) is unknown. The aim of this retrospective cohort study is to evaluate outcomes after SSS stenting., Methods: We evaluated an institutional database to identify patients who underwent SSS stenting. Radiographic and clinical outcomes were analyzed and a novel angiographic classification of the SSS was proposed., Results: We identified 19 patients; 42% developed SSS stenosis after transverse sinus stenting. Pre-stent maximum mean venous pressure (MVP) in the SSS of 16.2 mm Hg decreased to 13.1 mm Hg after stenting (p=0.037). Preoperative trans-stenosis pressure gradient of 4.2 mm Hg decreased to 1.5 mm Hg after stenting (p<0.001). No intraprocedural complication or junctional SSS stenosis distal to the stent construct was noted. Improvement in headache, tinnitus, and visual obscurations was reported by 66.7%, 63.6%, and 50% of affected patients, respectively, at mean follow-up of 5.2 months. We divided the SSS into four anatomically equal segments, numbered S1-S4, from the torcula to frontal pole. SSS stenosis typically occurs in the S1 segment, and the anterior extent of SSS stents was deployed at the S1-S2 junction in all but one case., Conclusions: SSS stenting is reasonably safe, may improve clinical symptoms, and significantly reduces maximum MVP and trans-stenosis pressure gradients in patients with VOD with SSS stenosis. The S1 segment is most commonly stenotic, and minimum pressure gradients for symptomatic SSS stenosis may be lower than for transverse or sigmoid stenosis. Additional studies and follow-up are necessary to better elucidate appropriate clinical indications and long-term efficacy of SSS stenting., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly., Methods: A literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes., Results: Fifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (n = 3144) and 13 were endoscopic (n = 940). Three studies compared microsurgical (n = 111) to endoscopic TSR outcomes (n = 180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively., Conclusions: Both endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.

Purpose The relationship between syringomyelia and presyrinx, characterized by edema in the spinal cord, has not been firmly established. Patients with syringomyelia have abnormal spinal canal tapering that alters cerebrospinal fluid flow dynamics, but taper ratios in presyrinx have never been reported. We tested the hypothesis that presyrinx patients have abnormal spinal canal tapering. Materials and methods At six medical institutions, investigators searched the PACS system for patients with Chiari I and spinal cord edema unassociated with tumor, trauma, or other evident cause. In each case taper ratios were calculated for C1 to C4 and C4 to C7. In two age- and gender-matched control groups, Chiari I patients with no syringomyelia and patients with normal MR scans, the same measurements were made. Differences between groups were tested for statistical significance with t tests. Results The study enrolled 21 presyrinx patients and equal numbers of matched Chiari I and normal controls. C4 to C7 taper ratios were positive and steeper in presyrinx patients than in the normal controls ( p = 0.04). The upper cervical spine, C1 to C4, tapered negatively in cases and controls without significant differences between the groups. The difference in degree of tonsillar herniation was statistically significant between presyrinx patients and Chiari I controls ( p = 0.01). Conclusions Presyrinx patients have greater than normal positive tapering in the lower cervical spine and greater degree of tonsillar herniation than the controls.

Since the discovery of the non-image-forming visual system, tremendous research efforts have been dedicated to understanding its mechanisms and functional roles. Original functions associated with the melanopsin system include the photoentrainment of circadian sleep-wake cycles and the pupillary light reflex. Recent findings, however, suggest a much broader involvement of this system in an array of physiologic responses to light. This newfound insight into the underlying function of the non-image-forming system has revealed the many connections to human pathology and attendant disease states, including seasonal affective disorder, migraine, glaucoma, inherited mitochondrial optic neuropathy, and sleep dysregulation of aging. In this review, the authors discuss in detail the clinical implications of the melanopsin system., (© 2017 American Academy of Neurology.)

OBJECTIVE The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods. METHODS The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS). RESULTS The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test). CONCLUSIONS Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.

OBJECT Gamma Knife radiosurgery (GKRS) is frequently employed to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of radiographic progression of tumor. METHODS This is a retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS between 1996 and 2013 at the University of Virginia Health System. Patients were stratified based on the interval between resection and radiosurgery. Operative results and imaging and clinical outcomes were compared across groups following early (≤ 6 months) or late (> 6 months) radiosurgery. RESULTS Sixty-four patients met the study criteria and were grouped based on early (n = 32) or late (n = 32) GKRS following transsphenoidal resection. There was a greater risk of tumor progression after GKRS in the late radiosurgical group (p = 0.027) over a median radiographic follow-up period of 68.5 months. Furthermore, there was a significantly higher occurrence of post-GKRS endocrinopathy in the late radiosurgical cohort (p = 0.041). Seventeen percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 64% in the late cohort (p = 0.036). This difference was primarily due to a significantly higher rate of tumor growth during the observation period of the late treatment cohort (p = 0.014). Of these patients with completely new endocrinopathies, radiation-associated pituitary insufficiency developed in 1 of 2 patients in the early group and in 3 of 7 (42.9%) patients in the late group. CONCLUSIONS Early treatment with GKRS appears to decrease the rate of radiographic and symptomatic progression of subtotally resected nonfunctioning pituitary macroadenomas compared with late GKRS treatment after a period of expectant management. Delaying radiosurgery may place the patient at increased risk for adenoma progression and endocrinopathy.

OBJECTIVE Intraventricular hemorrhage (IVH) is a common complication of premature neonates with small birth weight, which often leads to hydrocephalus and treatment with ventriculoperitoneal (VP) shunting procedures. Trapped fourth ventricle (TFV) can be a devastating consequence of the subsequent occlusion of the cerebral aqueduct and foramina of Luschka and Magendie. METHODS The authors retrospectively reviewed 8 consecutive cases involving pediatric patients with TFV following VP shunting for IVH due to prematurity between 2003 and 2012. The patients ranged in gestational age from 23.0 to 32.0 weeks, with an average age at first shunting procedure of 6.1 weeks (range 3.1-12.7 weeks). Three patients were managed with surgery. Patients received long-term radiographic (mean 7.1 years; range 3.4-12.2 years) and clinical (mean 7.8 years; range 4.6-12.2 years) follow-up. RESULTS The frequency of TFV following VP shunting for neonatal posthemorrhagic hydrocephalus was found to be 15.4%. Three (37.5%) patients presented with symptoms of posterior fossa compression and were treated surgically. All of these patients showed signs of radiographic improvement with stable or improved clinical examinations during postoperative follow-up. Of the 5 patients treated conservatively, 80% experienced stable ventricular size and 1 patient experienced a slight increase (3 mm) on imaging. All of the nonsurgical patients showed stable to improved clinical examinations over the follow-up period. CONCLUSIONS The frequency of TFV among premature IVH patients is relatively high. Most patients with TFV are asymptomatic at presentation and can be managed without surgery. Symptomatic patients may be treated surgically for decompression of the fourth ventricle.

OBJECT The natural and surgical history of Chiari malformation Type I (CM-I) in pediatric patients is currently not well described. In this study the authors discuss the clinical and radiological presentation and outcomes in a large cohort of pediatric CM-I patients treated with either conservative or surgical management. METHODS The authors retrospectively reviewed 95 cases involving pediatric patients with CM-I who presented between 2004 and 2013. The patients ranged in age from 9 months to 18 years (mean 8 years) at presentation. The cohort was evenly split between the sexes. Twenty-five patients underwent posterior fossa decompression (PFD) with either dural splitting or duraplasty. Seventy patients were managed without surgery. Patients were followed radiologically (mean 44.8 months, range 1.2-196.6 months) and clinically (mean 66.3 months, range 1.2-106.5 months). RESULTS Seventy patients were treated conservatively and followed with serial outpatient neurological and radiological examinations, whereas 25 patients were treated with PFD. Of these 25 surgical patients, 11 were treated with duraplasty (complete dural opening) and 14 were treated with a dura-splitting technique (incomplete dural opening). Surgical intervention was associated with better clinical resolution of symptoms and radiological resolution of tonsillar ectopia and syringomyelia (p = 0.0392). Over the course of follow-up, 20 (41.7%) of 48 nonsurgical patients who were symptomatic at presentation experienced improvement in symptoms and 18 (75%) of 24 symptomatic surgical patients showed clinical improvement (p = 0.0117). There was no statistically significant difference in resolution of symptoms between duraplasty and dura-splitting techniques (p = 0.3572) or between patients who underwent tonsillectomy and tonsillopexy (p = 0.1667). Neither of the 2 patients in the conservative group with syrinx at presentation showed radiological evidence of resolution of the syrinx, whereas 14 (87.5%) of 16 patients treated with surgery showed improvement or complete resolution of syringomyelia (p = 0.0392). In the nonsurgical cohort, 3 patients (4.3%) developed new or increased syrinx. CONCLUSIONS The overwhelming majority of CM-I patients (92.9%) managed conservatively do not experience clinical or radiological progression, and a sizeable minority (41.7%) of those who present with symptoms improve. However, appropriately selected symptomatic patients (sleep apnea and dysphagia) and those presenting with syringomyelia should be considered surgical candidates because of the high rates of clinical (75%) and radiological improvement (87.5%).

Objective: Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer's disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided., Methods: The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups., Results: From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer's pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer's pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136)., Conclusions: A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer's pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evidence of AD pathology on repeat biopsy, demonstrating the progressive nature of the disease.

We present a rare extramedullary ependymoma with diffuse spinal metastatic disease, and review the previous reports of extramedullary spinal ependymomas. Ependymomas are the most common intramedullary spinal cord tumor in adults. These tumors rarely present as extramedullary masses. We treated a 23-year-old man with a history of progressive neck, shoulder and arm pain, with sensory and motor symptoms in the C7 dermatome. MRI of the cervical spine demonstrated a ventral contrast-enhancing lesion with evidence of enhancement along the dura and spinal cord of the upper cervical spine, thoracic spine, and cauda equina. He underwent a tumor debulking procedure without complications. Following surgery, he received craniospinal radiation to treat the remaining tumor and diffuse leptomeningeal disease. The final pathology of the tumor revealed that is was a World Health Organization Grade III anaplastic ependymoma. At the 1 year follow-up, the patient had stable imaging and had returned to his preoperative functional status. Of the 19 reported patients with primary intradural, extramedullary spinal ependymomas, two had extradural components and seven had anaplastic grades. Only one tumor with an anaplastic grade resulted in metastatic disease, but without spinal recurrence. To our knowledge, this is the first report of an intradural, extramedullary spinal ependymoma with an anaplastic grade, presenting with concomitant diffuse, nodular leptomeningeal metastasis involving the upper cervical spine, thoracic spine, conus medullaris, and cauda equina. Similar to the treatment of intramedullary ependymomas with metastasis, this patient underwent an aggressive debulking procedure followed by radiation therapy to the entire neuroaxis.

Sleep apnea represents a relative indication for posterior fossa decompression in pediatric patients with Chiari malformation type 1. Duraplasty was associated with improvement of sleep apnea in 100% of patients and dural splitting with improvement in 50% of patients. Duraplasty and dural splitting were associated with a similar reduction in tonsillar herniation on radiographic imaging of 58% (37% excluding tonsillectomy) and 35%, respectively. Longitudinal follow-up studies of patients with either neurologic deficits or severe symptoms will further elucidate the natural history of Chiari malformation type 1 and more appropriately gauge the risk-benefit tradeoff of surgical intervention., (Copyright © 2015 Elsevier Inc. All rights reserved.)