Pediatric Spinal Vascular Abnormalities: Overview, Diagnosis, and Management.

Hemangioblastomas are true benign vascular neoplasms arising from pluripotent mesenchymal stem cells that give rise to vascular endothelial cells and are most commonly found in the cerebellum, spinal cord, brainstem, and retina. These tumors may be isolated sporadic lesions or may be associated with hereditary genetic factors in the case of von Hippel-Lindau (VHL) syndrome. Spinal cord haemangioblastomas constitute 1.1% to 2.4% of all central nervous system tumors105, with the majority being single tumors that present in the fourth decade of life 106. In the pediatric population, sporadic spinal cord hemangioblastomas are exceedingly rare. The prevalence of spinal cord hemangioblastomas in children is increased among those with VHL syndrome. The thoracic cord is the most common site for spinal cord hemangioblastomas, followed by the cervical cord. Although these tumors are benign, they cause disabling symptoms due to spinal cord compression, syringomyelia, or hemorrhage from the tumor itself or from aneurysms that form on tumor-feeding arteries or intra-tumoral vessels.

Consensus guidelines for the management of posterior fossa tumour for low- and middle-income countries.

The posterior fossa is a limited compartment therefore lesions compressing its structures can result in devastating outcomes. It can cause significant neurological deficit due to mass effect on critical structures and hydrocephalus. Due to the nature of the infratentorial region, urgent surgical intervention is often the first-line option. Surgical neuro-oncologists guide patients and caregivers through the course of this disease and to inform them about the various options for management and long-term outcome optimisation. There is currently conflicting data; however, institutional experiences can guide us towards achieving improvements in surgical outcomes and quality of life. Advances in molecular classifications coupled with highdose radiation treatment improve our capacity for improving overall survival in these patients. Common childhood tumours are ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, while adults often present with metastases, and less commonly, cerebellar haemangioblastomas and gliomas. This paper outlines management strategies with consideration for multidisciplinary care and resourcelimited settings.

Pediatric intramedullary spinal cord tumors: A national cancer database analysis of demographics, patterns of care, and survival.

OBJECTIVE: Query the National Cancer Database (NCDB) to delineate epidemiologic frequency, care patterns, and survival outcomes of pediatric intramedullary spinal cord tumors (IMSCTs). METHODS: IMSCTs included ependymoma, astrocytoma, and hemangioblastoma. We examined data from the NCDB spanning 2004-2018, focusing on IMSCT in children aged 0-21 years. Our analysis included logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models. RESULTS: This study included 1066 patients aged 0-21 years. 59.4 % of patients were male, while 83.1 % were white. The most common tumor histology was ependymoma (57.5 %), followed by astrocytoma (36.1 %) and hemangioblastoma (6.4 %). 24.9 % of patients received radiotherapy, with radiotherapy utilization being highest among patients aged 6-10 years. Chemotherapy utilization was highest in patients aged 0-5 years. 87.2 % of patients underwent surgical resection, with higher rates in patients aged 16-21 years. Overall survival did not differ significantly between resected and non-resected patients (p = 0.315). Patients in rural areas had worse OS than those in metro areas (HR = 4.42, p = 0.048). Patients with astrocytoma had worse OS compared to other histologies (HR = 2.21, p = 0.003). Astrocytoma patients were over twice as likely to have prolonged LOS compared to ependymoma patients (OR = 2.204, p < 0.001). CONCLUSIONS: In summary, our analysis utilizing the NCDB database provides a comprehensive overview of demographics, care patterns, and outcomes for the largest cohort of pediatric IMSCTs to date. These insights underscore the complexity of managing IMSCTs and emphasize the need for tailored approaches to improve patient outcomes.

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

PURPOSE: To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). METHODS: A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). RESULTS: Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). CONCLUSION: Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.

Assessing the efficacy and safety of hemangioblastoma embolization: A comprehensive systematic review and meta-analysis.

BACKGROUND: Hemangioblastomas (HBs) are highly vascular tumors linked to substantial morbidity and mortality. Recently, interventional neuroradiology has evolved rapidly, spurring interest in preoperative embolization as a possible HB treatment. PURPOSE: This study evaluates the effectiveness and safety of preoperative embolization in managing HB. METHODS: Adhering to PRISMA guidelines, this meta-analysis considered randomized and nonrandomized studies meeting specific criteria, encompassing intracranial HB and preoperative embolization. Primary outcomes were preoperative embolization efficacy and safety. Complications were classified as major (cerebellar ischemia, ischemic strokes, intratumoral hemorrhage, subarachnoid hemorrhage) and minor (transient nystagmus, slight facial nerve palsy, nausea, transient dysarthria, hemiparesis, hemisensory impairment, thrombotic complications, extravasation). RESULTS: Thirteen studies involving 166 patients with preoperative embolization before HB resection were included. Two studies using the Glasgow Outcome Scale (GOS) showed 5 patients with good recovery, 6 with moderate disability, and 3 with severe disability. Major complications occurred in 1% (95% CI: 0% to 3%), and minor complications occurred in 1% (95% CI: 0% to 4%). Intraoperative blood loss during resection was estimated at 464.29 ml (95% CI: 350.63 ml to 614.80 ml). CONCLUSION: Preoperative embolization holds promise in reducing intraoperative bleeding risk in neurosurgical intracranial HB treatment, primarily due to its low complication rates. Nonetheless, additional research and larger-scale studies are essential to establish its long-term efficacy and safety. These findings highlight preoperative embolization as a valuable tool for HB management, potentially enhancing future patient outcomes.

von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance.

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. RECOMMENDATIONS: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

Efficacy and safety of current treatment options for peripheral retinal haemangioblastomas: a systematic review.

IMPORTANCE: Approximately twenty per cent of Von Hippel-Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available for peripheral RH. However, management of peripheral RH is complex due to multifocality and bilaterality. OBJECTIVE: To summarize published evidence on efficacy and safety of different interventions for peripheral RH and to provide treatment recommendations for specialists. EVIDENCE REVIEW: Comprehensive searches were performed using Medline, Embase, Web of Science and Google Scholar database on 4 March 2020. English publications that described outcomes related to efficacy or complications in at least two patients with peripheral RH were included. Efficacy and safety were estimated by complete tumour eradication rate, pretherapeutic and treatment-related complication rate. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to calculate the risk estimate of complications between treatment options. FINDINGS: Twenty-seven articles were included in this review describing nine different treatment options for peripheral RH: laser photocoagulation (n = 230), cryotherapy (n = 50), plaque radiotherapy (n = 27), vitreoretinal surgery (n = 88), photodynamic therapy (PDT; n = 14), transpupillary thermotherapy (TTT; n = 10), external beam radiotherapy (n = 3), systemic treatment (n = 7) and intravitreal anti-VEGF (n = 2). Complete tumour eradication was achieved in 86.7% (95% CI: 83.5-89.9%) of all eyes. For the different treatments, this was after laser photocoagulation 89.9% (86.1-93.7%), cryotherapy 70.2% (57.0-83.4%), plaque radiotherapy 96.3% (89.1-100.0%), vitreoretinal surgery (100.0%), PDT 64.3% (38.3-90.3%) and TTT 80.0% (53.8-100.0%). No complete tumour eradication was achieved after systemic therapy, external beam radiotherapy or intravitreal anti-VEGF. Photodynamic therapy and vitreoretinal surgery showed the highest complication rate after treatment compared to the other treatments (OR 10.5 [95% CI: 2.9-38.4]) and (OR 5.9 [95% CI: 3.4-9.9]), respectively. Cases that had pretherapeutic complications showed a higher treatment-related complication rate (OR 14.8 [95% CI: 7.3-30.0]) than cases without complications before treatment. CONCLUSIONS AND RELEVANCE: These findings suggest that laser photocoagulation is the safest and most effective treatment method for peripheral RH up to 1.5 mm in diameter. Vitreoretinal surgery has the highest success rate for complete tumour eradication and may be the most suitable treatment option in the presence of pretherapeutic complications and for larger tumours.

Aggressive-fungating retinal hemangioblastoma.

Retinal hemangioblastomas are one of the most common and early manifestations of Von Hippel-Lindau disease. Early detection is the key in their management. When left untreated, these benign neoplasms may continue to grow and result in scleral infiltration and extraocular extension warranting enucleation of the globe.

Multimodal Imaging in the Diagnosis of Exophytic Juxtapapillary Retinal Capillary Hemangioblastoma.

PURPOSE: Exophytic juxtapapillary retinal capillary hemangioblastoma (JRCH) can be difficult to diagnose. We explore the value of multimodal imaging to aid in the diagnosis. DESIGN: Retrospective case series. METHODS: Medical records and multimodal imaging studies were reviewed on all patients diagnosed with RCH at Bascom Palmer Eye Institute, Miami, Florida, between January 2013 and December 2019. Patients with exophytic lesions within 2 mm of the disc were included. One patient from the Baylor College of Medicine, Houston, Texas was included. Patient demographics, referring diagnosis, history of von Hippel-Lindau syndrome, initial and last visual acuity, and treatments were recorded. Fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), OCT angiography, and B-scan images were reviewed. RESULTS: Twelve patients were identified with exophytic JRCH. The mean age was 54 years (range 38-73 years). Five patients had von Hippel-Lindau syndrome. The most common referral diagnoses were choroidal neovascularization and neuroretinitis. Imaging features included nodular outer retinal thickening with shadowing and intra-/subretinal fluid on OCT, hypoautofluorescence on fundus autofluorescence, middle to outer retinal hypervascularity on OCT angiography, early hyperfluorescence with late leakage on fluorescein angiography, and lack of choroidal vascular lesion on indocyanine green angiography. Treatments included photodynamic therapy (6 patients), intravitreal anti-vascular endothelial growth factor therapy (6 patients), argon laser photocoagulation (2 patients), intravitreal or sub-Tenon's triamcinolone (3 patients), and observation (4 patients). CONCLUSIONS: A key to the accurate diagnosis of exophytic JRCH is its intraretinal location, typically involving the outer retinal layers, which results in a clinical appearance that is distinct from the more common and easily recognizable endophytic RCH. Multimodal imaging can aid in ruling out choroidal neovascularization and disc edema by demonstrating an absence of involvement of those structures.

Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination.

Dissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2 years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In addition, the methylation class determined by the methylation profiling classifier developed by the German Cancer Research Center (DKFZ)/University Hospital Heidelberg/German Consortium for Translational Cancer Research was consistent with that of common hemangioblastomas. However, genetic analyses showed significant gains and losses throughout the whole genome, indicating that highly aberrant copy number profiles may be the key to elucidating this rare but life-threatening clinical entity. Accumulation of more detailed case reports based on the comparison of specimens obtained before and after surgery or radiation is necessary to better understand the pathophysiology of the dissemination phenotype of hemangioblastoma.

Intermixed arteriovenous malformation and hemangioblastoma: case report and literature review.

We report the third presentation of an intermixed arteriovenous malformation and hemangioblastoma. The rare occurrence of the diagnostic histologic features of both a neoplasm and vascular malformation in a single lesion is more common in gliomas, as angioglioma, and is termed an 'intermixed' lesion. We review the literature concerning the developmental biology of each lesion, and potential interplay in the formation of an intermixed vascular neoplasm and vascular malformation. The roles of cellular origin, genetic susceptibility, favourable microenvironment, altered local gene expression and key regulatory pathways are reviewed. Our review supports angiography and genetic profiling in intermixed lesions to inform management strategies. Consideration should be given to multimodality therapeutic interventions as required, including microsurgical resection, stereotactic radiosurgery and further research to exploit emerging molecular targets.

A solitary hemangioblastoma of the posterior brain fossa: the role of radiotherapy.

We report here the case of a patient admitted for management of posterior fossa cerebral hemangioblastoma. A 16-year-old male patient with a history of intracranial hypertension syndrome consisting of progressively worsening headache, vomiting, especially morning and jet vomiting, and decreased visual acuity. The patient's symptomatology worsened a few days later with the appearance of a disturbance of balance with enlargement of the sustentation polygon. The patient initially benefited from a brain computed tomography (CT) scan that objectified a solidocystic process of the posterior brain fossa. The patient then underwent a surgical excision that was considered partial and the diagnosis of hemangioblastoma was made on the surgical specimen. Since the surgical removal was partial the patient was referred to our training where he received external radiotherapy on his hemangioblastoma of the posterior brain fossa. The patient was examined one month after the end of irradiation; he presented a spectacular improvement in his neurological symptomatology with a clear regression of balance disorders. The standard treatment for cerebellar hemangioblastoma is complete microsurgical removal, but our results show a high level of efficacy for fractional photon radiotherapy after partial surgery of this benign tumour.

MANAGEMENT OF RETINAL HEMANGIOBLASTOMA IN VON HIPPEL-LINDAU DISEASE.

PURPOSE: To review the current state of diagnosis and management of retinal hemangioblastoma and retinal vascular proliferation arising from von Hippel-Lindau (VHL) disease. METHODS: A review of the literature was performed. Consensus was reached among authors regarding current practice, with reference to published data where possible. RESULTS: von Hippel-Lindau disease and its ocular manifestations are relatively rare, and there is limited evidence in the literature on which to base management. There was consensus on core principles, including 1) recognition and diagnosis of von Hippel-Lindau disease when present, with appropriate referral for care of this potentially lethal systemic condition; 2) regular ophthalmic evaluation for individuals with von Hippel-Lindau disease, to identify and offer timely treatment for new or active retinal hemangioblastomas; 3) ablative treatment of retinal hemangioblastomas that can be safely destroyed, to lower risk of vision loss; 4) observation or consideration of nonablative treatments for retinal hemangioblastomas that cannot be safely destroyed; and 5) observation of asymptomatic retinal vascular proliferation, with consideration of vitrectomy for lesions exerting effects on vision. CONCLUSION: Ocular outcomes can be gratifying in many cases with appropriate management. Improved understanding of the molecular basis for the disease creates an opportunity for rational design of better therapies.

Treatment Outcome of Intracranial Tumor Embolization in Japan: Japanese Registry of NeuroEndovascular Therapy 3 (JR-NET3).

Embolization for intracranial tumor is performed as a standard endovascular treatment. A retrospective, multicenter, observational study was conducted to clarify the nature, frequency, and risk factors of complications in intracranial tumor embolization. Patients were derived from the Japanese Registry of NeuroEndovascular Therapy (JR-NET3) using data taken from January 2010 through December 2014 in Japan. A total of 40,169 patients were enrolled in JR-NET3, of which, 1,545 patients (3.85%) with intracranial tumors underwent embolization. The primary end point was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 (independency) at 30 days after embolization. The secondary end point was the occurrence of complications related to the procedures. The risk factors of the development of complications were analyzed. The proportion of patients with mRS scores ≤2 at 30 days after procedure was 89.5%. Complications occurred in 57 of the 1544 patients (3.7%). Multivariate analysis showed that target vessels other than external carotid artery (ECA) (OR, 3.56; 95% CI, 2.03-6.25; P <0.001) and use of liquid material (OR, 2.65; 95% CI, 1.50-4.68; P <0.001) were significantly associated with the development of complications. In JR-NET3, the primary end point was 89.5%, and the procedure-related complication rate was 3.7%. Embolization from other than ECA was significant risk factor of the complications. In addition, increasing usage of liquid embolic material worsened the risk of complications.

Management and outcomes of pregnant patients with central nervous system hemangioblastoma.

The study aims to assess the management and maternal and fetal outcomes of pregnancies complicated by central nervous system (CNS) hemangioblastoma. Twenty-four female patients with CNS hemangioblastoma, who were pregnant in a tumor-burden status, were identified. Their medical charts, treatments, and follow-up materials were carefully reviewed. Of the included 24 CNS patients with hemangioblastoma (14 intracranial and 10 spinal hemangioblastomas), 5 patients (20.8%) were diagnosed with Von Hippel-Lindau disease (VHL). The median age of these patients at admission was 27.5 years. Intracranial hypertension was a common presenting symptom for patients with intracranial hemangioblastoma and was observed in 85.7% (12/14) of cases; the other 10 patients with spinal hemangioblastomas all suffered from paresthesia. Overall, 66.7% (16/24) of patients with CNS hemangioblastoma went through the gestational course with conventional observation; 16.6% (4/24) of patients accepted a ventriculo-peritoneal shunt (VPS) to delay the tumor resection; and 16.7% (4/24) of patients needed urgent tumor resection even when symptomatic treatments were given. Variable symptom improvement was seen when patients had follow-up visits at a median of 32.5 months. No maternal death or tumor recurrence was identified. For the fetal prognoses, one (4.2%) pregnancy ended in a spontaneous miscarriage and for (16.7%) pregnancies were interrupted; the other 19 (79.2%) live births were in good status without any congenital malformations. Symptomatic treatment was the first choice for pregnant patients with CNS hemangioblastoma. When needed, urgent tumor resection could be safely achieved with careful maternal and fetal monitoring. Both maternal and fetal prognoses were favorable during follow-up.

Assessment of care pattern and outcome in hemangioblastoma.

Due to its rarity, current literature assessing prognostic factors and survival outcomes of hemangioblastoma is limited. Patients with histologically confirmed hemangioblastoma were identified from the US National Cancer Data Base. 1488 patients met inclusion criteria. 644 patients underwent gross total resection (GTR), 220 subtotal resection (STR)/biopsy, 60 stereotactic radiosurgery (SRS), 15 external beam radiotherapy (EBRT), 51 surgery followed by radiotherapy (SR + RT) and 498 no treatment. Independent predictors of shorter OS included age ≥ 40 (HR, 3.897; 95% CI, 2.341-6.487; p < 0.001), Charlson-Deyo score ≥ 1(HR, 1.756; 95% CI, 1.213-2.544; p = 0.003), tumor location in the brainstem (HR, 1.955; 95% CI, 1.129-3. 384; p = 0.017) compared to cerebellum, no treatment (HR, 2530; 95% CI, 1.533-4.177; p < 0.001) and receipt of EBRT (HR, 2.860; 95% CI, 1.073-7.618; p = 0.036) compared to STR/biopsy. GTR was associated with longer OS (HR 0.617; 95% CI, 0.391-0.974; p = 0.038), while SRS had comparable OS to STR/biopsy. The overall trend of OS by treatment modality was consistent after matching to age- and sex-matched US population data. In patients younger than 40 years, treatment was not a significant predictor of OS. In conclusion, GTR remained the optimal treatment for hemangioblastoma. SRS may perform similarly to surgery alone. Treatment was not a significant predictor of survival in younger patients.

[Retinal hemangioblastoma: Treatment strategy and long-term follow-up in a retrospective cohort]. / Hémangioblastomes rétiniens : stratégie thérapeutique et suivi à long terme dans une cohorte rétrospective.

INTRODUCTION: Retinal hemangioblastoma (RH) is a benign vascular tumor frequently associated with Von Hippel-Lindau disease (VHL). Tumor growth of RH may lead to deterioration of visual acuity, which can be difficult to treat. Early diagnosis may reduce complication rate and side effects of treatment. The present retrospective study evaluates the long-term follow-up and complications of RH treatment as a function of the therapeutic strategy used. MATERIALS AND METHODS: The study included patients with RH, followed at Croix Rousse university hospital, Lyon between 2010 and 2017. The following clinical features were recorded : age at diagnosis, presenting symptom, presence of VHL disease, treatments used, post-therapeutic complications and visual outcomes. RESULTS: Seven eyes of five patients were included in our study. Eighty percent of the patients had a mutation in the VHL gene. Four eyes (57%) were treated with laser photocoagulation and three eyes (43%) were treated with cryotherapy. The mean duration of follow-up was 35 months. One of the eyes treated using laser photocoagulation was complicated by an early epiretinal membrane with no visual consequence. Of the eyes treated by cryoapplication, one was complicated by a vitreous hemorrhage, and another by a rhegmatogenous retinal detachment, both of which resulted in a decrease in visual acuity. CONCLUSION: The long-term outcome for patients treated for RH was relatively good. Complications were strongly correlated with the initial size of the vascular tumor. Early diagnosis seems to improve visual outcomes. Ophthalmologic monitoring should be part of the systemic, multidisciplinary management.

The HIF and other quandaries in VHL disease.

Mutations in VHL underlie von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome with several subtypes depending on the risk of developing certain combination of classic features, such as clear cell renal cell carcinoma (ccRCC), hemangioblastoma and pheochromocytoma. Although numerous potential substrates and functions of pVHL have been described over the past decade, the best-defined role of pVHL has remained as the negative regulator of the heterodimeric hypoxia-inducible factor (HIF) transcription factor via the oxygen-dependent ubiquitin-mediated degradation of HIF-α subunit. Despite the seminal discoveries that led to the molecular elucidation of the mammalian oxygen-sensing VHL-HIF axis, which have provided several rational therapies, the mechanisms underlying the complex genotype-phenotype correlation in VHL disease are unclear. This review will discuss and highlight the studies that have provided interesting insights as well as uncertainties to the underlying mechanisms governing VHL disease.

Functional Outcome After Resection of Von Hippel-Lindau Disease-Associated Cauda Equina Hemangioblastomas: An Observational Cohort Study.

BACKGROUND: Cauda equina hemangioblastomas in von Hippel-Lindau (VHL) disease can cause significant neurological signs and symptoms. Despite their associated morbidity, the management of these tumors remains incompletely defined. OBJECTIVE: To determine optimal management, we analyzed the functional outcomes after resection of these tumors. METHODS: VHL patients who underwent surgical resection of cauda equina hemangioblastomas at the National Institutes of Health and the University of Virginia were included. Clinical and radiological follow-up was performed at 6- to 12-month intervals after surgery. RESULTS: Fifteen patients underwent 18 operations for 21 cauda equina hemangioblastomas (median follow-up 5.9 years). Patients often presented with multiple symptoms, including pain (67%), numbness (50%), urinary complaints (33%), and weakness (11%). Median preoperative tumor volume was 1.2 cm 3 . Four tumors at 3 operations were not resected due to a motor nerve root origin. Gross total resection was achieved in 14 surgeries (93% of operations when resection was attempted). New mild (non-function limiting) neurological symptoms were noted after 11 operations (61%), which most often (64%) resolved within 2 weeks of surgery. At 6-month follow-up, 15 patients (83%) were stable, 2 (11%) were improved, and 1 (6%) was worse. Histological analysis revealed that all tumors originated from within the involved nerve fascicle. CONCLUSIONS: VHL-associated cauda equina hemangioblastomas have an intrafascicular origin and require interruption of the rootlet of origin for complete resection. Motor nerve root involvement may preclude complete resection but strategies including bony decompression and/or interruption of vascular supply may provide a therapeutic option. Nevertheless, most VHL patients with symptom-producing lesions improve with resection.