Long-term outcome of primary clival chordomas: a single-center retrospective study with an emphasis on the timing of recurrences based on the primary treatment.

OBJECTIVE: This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). RESULTS: The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38-132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24-70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16-97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26-86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5-62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. CONCLUSIONS: In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

Precision oncology in neurofibromatosis type 1: quantification of differential sensitivity to selumetinib in plexiform neurofibromas using single-cell RNA sequencing.

PURPOSE: Selumetinib is an FDA-approved targeted therapy for plexiform neurofibromas in neurofibromatosis type 1(NF1) with durable response rates seen in most, but not all patients. In this proof-of-concept study, we demonstrate single-cell RNA sequencing(scRNAseq) as a technique for quantifying drug response to selumetinib at the single cell level. METHODS: scRNAseq data from neurofibroma biopsies was obtained from a public genomics repository. Schwann cell populations were identified through standard clustering techniques and single-cell selumetinib sensitivity was quantified on a scale of 0(resistant) to 1(sensitive) based on the expression pattern of a 500 gene selumetinib sensitivity signature from the BeyondCell sensitivity library. RESULTS: A total of seven plexiform neurofibromas were included in our final analysis. The median absolute number of Schwann cells across samples was 658 cells (IQR: 1,029 cells, Q1-Q3: 135 cells to 1,163 cells). There was a statistically significant difference in selumetinib sensitivity profiles across samples (p < 0.001). The tumor with the highest median selumetinib sensitivity score had a median selumetinib sensitivity score of 0.64(IQR: 0.14, Q1-Q3: 0.59-0.70, n = 112 cells) and the tumor with the lowest median selumetinib sensitivity score had a median score of 0.37 (IQR: 0.21, Q1-Q3: 0.27-0.48, n = 1,034 cells). CONCLUSIONS: scRNAseq of plexiform neurofibroma biopsies reveals differential susceptibilities to selumetinib on a single cell level. These findings may explain the partial responses seen in clinical trials of selumetinib for NF1 and demonstrate the value of collecting scRNAseq data for future NF1 trials.

A Case of Long-Term Survival After Glioblastoma, IDH-Wild Type.

INTRODUCTION: Glioblastoma is a uniformly lethal primary central nervous system neoplasm. Despite the increased understanding of its pathophysiology and treatment advancements, median overall survival for patients with glioblastoma, IDH-wild type remains 14 to 21 months from diagnosis. CASE REPORT: We present the case of a 48-year-old female who presented with a focal seizure and was found to have a right frontal lobe mass on the brain magnetic resonance imaging. She underwent gross total resection and received a histological diagnosis of glioblastoma. She received radiotherapy and 6 cycles of carmustine (BCNU). Seventeen months later, she developed left hemiparesis. Imaging was concerning for tumor progression, and she was treated with 1 cycle of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone (MOPP). Subsequent surveillance imaging demonstrated a therapeutic response. Twenty-seven years after her glioblastoma diagnosis, she developed status epilepticus and died from respiratory failure. Neuropathology on autopsy demonstrated extensive treatment-related changes but no evidence of recurrent glioblastoma. Genomic testing performed over 30 years after her original diagnosis revealed a profile diagnostic of glioblastoma, IDH-wild type per 2021 World Health Organization criteria. CONCLUSIONS: This patient is one of the longest-known survivors of glioblastoma, IDH-wild type, with pathologic confirmation of glioblastoma at the time of her resection and no evidence of residual disease 26 years after her last treatment. She presented with multiple factors associated with long-term glioblastoma survivorship, including female sex, young age, high Karnofsky score, and multimodal therapy. This case shows that long-term survival after glioblastoma diagnosis is possible and likely mediated through a combination of individual, tumor, and treatment factors.

Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study.

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA). We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays. The cohort was comprised of 8 females and males, each, with an age range of 33-79 years (median, 59), and a tumor size range of 3.4-15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally. Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC. MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Patterns of recurrence and disease progression in patients with positive-margin olfactory neuroblastoma following primary resection.

OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. METHODS: The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19-70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38-72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45-164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03-78.86, p = 0.007; HR 7.31, 95% CI 1.45-36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. CONCLUSIONS: Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.

Capillary Hemangioma of the Spinal Cord: Case Report and Systematic Review of Literature.

BACKGROUND: Capillary hemangiomas are rare vascular lesions that rarely affect the central nervous system. When they present within the spinal canal, they are typically confined intradurally, with intramedullary extension rare. We present a rare case of spinal intramedullary capillary hemangioma, with a systematic review of the literature. METHODS: Medical records and imaging data were retrospectively reviewed using the health record software EPIC (Verona, Wisconsin, USA) and the radiology management software system RIS/PACS (Radiology Information System/Picture Archiving and Communication System; QREADS). The report was written in accordance with the CARE (case reports) guidelines. We also performed a systematic review of the literature on all cases of intramedullary spinal capillary hemangiomas in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. RESULTS: We report a case of a 54-year-old man who presented with progressive paraplegia and sensory deficits in the lower extremities. Spinal magnetic resonance imaging showed an intramedullary enhancing lesion centered at T11 with associated spinal cord compression. He underwent thoracic laminectomy and gross total resection of the lesion without complications and subsequent improvement on his neurological examination. Histological examination showed findings consistent with a capillary hemangioma. The literature review also documented 21 studies with a combined total of 38 cases of intramedullary spinal capillary hemangioma. CONCLUSIONS: Purely intramedullary capillary hemangiomas are unusual spinal lesions with only a few cases reported in the literature. These should be considered in the differential diagnosis of intramedullary tumors. Surgical management remains the first line of treatment for symptomatic patients.

Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.

Segmental extraneural lipomatosis of the superficial peroneal nerve: illustrative case.

BACKGROUND: Adipose lesions of nerve are rare tumors that can cause nerve symptoms from either intrinsic or extrinsic compression. OBSERVATIONS: The authors present a case of a patient with a 10-year history of progressive, persistent leg pain and dorsal foot paresthesias/dysesthesias. Imaging revealed several nondistinct nodules of indeterminate significance along the course of the superficial peroneal nerve (SPN). Surgery demonstrated six distinct extraneural lipomas studded on a 10-cm segment of the main SPN and one of its muscular branches in the midleg. The lesions were adherent to the SPN, without an easy dissection plane; therefore, a neurectomy was performed. Histology revealed the nerve was associated with multiple extraneural lipomas with focal evidence of prior trauma. At 4 months postoperatively, the patient's pain had resolved completely, and she was able to resume normal physical activities. LESSONS: The current classification of adipose lesions of nerve includes intraneural and extraneural lipomas and lipomatosis of nerve (fibrolipomatous hamartoma). The unique features of the present case include the discrete and segmental nature of the extraneural lipomas adherent to the nerve. Its etiology is unknown, and the histology would be suggestive of either a traumatic or a degenerative process.

BRAT1-Associated Leukodystrophy Exacerbated by Classic Hodgkin Lymphoma-Directed Therapy.

INTRODUCTION: BRCA1-associated ataxia-telangiectasia-mutated activator-1 (BRAT1) is responsible for cell cycle surveillance and mitochondrial function. The implications of adult-onset BRAT1-variant and the resulting phenotypic neurocognitive and imaging features have not been previously described. CASE REPORT: A 66-year-old man with a recent diagnosis of classic Hodgkin lymphoma was referred to neuro-oncology for cognitive and motor decline, and progressive cerebral white matter changes noted on magnetic resonance imaging (MRI). A neurological examination revealed global weakness, broad-based gait, and bilateral extensor plantar responses. Brain MRI demonstrated periventricular, deep, and subcortical white matter T2/FLAIR hyperintensities without contrast enhancement. Cerebral spinal fluid studies were unremarkable. A GeneDX genetic leukodystrophy panel conduction revealed a pathogenic variant (c.294dupA; p.L99TfsX92) resulting in a truncated protein of BRAT1, along with a variant of uncertain significance (c.746A>G;p.E249G). A presumptive diagnosis of late-onset leukoencephalopathy secondary to the BRAT1 variant was made. In an attempt to combat his mitochondrial dysfunction, he was initiated on a mitochondrial cocktail, including B-100 complex and coenzyme Q10. He began lymphoma-directed combination chemotherapy and developed precipitous functional decline after 2 cycles of therapy. Compared with prechemotherapy imaging, repeat positron emission tomography/computed tomography metabolic imaging showed a response after 3 cycles of chemotherapy; however, repeat brain MRI showed worsening diffuse white matter hyperintensities and cerebral atrophy. CONCLUSION: Given the variability in phenotypes and clinical onset, leukodystrophies can be a diagnostic challenge. This case demonstrated progressive BRAT1-associated leukodystrophy exacerbated by chemotherapy-induced toxic leukoencephalopathy. Mitochondrial energy deficiency in the context of multiple metabolic insults was likely underlying the progressive neurological decline observed in this case of genetic leukodystrophy.

Calcifying Pseudoneoplasm of the Neuraxis: An Institutional Series of Ten Cases and Review of the Literature to Date.

BACKGROUND: Calcified pseudoneoplasms of the neuraxis (CAPNONs) are rare, fibro-osseous lesions with an unknown cause that may present anywhere along the neuroaxis. Little is known about how intracranial CAPNONs present and about patients' long-term outcomes. METHODS: A retrospective institutional review of intracranial pathology-confirmed CAPNONs was performed. Presenting clinical features, management, and clinical outcomes are highlighted. A literature review of intracranial CAPNON lesions was also performed to build on our series. RESULTS: Ten patients were identified who met the inclusion criteria. Most patients presented with headaches (n = 6; 60%), seizures (n = 5; 50.0%), and neck and facial pain (n = 3; 30.0%). Most lesions were supratentorial (n = 7; 70.0%), with 3 infratentorial origins. Surgical resection was the most common initial management undertaken (n = 7; 70.0%). No new permanent postoperative neurologic deficits were identified. The median clinical and/or radiographic follow-up for all patients was 6.8 years (range, 0.7-23.3 years), with no recurrence of disease for 5 patients who underwent gross total resection. Four of 5 patients with residual or nonresectable lesions showed no interval growth on radiographic follow-up; 1 patient showed progression and worsening of presenting symptoms 2 months after resection. Resection substantially improved seizures and headaches in patients presenting with these symptoms (80% and 83.3%, respectively). CONCLUSIONS: Intracranial CAPNONs may present with a wide variety of symptoms characteristic of the site of origin. The outcomes of these symptoms regarding survival and disease control are generally favorable, although resection does not always yield complete resolution of presenting deficits in certain patients, particularly those presenting with headaches or neck/facial pain.

Surgical resection of recurrent intramedullary subependymoma of the cervical spinal cord.

Spinal subependymomas (SE) are rare, often indolent benign tumors presenting most frequently as intramedullary tumors in the cervical spine or cervicothoracic junction. When symptomatic, patients often present with years of sensory changes, weakness, paresthesias, or bowel and bladder dysfunction. Preoperatively, SE are difficult to distinguish radiographically from ependymomas or astrocytomas; however, it is important to make the distinction intraoperatively as complete resection can be curative. Here the authors present a rare case of recurrent, symptomatic cervical subependymoma which underwent gross-total resection and discussion of management strategies and outcomes of all SE at their institution.

Histopathology of Meningiomas.

Meningiomas are considered to arise from meningothelial cells, whose cytomorphology they recapitulate. In this chapter, we review the characteristic histological features of meningioma, including classic architectural and cytological features. There exists a broad spectrum of morphological variants of meningioma. The 2021 WHO Classification recognizes nine benign (grade 1), three intermediate-grade (grade 2), and three malignant (grade 3) variants. We review the characteristic histological features of these meningioma variants, describe immunohistochemical stains, which may assist with establishing a diagnosis, and discuss differential diagnostic considerations that may prove challenging for a diagnosis of meningioma.

Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood. METHODS: We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses. RESULTS: We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses. DISCUSSION: We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).

Genomic markers of recurrence risk in atypical meningioma following gross total resection.

Background: Meningiomas are the most common primary central nervous system (CNS) tumor in adults and CNS World Health Organization grade 2 (atypical) meningiomas show an intermediate risk of recurrence/progression. Molecular parameters are needed to better inform management following gross total resection (GTR). Methods: We performed comprehensive genomic analysis of tumor tissue from 63 patients who underwent radiologically confirmed GTR of a primary grade 2 meningioma, including a CLIA-certified target next-generation sequencing panel (n = 61), chromosomal microarray (n = 63), genome-wide methylation profiling (n = 62), H3K27me3 immunohistochemistry (n = 62), and RNA-sequencing (n = 19). Genomic features were correlated with long-term clinical outcomes (median follow-up: 10 years) using Cox proportional hazards regression modeling and published molecular prognostic signatures were evaluated. Results: The presence of specific copy number variants (CNVs), including -1p, -10q, -7p, and -4p, was the strongest predictor of decreased recurrence-free survival (RFS) within our cohort (P < .05). NF2 mutations were frequent (51%) but did not show a significant association with RFS. DNA methylation-based classification assigned tumors to DKFZ Heidelberg benign (52%) or intermediate (47%) meningioma subclasses and was not associated with RFS. H3K27 trimethylation (H3K27me3) was unequivocally lost in 4 tumors, insufficient for RFS analysis. Application of published integrated histologic/molecular grading systems did not improve prediction of recurrence risk over the presence of -1p or -10q alone. Conclusions: CNVs are strong predictors of RFS in grade 2 meningiomas following GTR. Our study supports incorporation of CNV profiling into clinical evaluation to better guide postoperative patient management, which can be readily implemented using existing, clinically validated technologies.

Unrecognized notochordal lesions as a likely cause of idiopathic clival cerebrospinal fluid leaks.

OBJECTIVE: To examine an association between idiopathic transclival cerebrospinal fluid (CSF) leak and notochordal lesions. METHODS: This study consisted of the illustrations of institutional patients who underwent surgery for transclival CSF leak between January 1, 2009 and April 25, 2020 and comprehensive review of the existing literature conducted on April 25, 2020. The cases were classified based on the presumed etiologies that were originally proposed in the articles ("idiopathic" vs. "secondary"). The baseline characteristics were compared between the groups, and the surgical outcomes were summarized. RESULTS: In 3 institutional cases, ecchordosis physaliphora (EP) was confirmed at the fistula either pathologically (1) or radiologically (2). Among 42 literature cases, 28 were recognized as idiopathic, while 14 were secondary cases with histologically (n = 12) or radiologically (n = 2) confirmed notochordal lesion at the fistula. Thus, any notochordal lesions were histologically confirmed in 13 among a total of 45 cases (28.9%). Fourteen of the idiopathic cases had undescribed radiographic signs suggestive of small ecchordosis physaliphora at the fistula. Both idiopathic and secondary cases demonstrated resemblance in their ages (mean, 51.4 and 56.6 years; p = 0.102), female predominance (male, 36% vs. 25%; P = 0.521), no association with obesity (7% vs. 18%; P = 0.350) or increased intracranial pressure (7% vs. 6%; P = 1.000). All the fistulas were in the midline or paramidline clivus within several millimeters below the dorsum sellae. All the patients were treated surgically with a multilayer closure, resulting in a success rate of 93% with one surgery. CONCLUSION: Our analyses suggest the association of transclival CSF leak and notochord lesions. A prospective study is needed for definitive conclusion.