Spinal Dural Arteriovenous Fistula in a Young Male Associated with Craniospinal Leptomeningeal Spread of a Treated High-Grade Glioma.

Spinal dural arteriovenous fistulae (SDAVF) are most commonly idiopathic in origin but may occasionally be seen secondary to surgery, trauma, or inflammation. We report a case of 27-year-old male who came with features of a myelopathy. He was found to have an SDAVF associated with leptomeningeal spread (LMS) of a previously treated high-grade cerebral glioma. Hemorrhagic presentation of gliomas, as in this case, is due to upregulation of vascular endothelial growth factor, which has also been postulated to play a role in the development of SDAVFs. This may suggest a possible mechanism of induction of secondary SDAVFs associated with such tumors. While the coexistence of intracranial neoplasms with vascular malformations has been reported previously, this is the first case report of LMS of a high-grade glioma associated with an SDAVF.

Leptomeningeal dissemination as a first sign of progression in metastatic melanoma: a diagnostic lesson.

One of the most serious complications of advanced melanoma is the diffusion of cancer cells to the central nervous system. The diagnosis of leptomeningeal metastasis (LMM) is notoriously challenging and requires a combination of consistent MRI and cerebrospinal fluid (CSF) cytology. In ambiguous cases, mutations like BRAF V600E in CSF-cell-free (cf)DNA may help to clarify diagnosis of LMM. Here we present the case of a young woman who developed isolated LMM after the diagnosis of a node-positive primary melanoma with normal LDH. The CSF was negative for tumour cells by cytology but positive for cfDNA BRAF V600E mutation, thus allowing us to diagnose LMM. To our knowledge, this is the first case where CSF sampling for the detection of BRAF mutation was used to identify leptomeningeal disease in the presence of negative MRI and without involvement of any other distant sites.

[Diagnostic Value of Locally Produced Tumor Markers and Blood Brain Barrier
Integrity in Lung Cancer Patients with Leptomeningeal Metastasis].

BACKGROUND: Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM. METHODS: Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient. RESULTS: Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P<0.05). Finally, evaluating the CSF cytology, integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect. Moreover, intrathecal TM synthesis changes earlier than cytology. CONCLUSIONS: The evaluation of intrathecal TM synthesis and integrity of BBB are novel clinical diagnostic tools. In addition, serial measurement of intrathecal synthesized TM may play an important role in monitoring efficacy of lung cancer patients with LM, which is worthy of further promotion and clinical application.

Leptomeningeal Carcinomatosis: Molecular Landscape, Current Management, and Emerging Therapies.

Leptomeningeal carcinomatosis is a devastating consequence of late-stage cancer, and despite multimodal treatment, remains rapidly fatal. Definitive diagnosis requires identification of malignant cells in the cerebrospinal fluid (CSF), or frank disease on MRI. Therapy is generally palliative and consists primarily of radiotherapy and/or chemotherapy, which is administered intrathecally or systemically. Immunotherapies and novel experimental therapies have emerged as promising options for decreasing patient morbidity and mortality. In this review, the authors discuss a refined view of the molecular pathophysiology of leptomeningeal carcinomatosis, current approaches to disease management, and emerging therapies.

Seizure prevalence, contributing factors, and prognostic factors in patients with leptomeningeal disease.

BACKGROUND: To determine seizure prevalence and contributing factors in patients with leptomeningeal disease (LMD). METHODS: Authors performed a retrospective review of 79 consecutive patients with a diagnosis of LMD. Associations between categorical variables were assessed using Chi-Square tests or Fisher's Exact tests. Survival was plotted with Kaplan Meier curves. Variables with a log-rank p-value of <0.20 were entered into a Cox Proportional Hazard regression analysis. RESULTS: Seizure prevalence in those with and without brain metastases was 22%. Of those who seized, 65% were admitted for this at least once while only one patient required intubation. Primary malignancy, type or route of chemotherapy administration, form of radiation therapy (craniospinal, focal, or whole brain), surgical treatment, location of LMD, and number of brain metastases did not influence seizure development. Only 13% of patients who never had seizures were on a prophylactic AED (anti-epileptic drug). In patients who had brain metastasis, there was no significant difference in prevalence of seizure before versus after LMD diagnosis suggesting that LMD does not significantly increase the risk of seizure compared to brain metastasis alone. A multivariate analysis revealed that while males trended toward inferior survival, only performance status and treatment with systemic chemotherapy showed a significant association with survival. Median survival time of patients after LMD diagnosis was four months. CONCLUSION: The prevalence of seizure in LMD patients is 22%. There were no statistically significant predisposing factors to seizure development. ECOG and use of systemic chemotherapy were found to be significant prognostic factors.

UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts.

BACKGROUND: Group 3 tumors account for approximately 25-30% of medulloblastomas and have the worst prognosis. UAB30 is a novel synthetic rexinoid shown to have limited toxicities in humans and significant efficacy in the pediatric neuroectodermal tumor, neuroblastoma. We hypothesized that treatment with UAB30 would decrease tumorigenicity in medulloblastoma patient-derived xenografts (PDXs). METHODS: Three group 3 medulloblastoma PDXs (D341, D384 and D425) were utilized. Cell viability, proliferation, migration and invasion assays were performed after treatment with UAB30 or 13-cis-retinoic acid (RA). Cell cycle analysis was completed using flow cytometry. A flank model, a cerebellar model, and a model of leptomeningeal metastasis using human medulloblastoma PDX cells was used to assess the in vivo effects of UAB30 and RA. RESULTS: UAB30 treatment led to cell differentiation and decreased medulloblastoma PDX cell viability, proliferation, migration and invasion and G1 cell cycle arrest in all three PDXs similar to RA. UAB30 and RA treatment of mice bearing medulloblastoma PDX tumors resulted in a significant decrease in tumor growth and metastasis compared to vehicle treated animals. CONCLUSIONS: UAB30 decreased viability, proliferation, and motility in group 3 medulloblastoma PDX cells and significantly decreased tumor growth in vivo in a fashion similar to RA, suggesting that further investigations into the potential therapeutic application of UAB30 for medulloblastoma are warranted.

Ventriculolumbar perfusion chemotherapy with methotrexate for treating leptomeningeal carcinomatosis: a Phase II Study.

BACKGROUND: The efficacy of ventriculolumbar perfusion (VLP) chemotherapy with methotrexate (MTX) was evaluated for treatment of leptomeningeal carcinomatosis (LMC). METHODS: The primary outcome was the response rate of increased intracranial pressure (ICP), which was available for comparison from historical data on conventional intraventricular chemotherapy. Secondary endpoints were response rates of other LMC symptoms and overall survival of patients. Artificial cerebrospinal fluid (CSF) premixed with MTX was continuously perfused intraventricularly through a preinstalled intraventricular reservoir and drained via lumbar catheter for 72 hours. The VLP was repeated twice at 3-day intervals for each cycle. RESULTS: Forty-five of 65 patients had increased ICP, and 32 patients (71%) showed response after VLP chemotherapy, including 31 patients with normalization of ICP. Altered mentation improved in 7 of 21 patients (33%). Cauda equina symptoms responded in 5 of 27 patients (19%), including 4 patients who became ambulatory from a bedridden state. Median overall survival was 187 days, and the 1-year survival rate was 27%. All side effects, including nausea, vomiting, confusion, and sleep disturbance, were tolerable and transient except for two cases of CSF infection. CONCLUSION: VLP chemotherapy with MTX provided better control of increased ICP, improved symptom response, and prolonged survival at a cost of acceptable toxicity in patients with LMC.

Leptomeningeal carcinomatosis mimicking Creutzfeldt-Jakob disease: clinical features, laboratory tests, MRI images, EEG findings in an autopsy-proven case.

Leptomeningeal carcinomatosis (LC) refers to diffuse seeding of the leptomeninges by tumor metastases. The clinical presentation may differ and the diagnosis may be difficult especially when cancer has not yet been diagnosed. We report a case of LC, where the clinical picture and a specific change in cerebrospinal fluid suggested the diagnosis of a prion disease.

Newer avenues for the treatment of leptomeningeal carcinomatosis.

Leptomeningeal Carcinomatosis (LC) refers to diffuse seeding of the leptomeninges by tumor metastases and is a rare presentation of solid tumors, particularly breast cancer, lung cancer and malignant melanoma in adults and hematogenous malignancies and primitive neuroectodermal tumor (PNET) in children. Recently, the incidence of LC has been reported to be increasing due to a longer overall survival obtained in patients treated with novel antineoplastic agents. The usual clinical presentation is a multifocal involvement of the neuraxis, with headache and radicular pain being the most common initial symptoms. The most frequent signs are motor deficits, altered mental status and cranial nerve involvement. The treatment of LC remains controversial and no straightforward guidelines exist in the literature. It has a bad prognosis and inevitably fatal outcome despite aggressive therapy.

Neoplastic meningitis.Review of a clinical series.

INTRODUCTION: The increase in the ageing population in the last decades has led to an increased frequency of cancer-associated complications. Among these, neurological disorders stand out, as they appear in 10-30% of patients with systemic neoplasia. Neoplastic meningitis accounts for 4-15% of patients with solid tumours and it has a poor prognosis. The objective of this paper is to describe the clinical, imaging and prognostic characteristics as well as cerebrospinal fluid findings in a series of neoplastic meningitis. BACKGROUND AND DEVELOPMENT: We performed a retrospective review of all patients admitted to the Hospital Universitario of Gran Canaria Dr. Negrín with clinical suspicion of neoplastic meningitis between 1990 and 2008. We selected 37 patients with an average age ranging from 15 to 75 years old. A total of 81.8% of the cases in which a primary tumour was found were associated with solid tumours (24.2% were located in the breast, and 24.2% in the lung). The most frequent sign of cranial nerve dysfunction was dyplopia, which was observed in 32.4% of the cases. The average survival rate after diagnosis was 87.9 days (12.6 weeks). The cerebrospinal fluid cytology was positive in 46.4% of the cases. CONCLUSION: Neoplastic meningitis is a severe complication of both solid and haematological tumours. We stress the importance of maintaining a high level of suspicion to achieve early diagnosis, since the average survival probability for neoplastic meningitis patients is low.

Spinal low-grade neoplasm with leptomeningeal dissemination mimicking tuberculous meningitis in a child.

Spinal seeding of primary malignant intracranial tumors via CSF is common. However, this is rare in low-grade glial tumors. Cranial leptomeningeal metastasis of primary spinal cord low-grade gliomas at diagnosis or relapse is extremely rare. Leptomeningeal metastasis of spinal cord low-grade tumors may mimic tuberculous meningitis in children. A patient with primary spinal cord low-grade neoplasm mimicked tuberculous meningitis is presented. The patient successfully treated with chemoradiotherapy. At the end of 19-month follow-up, diffuse leptomeningeal infiltration and a dural mass compatible with relapse developed. Chemoradiotherapy was started.

Leptomeningeal dissemination of a pediatric neoplasm with 1p19q deletion showing mixed immunohistochemical features of an oligodendroglioma and neurocytoma.

Leptomeningeal dissemination of an oligodendroglioma is rarely reported in the neurosurgical literature, especially in cases with a classical 1p19q deletion. The authors describe a case wherein a 1p19q deletion in a disseminated tumor with mixed immunohistochemical features of oligodendroglioma and neurocytoma was encountered and treated. Stereotactic right frontal craniotomy was undertaken for obtaining definitive histological diagnosis. The results revealed a neuroectodermal neoplasm with histologic and immunohistochemical features of oligodendroglioma and neurocytoma. FISH analysis confirmed classical 1p19q deletion. The patient was treated postoperatively with chemotherapy and radiation therapy. He showed good clinical response and remains alive 16 months after diagnosis.

Oligodendroglioma presenting with intradural spinal metastases: an unusual cause of cauda equina syndrome.

We report a 37-year-old man with a primary intracranial oligodendroglioma presenting later with symptomatic multiple cerebrospinal fluid (CSF) intradural drop spinal metastases. This patient initially presented in 2006 with complex partial seizures. Initial histology demonstrated World Health Organization (WHO) grade 2 oligodendroglioma. The patient had further generalised seizures 7 months after initial tumour resection. MRI at that time confirmed tumour recurrence. The patient underwent a repeat craniotomy. Histology showed anaplastic transformation to a WHO grade 3 oligodendroglioma. About 30 months after his initial presentation, the patient developed a focal neurological deficit in the left leg with associated retention of urine. MRI of the neuraxis demonstrated widespread leptomeningeal metastatic drop deposits within the spinal canal. We discuss the mechanisms involved in tumour dissemination throughout the CSF. We also review the relevant literature regarding this phenomenon.