Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge-Weber Syndrome.

BACKGROUND: Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM. METHODS: We enrolled 112 patients and classified them according to LCM distribution: (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS). RESULTS: The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups' EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups. CONCLUSION: Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.

Tamoxifen. A treatment for meningioma?

BACKGROUND: No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken. METHODS: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study. RESULTS: 251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47-67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4-3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6-24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, 95%CI[90.3-94.3] and 81.3%, 95%CI[75.2-88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, 95%CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, 95%CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment. CONCLUSION: Using this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose.

Improved Detection of Postoperative Residual Meningioma with [68Ga]Ga-DOTA-TOC PET Imaging Using a High-resolution Research Tomograph PET Scanner.

PURPOSE: PET with somatostatin receptor ligand [68Ga]Ga-DOTA-D-Phe1-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) is an established method in radiotherapy planning because of the improved detection and delineation of meningioma tissue. We investigated the diagnostic accuracy of supplementary [68Ga]Ga-DOTA-TOC PET in patients with a 3-month postoperative MRI reporting gross-total resection (GTR). EXPERIMENTAL DESIGN: Thirty-seven patients with a histologically proven meningioma and GTR on postoperative MRI were prospectively referred to [68Ga]Ga-DOTA-TOC PET. Detection and volume measurements of [68Ga]Ga-DOTA-TOC-avid lesions in relation to the primary tumor site were recorded. Residual tumor in suspicious lesions suggested by [68Ga]Ga-DOTA-TOC PET was verified by (i) tumor recurrence/progression on subsequent MRI scans according to the Response Assessment of Neuro-Oncology criteria, (ii) subsequent histology, and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scan. RESULTS: Twenty-three PET scans demonstrated [68Ga]Ga-DOTA-TOC-avid lesions suspicious of residual meningioma, where 18 could be verified by (i) tumor progression on subsequent MRI scans (n = 6), (ii) histologic confirmation (n = 3), and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scans confirming the initial PET findings (n = 9) after an overall median follow-up time of 17 months (range, 9-35 months). In contrast, disease recurrence was seen in only 2 of 14 patients without [68Ga]Ga-DOTA-TOC-avid lesions (P < 0.0001). The sensitivity, specificity, and diagnostic accuracy of [68Ga]Ga-DOTA-TOC PET in detecting meningioma residue was 90% [95% confidence interval (CI), 67-99], 92% (95% CI, 62-100), and 90% (95% CI, 74-98; P < 0.0001), respectively. CONCLUSIONS: The majority of patients with GTR on 3-month postoperative MRI may have small unrecognized meningioma residues that can be detected using [68Ga]Ga-DOTA-TOC PET.

Histological transformation in recurrent WHO grade I meningiomas.

Atypical or malignant transformation (AT/MT) has been described in WHO grade I meningiomas. Our aim was to identify predictive factors of AT/MT at recurrence. A total of N = 15 WHO grade increases were observed in N = 13 patients (0.96% of the study population, risk of transformation of 0.12% per patient-year follow-up). Patients with and without progression at recurrence were similar regarding age, gender distribution, skull-base location, bone infiltration, and Simpson grades. Recurrence-free survival was lower in patients with transformation (5 ± 4.06 years versus 7.3 ± 5.4 years; p = 0.03). Among patient age, gender, skull base location, extent of resection or post-operative RT, no predictor of AT/MT was identified, despite a follow-up of 10,524 patient-years. The annual risk of transformation of WHO grade I meningiomas was 0.12% per patient-year follow-up. Despite the important number of patients included and their extended follow-up, we did not identify any risk factor for transformation. A total of 1,352 patients with surgically managed WHO grade I meningioma from a mixed retro-and prospective database with mean follow-up of 9.2 years ± 5.7 years (0.3-20.9 years) were reviewed. Recurring tumors at the site of initial surgery were considered as recurrence.

Total DNA methylation as a biomarker of DNA damage and tumor malignancy in intracranial meningiomas.

BACKGROUND: Meningiomas are the most common primary intracranial tumors in adults. They are initially detected with neuroimaging techniques, but definite histological diagnosis requires tumor surgery to collect tumor tissue. Gross total resection is an optimal and final treatment for the majority of patients, followed by radiotherapy in malignant or refractory cases. However, there are a lot of uncertainties about i.a. the need for intervention in incidental cases, estimation of growth kinetics, risk of malignant transformation, or response to radiotherapy. Therefore a new diagnostic approach is needed. It has already been shown that epigenetics plays a crucial role in cancer biology, development, and progression. DNA methylation, the presence of 5-methylcytosine in DNA, is one of the main elements of a broad epigenetic program in a eukaryotic cell, with superior regulatory significance. Therefore, we decided to look at meningioma through changes of 5-methylcytosine. METHODS: We performed an analysis of the total amount of 5-methylcytosine in DNA isolated from intracranial meningioma tissues and peripheral blood samples of the same patients. The separation and identification of radioactively labeled nucleotides were performed using thin-layer chromatography. RESULTS: We found that the 5-methylcytosine level in DNA from intracranial meningiomas is inversely proportional to the malignancy grade. The higher the tumor WHO grade is, the lower the total DNA methylation. The amount of 5-methylcytosine in tumor tissue and peripheral blood is almost identical. CONCLUSIONS: We conclude that the total DNA methylation can be a useful marker for brain meningioma detection, differentiation, and monitoring. It correlates with tumor WHO grade, and the 5-methylcytosine level in peripheral blood reflects that in tumor tissue. Therefore it's applicable for liquid biopsy. Our study creates a scope for further research on epigenetic mechanisms in neurooncology and can lead to the development of new diagnostic methods in clinical practice.

Radiological and clinical findings of isolated meningeal Rosai-Dorfman disease of the central nervous system.

Rosai-Dorfman disease (RDD) with isolated central nervous system (CNS) involvement is an extremely rare disease. Most RDD of the CNS present as dural-based mass mimicking meningioma and other common lesions, which makes preoperative accurate diagnosis of great difficulty. We searched the pathology database in our hospital and 3 cases of RDD with isolated CNS involvement were finally included in our study. Radiological and clinical findings of these three cases were retrospectively analyzed. The lesions of 2 cases were dura-based against the cerebral convexity, presenting as a sheet-shaped thickened dura mater, another case was located just across the cerebral falx, the dural display in the center was intact. The 3 cases showed low signal intensity on T2-weighted image, obviously enhanced, significantly surrounding edema and finger-like protuberance but no invasion of the brain parenchyma or no sign of hyperplasia or sclerosis of the surrounding cranial bones. In conclusion, when we come across a disease that mimicking meningioma, especially when it manifests as the above radiological features, we should considered it might be a kind of proliferative disease of the meninges, such as RDD.

Unexpected diagnosis of spinal leptomeningeal metastatic disease on MRI myelography.

We present a case of leptomeningeal metastatic disease to the cauda equina detected on Magnetic Resonance myelography. The heavy T2-weighting and small field-of-view of this MRI technique are designed to detect CSF leaks, but also provide exquisite detail of the cauda equina and any associated nodularity. Magnetic Resonance myelography thus shows promise as an adjunct to the MRI evaluation of patients with suspected leptomeningeal metastatic disease and other tumours affecting the cauda equina.

Soft tissue grafts for dural reconstruction after meningioma surgery.

The meninges are involved in various pathologies and are often directly or indirectly severed during surgical procedures, especially the dura mater. This can pose a real challenge for the surgeon, as a proper reconstruction of the meninges is important to prevent complications such as cerebrospinal fluid leak (CSF). A variety of techniques for dural reconstruction have been described, employing natural and artificial materials. A novel technique for dural reconstruction involves soft tissue grafts in the form of fibrous or fibromuscular flaps, which are placed on the dural defects to seal the gaps. These soft tissue grafts represent an appropriate scaffold for cell ingrowth and fibrosis, thus preventing CSF. In this pilot study, we described the application of soft tissue grafts for dural reconstruction in 10 patients who underwent convexity meningioma surgery.

Surgical management of sacral meningeal cysts by obstructing the communicating holes with muscle graft.

BACKGROUND: The surgical indication and treatment of sacral meningeal cyst have not been well established and current methods are usually accompanied by complications and recurrence. The aim of this study is to discuss the treatment of symptomatic sacral meningeal cyst, by investigating the surgical results of our surgically treated patients, and minimize the complications and recurrence. METHODS: We retrospectively reviewed all patients with symptomatic sacral meningeal cysts who were surgically treated by a single surgeon in the same institution from 2002 to 2017. All patients underwent the same operation by incising the cyst wall and obstructing the communicating hole with muscle graft, while the cyst wall was left untreated instead of resected or imbricated. The obstruction was verified by doing a Valsalva-like maneuver. The preoperative symptoms and signs, and the outcomes at most recent follow-up were rated and compared by Neurological Scoring System. RESULTS: A total of 18 patients (7 male patients and 11 female patients, average age 42.3 years) were followed up for an average of 51.7 months. All patients had communicating holes linking the cysts and the dural sacs. The average preoperative neurological score was 19.7 ± 2.2, and it was improved to 23.2 ± 2.8 at the most recent follow-up (p < 0.01). CONCLUSIONS: The sacral meningeal cyst originated from the communication with the dural sac. Surgical treatment of symptomatic sacral meningeal cysts can yield a long-term resolution of the appropriately selected patient's symptoms. Obstructing the communicating hole with muscle graft is an effective and simple method to obliterate the cyst. The incised cyst wall can be left untreated instead of resected or imbricated.

Amelanotic Meningeal Melanoma with Leptomeningeal Dissemination: A Case Report and Systematic Literature Review.

BACKGROUND: Meningeal melanoma is a rare tumor of the central nervous system, whose amelanotic variant is called "amelanotic meningeal melanoma" (AMM). AMM does not produce melanin and therefore does not exhibit typical short T1 and short T2 signal on magnetic resonance imaging and thus can be easily misdiagnosed and be inappropriately managed. To date, only 4 AMM cases have been reported in the English literature. Here, we report the fifth case. CASE DESCRIPTION: A 26-year-old female patient presented with a 4-month history of progressive headache and nausea, the conventional magnetic resonance imaging demonstrated a posterior fossa mass accompanied by diffuse leptomeningeal dissemination. Repeated cerebrospinal fluid cytology screening showed negative results. The functional magnetic resonance examinations, including diffusion-weighted imaging, proton magnetic resonance spectroscopy, and dynamic susceptibility contrast perfusion-weighted imaging, provided complementary information. The final diagnosis of AMM was made by immunohistochemistry. Despite gross total excision of the tumor, the disease progressed, and the patient died 10 months after diagnosis. CONCLUSIONS: Our experience with this case demonstrated that meningeal melanoma should be included in the differential diagnosis when an intracranial mass is accompanied by leptomeningeal dissemination, and especially when proton magnetic resonance spectroscopy and dynamic susceptibility contrast perfusion-weighted imaging indicate a malignant tumor whereas diffusion-weighted imaging does not. And the loss of a typical melanin signal should not server as an excluding criterion for meningeal melanoma.

Huge multiple spinal extradural meningeal cysts in infancy.

BACKGROUND: Multiple spinal extradural meningeal cysts (SEMCs) are rare lesions. SEMCs communicate with the subarachnoid space through multiple dural defects and expand into the extradural space with progressive spinal cord compression. CASE PRESENTATION: We report a 5-month-old boy with hydronephrosis involving nine huge SEMCs that were distributed from the T1-L5 levels. Eight SEMCs, except for one small noncommunicating cyst, were exposed through laminoplastic laminotomy at the T10-L5 and T3-5 levels. Five transdural communications with dural defects were packed with a piece of autologous muscle and fibrin glue. Tenting sutures to lift up the dura to the vertebral arch were added to minimize the extradural dead space. Postoperatively, cord compression was relieved and hydronephrosis improved. CONCLUSION: In conclusion, packing of all dural defects and dural tenting sutures at a one-staged operation is useful in the surgical management of huge and multiple SEMCs in infancy.

Intracranial Meningeal Rosai-Dorfman Disease Mimicking Multiple Meningiomas: 3 Case Reports and a Literature Review.

BACKGROUND: Rosai-Dorfman disease (RDD) is a benign, self-limiting, and nonneoplastic histiocytic proliferative disorder with a poorly defined pathogenesis. Central nervous system involvement is extremely rare, particularly cases with multiple intracranial masses. There is no consensus on optimal treatment and management of RDD. CASE DESCRIPTION: In case 1, a 39-year-old man presented with headaches and paroxysmal convulsions of the limbs. Magnetic resonance imaging showed multiple solid masses located at the right frontoparietal and left frontal meningeal regions. The masses were surgically removed for staging, and the histologic diagnosis was consistent with RDD. In case 2, a 53-year-old man was admitted with epileptic seizures. Magnetic resonance imaging revealed multiple, homogeneously enhancing masses in the left parietal, temporal, and occipital meningeal regions. The largest mass was surgically removed, and histopathologic examination confirmed RDD. In case 3, a 9-year-old girl was admitted with bilateral exophthalmos and incomplete eyelid closure. Magnetic resonance imaging displayed multiple, heterogeneously enhancing masses in the right parietal meningeal region. All masses were surgically removed, and the histopathologic diagnosis was RDD. CONCLUSIONS: RDD with multiple isolated intracranial foci is rare but should be considered in the differential diagnosis when multiple meningiomas are suspected in children and adults. Preoperative diagnosis is challenging, and definitive diagnosis requires immunohistochemical examination. Surgical resection is the most effective therapy for rapid relief of symptoms.

Tumor-to-Lesion Metastasis: Case Report of Carcinoma Metastasis to Multiple Sclerosis Lesion.

BACKGROUND: The term "tumor-to-lesion metastasis" is an extension of "tumor-to-tumor metastasis," which is a rare but well-documented phenomenon. Tumor metastasis to the meninges and/or central nervous system (CNS) is rare in patents with multiple sclerosis (MS), although MS lesions bear many similarities to the primary tumor microenvironment and metastatic niche. We present the first case of malignant tumor metastasis to MS lesions with immunophenotyping of inflammatory cells in the metastatic foci. CASE DESCRIPTION: A 45-year-old male patient with a 6-year history of MS and newly diagnosed lung carcinoma developed carcinoma metastases in the meninges and CNS, as well as into mixed active/inactive MS lesions. The carcinoma-hosting MS lesions exhibited abundant macrophages/microglia with ongoing demyelination but rare T cells. In comparison, a 46-year-old female patient with a 21-month history of MS and newly diagnosed gastric carcinoma was found to have leptomeningeal carcinomatosis and separate active MS lesions containing not only frequent macrophages/microglia but also T cells. CONCLUSIONS: The carcinoma-hosting MS lesions are unlike typical active lesions but recapitulate the CNS metastatic niche. Our observations suggest that metastasis-hosting MS lesions might require a distinct immune microenvironment to be permissive to the seeding and growth of metastatic tumors.

Spinal Meninges and Their Role in Spinal Cord Injury: A Neuroanatomical Review.

Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. Compression of the spinal cord against the meninges in SCI patients causes a "compartment-like" syndrome. In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.

Meningioma with the unique coexistence of secretory and lipomatous components: A case report with immunohistochemical study.

Meningioma is the most common extra-axial neoplasm which accounts for 30% of all intracranial tumors with a female predilection. These tumors exhibit a broad spectrum of differentiation potency corresponding to different histological subtypes. Meningothelial cells can rarely show separate secretory or lipomatous (metaplastic) transformation. The coexistence of these two different histological subtypes in a single meningeal tumor is extremely rare with only two reported cases. We report an uncommon case of meningioma in a 40-year-old female showing histological admixture of both secretory and lipomatous (metaplastic) meningioma, which to our knowledge is only the third reported case in the world. It highlights the multipotency of phenotypic transformation of primary meningothelial cells. This rare tumor behaves in a fashion similar to benign meningioma of WHO Grade I type.

Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.

Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015. Focal LMD was targeted with SRS in 16 patients. The median imaging follow-up time was 7 months. The median volume of LMD was 372 mm3 and the median margin dose was 16 Gy. Five patients underwent prior WBRT. Histology included non-small cell lung (8), breast (5), melanoma (1), gastrointestinal (1) and ovarian cancer (1). Follow-up MR imaging was available for 14 patients. LMD was stable in 5 and partially regressed in 8 patients at follow-up. One patient had progression of LMD with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for focal LMD at a median time of 6 months. Overall, focal LMD may be may be treated successfully with radiosurgery, potentially delaying WBRT in some patients.

A Case of Leptomeningeal Dissemination of Pilocytic Astrocytoma in a Child.

We present the case of a 2-year-old boy with progressive left-sided weakness and a cranial magnetic resonance imaging (MRI) scan showing a lesion with a cystic component in the right thalamus and basal ganglia. The lesion was subtotally resected and diagnosed as a pilocytic astrocytoma by histopathology. Tumor seeding along the surgical tract was seen on MRI 16 days and 10 weeks after surgery. The patient received vincristine and carboplatin, and MRI performed 4 months after chemotherapy revealed no additional or residual lesions. This case illustrated that a World Health Organization grade I astrocytoma could disseminate along the surgical tract.

Derivation of Leptomeninges Explant Cultures from Postmortem Human Brain Donors.

Even though great progress has been made in the clinical characterization of Parkinson's disease, several studies report that the diagnosis of Parkinson's disease is not pathologically confirmed in up to 25% of clinically diagnosed Parkinson's disease. Therefore, tissue collected from clinically diagnosed patients with idiopathic Parkinson's disease can have a high rate of misdiagnosis; hence in vitro studies from such tissues to study Parkinson's disease as a preclinical model can become futile. By collecting postmortem human leptomeninges with a confirmed neuropathological diagnosis of Parkinson's disease and characterized by nigrostriatal cell loss and intracellular protein inclusions called Lewy bodies, one can be certain that clinically observed parkinsonism is not caused by another underlying disease process (e.g. tumor, arteriosclerosis). This protocol presents the dissection and preparation of postmortem human leptomeninges for derivation of a meningeal fibroblast culture. This procedure is robust and has a high success rate. The challenge of the culture is sterility as the brain procurement is generally not performed under sterile conditions. Therefore, it is important to supplement the culture media with a cocktail of penicillin, streptomycin, and amphotericin B. The derivation of meningeal fibroblasts from autopsy-confirmed cases with Parkinson's disease provides the foundation for in vitro modeling of Parkinson's disease. Meningeal fibroblasts appear 3-9 days after sample preparation and about 20-30 million cells can be cryopreserved in 6-8 weeks. The meningeal fibroblast culture is homogenous and the cells express fibronectin, a commonly used marker to identify meninges.