Multiple approaches converge on three biological subtypes of meningioma and extract new insights from published studies.

One-fifth of meningiomas classified as benign by World Health Organization (WHO) histopathological grading will behave malignantly. To better diagnose these tumors, several groups turned to DNA methylation, whereas we combined RNA-sequencing (RNA-seq) and cytogenetics. Both approaches were more accurate than histopathology in identifying aggressive tumors, but whether they revealed similar tumor types was unclear. We therefore performed unbiased DNA methylation, RNA-seq, and cytogenetic profiling on 110 primary meningiomas WHO grade I and II). Each technique distinguished the same three groups (two benign and one malignant) as our previous molecular classification; integrating these methods into one classifier further improved accuracy. Computational modeling revealed strong correlations between transcription and cytogenetic changes, particularly loss of chromosome 1p, in malignant tumors. Applying our classifier to data from previous studies also resolved certain anomalies entailed by grouping tumors by WHO grade. Accurate classification will therefore elucidate meningioma biology as well as improve diagnosis and prognosis.

Suprasellar meningioma presenting with glaucomatous type cupping.

PURPOSE: To describe a case of a suprasellar meningioma compressing the chiasm from below and producing a unilateral fascicular (nasal) visual field defect that mimicked glaucomatous cupping. CASE REPORT: A 78-year-old man presented with painless, progressive, unilateral arcuate visual field defect. He was diagnosed with "normal tension glaucoma" based on an asymmetric cup to disc ratio. Despite treatment with anti-glaucoma drops, the visual field defect progressed. Neurophthalmic evaluation was consistent with a compressive optic neuropathy OD. Brain MRI showed a suprasellar meningioma compressing on the junction of the optic nerve and chiasm from below. CONCLUSION: Although junctional visual field loss (e.g. junctional scotoma and junctional scotoma of Traquair) are well-known presentations of compressive lesions at the optic chiasm, we describe a monocular, ipsilateral compressive superior nasal defect and asymmetric cupping as the presenting sign of a junctional compressive lesion mimicking glaucomatous cupping.

Malignant meningiomas.

Malignant meningiomas are WHO Grade III meningiomas representing 1% of all meningiomas. They are comprised of three histologic types: anaplastic, rhabdoid, and papillary. They can arise de novo or as a result of biologic progression of meningiomas of lower histologic grades. The overall survival of patients with WHO grade III meningiomas is 2-3 years. Surgery is the main treatment, while radiotherapy is thought to slow tumor growth. Multiple trials have been attempted on chemotherapeutic agents, hormonal therapies, small molecule and anti-angiogenic agents without robust evidence of efficacy. The rarity of these tumors is the main reason for our patchy understanding of the natural history and lack of effective treatment options. There is an urgent need to develop alternative therapies given the significantly increased risk of complication and co-mordibity associated with repeated surgeries in this population.

What's that big thing on your head? Diagnosis of a large frontoparietal lesion on an Eastern Zhou skull from Henan, China.

We carried out a differential diagnosis of a large frontoparietal lesion on a human skull from a Late Bronze Age archaeological site located on the Central Plain of China, dating to between 771 and 476 BC. The head of this individual was covered in cinnabar, a mercury-based pigment that later was used for medicinal purposes in China. The lesion was well-circumscribed and involved the outer and inner tables of the skull, slight diploë thickening, and coarsening of bone trabeculae with expansion of intertrabecular spaces. We show that the observed changes are most consistent with cavernous hemangioma of the skull, a benign vascular malformation that preferentially affects older adults. Hemangiomas are often neglected in the paleopathological literature because of their benign nature - they tend to be asymptomatic and do not affect quality of life to a significant degree. Nevertheless, they produce characteristic lesions that can be confused with several other conditions with unrelated etiologies, including congenital hemoglabinopathies, traumas, malignant or benign neoplasms, and Paget's disease. We outline the diagnostic criteria that distinguish cavernous hemangioma from other conditions affecting the skull.

Pathologic Laughter as an Early and Unusual Presenting Symptom of Petroclival Meningioma: a Case Report and Review of the Literature.

BACKGROUND: Pathologic laughter is inappropriate, involuntary, and unmotivated laughter episodes that may or may not be associated with mirth or amusement. Although associated with many diffuse brain pathologies, its association with intracranial focal mass lesions causing ventrolateral brainstem compression, like petroclival meningioma, is very rare. The exact pathophysiology of this interesting and unusual clinical symptom is unknown, but probably involves disinhibition and release of the so-called coordination center located in the upper brainstem due to compression by the tumor. CASE DESCRIPTION: A 26-year-old woman presented with recurrent episodes of inappropriate and involuntary laughter, which significantly affected her quality of life, for 2 years. These episodes did not resolve, and a magnetic resonance imaging of the brain showed a giant petroclival meningioma causing upper brainstem compression. Near-total excision of the tumor was done using an extended middle fossa approach. To our surprise, the pathologic laughter subsided immediately after surgery. CONCLUSIONS: Pathologic laughter may be the only symptom of a focal mass lesion causing ventrolateral upper brainstem compression, like petroclival meningioma, well before other neurological sign/symptoms appear. Tumors causing ventral brainstem compression must be ruled out before the patient is sent for a psychiatric evaluation.

An early investigative serum Raman spectroscopy study of meningioma.

Meningiomas represent one of the most frequently reported non-glial, primary brain and central nervous system (CNS) tumors. Meningiomas often display a spectrum of anomalous locations and morphological attributes, deterring their timely diagnosis. Majority of them are sporadic in nature and thus the present-day screening strategies, including radiological investigations, often result in misdiagnosis due to their aberrant and equivocal radiological facets. Therefore, it is pertinent to explore less invasive and patient-friendly biofluids such as serum for their screening and diagnostics. The utility of serum Raman spectroscopy in diagnosis and therapeutic monitoring of cancers has been reported in the literature. In the present study, for the first time, to the best of our knowledge, we have explored Raman spectroscopy to classify the sera of meningioma and control subjects. For this exploration, 35 samples each of meningioma and control subjects were accrued and the spectra revealed variance in the levels of DNA, proteins, lipids, amino acids and ß-carotene, i.e., a relatively higher protein, DNA and lipid content in meningioma. Subsequent Principal Component Analysis (PCA) and Principal Component-Linear Discriminant Analysis (PC-LDA) followed by Leave-One-Out Cross-Validation (LOOCV) and limited independent test data, in a patient-wise approach, yielded a classification efficiency of 92% and 80% for healthy and meningioma, respectively. Additionally, in the analogous analysis between healthy and different grades of meningioma, similar results were obtained. These results indicate the potential of Raman spectroscopy in differentiating meningioma. As present methods suffer from known limitations, with the prospective validation on a larger cohort, serum Raman spectroscopy could be an adjuvant/alternative approach in the clinical management of meningioma.

Systemic Rosai-Dorfman disease with central nervous system involvement.

Rosai-Dorfman disease (RDD) is a rare idiopathic and lymphoproliferative disorder. Central nervous system (CNS) involvement is infrequent and typically manifests as an isolated lesion. In this article, we describe an unusual case of RDD with multiple lesions in the CNS, upper respiratory tract and lymph nodes. A literature review revealed 45 cases (including the one described herein) of systemic RDD with CNS involvement documented to date. Among these cases, 29 (64.4%) presented with intracranial lesions, 10 (22.2%) with spinal lesions and 6 (13.3%) with both. While the condition of most patients was stable, only four died from RDD or for other reasons. Prognosis is good for most patients, even those with extensive lesions. Although there are various treatments for RDD, surgery is preferred. Given the rarity of RDD, multicenter international collaborations are advocated in order to study disease pathogenesis and develop effective treatment strategies.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND: Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN: A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION: ISRCTN71502099 on 19 May 2014.

Glaucomatous cupping and raised IOP: sine qua non for glaucoma?

PURPOSE: To present selected cases that highlight the confusions in daily glaucoma practice. METHODS: Four cases with raised or normal intraocular pressure (IOP) and definite glaucomatous cupping were investigated. RESULTS: While raised IOP was found in non-glaucomatous etiologies, IOP was normal in established glaucoma in a young patient. CONCLUSION: Raised IOP and glaucomatous cupping may not be pathognomonic of glaucoma and alternative etiology should be ruled out for appropriate management.

[Evaluation of manganese-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetate complex (Cyclomang) as paramagnetic contrast agent for magnetic resonance imaging].

Preclinical evaluation of a 0.5 M solution of the manganese(II)- trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetate complex (Mn-DCTA, Cyclomang) has been carried out with a view to substitution of potentially toxic gadolinium-containing paramagnetic contrast agents for clinical MRI routines. The toxicological tests of Mn(II)-DCTA were performed on mice and rats. Liquid phantoms were used for evaluating the relaxivity of Mn(II)-DCTA in comparison to that of Gd(III)-DTPA and Mn-DTPA. The diagnostic imaging properties of Mn(II)-DCTA were quantitatively assessed on dogs with cerebral meningeomas (n = 10). The LD50 upon single administration in rats was above 17 ml/kg, thus slightly exceeding the corresponding values for of Gd(III)-DTPA and Mn-DTPA. The relaxivity of Mn(II)-DCTA amounted to R1 = 3.68 (mM(-1) x s(-1)) and did not differ significantly from the values known for Gd-DTPA and Mn-DTPA. Mn(II)-DCTA ensured high-intensity contrast of tumor areas in brain of dogs. It is concluded that Mn(II)-DCTA can be employed as a paramagnetic contrast agent in routine MRI studies and is worth further clinical evaluation.

Incidental findings on brain Magnetic Resonance Imaging in long-term survivors of breast cancer treated with adjuvant chemotherapy.

PURPOSE: Incidental brain findings defined as previously undetected abnormalities of potential clinical relevance that are unexpectedly discovered at brain imaging and are unrelated to the purpose of the examination are common in the general population. Because it is unclear whether the prevalence of incidental findings in breast cancer patients treated with chemotherapy is different to that in the general population, we compared the prevalence in breast cancer survivors treated with chemotherapy to that in a population-based sample of women without a history of any cancer. PATIENTS AND METHODS: Structural brain MRI (1.5T) was performed in 191 female CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) chemotherapy-exposed breast cancer survivors. A reference group of 1590 women without a history of cancer was sampled from a population-based cohort study. All participants were aged 50 to 80 years. Five trained reviewers recorded the brain abnormalities. Two experienced neuro-radiologists reviewed the incidental findings. RESULTS: The cancer survivors had completed chemotherapy on average 21 years before. Of the 191 subjects, 2.6% had an aneurysm and 3.7% had a meningioma. The prevalence of meningiomas and aneurysms was not different between the groups. The prevalence of pituitary macro adenomas in the breast cancer survivors (1.6%) was higher than that in the reference group (0.1%) (OR=23.7; 95% CI 2.3-245.8). CONCLUSION: Contrary to commonly held opinions, we did not observe an increased prevalence of meningiomas in cancer survivors. Breast cancer survivors previously treated with chemotherapy are more likely to develop pituitary adenomas than persons without a history of cancer and chemotherapy treatment.

Meningioma pulmonar / Primary pulmonary meningioma

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[Optic nerve meningioma mimicking progression of glaucomatous axonal damage: a case report]. / Meningioma do nervo óptico simulando progressão de dano axonal glaucomatoso: relato de caso.

To report a case of an optic nerve sheath meningioma located at the optic canal area mimicking the progression of a glaucomatous axonal damage. A 60-year-old female patient developed progressive visual field loss and enlargement of the optic disc cup in the left eye while in treatment for primary open-angle glaucoma. Because of the rapid progression of axonal loss, the asymmetry of the visual field defect and the fact that intraocular pressure had been under control, a compressive optic neuropathy was suspected. A computerized tomography scan of the orbit was normal but a high-resolution magnetic resonance imaging demonstrated an optic nerve sheath meningioma located at the optic canal area. Compressive lesions of the anterior visual pathways are uncommon causes of optic disc cupping but should be considered in patients suspected of or undergoing treatment for glaucoma that present with atypical progression of visual loss.

Meningioma do nervo óptico simulando progressão de dano axonal glaucomatoso: relato de caso / Optic nerve meningioma mimicking progression of glaucomatous axonal damage: a case report

O objetivo é relatar um caso de meningioma da bainha do nervo óptico localizado na região do canal óptico simulando progressão de dano axonal glaucomatoso. Paciente de 60 anos em tratamento para glaucoma primário de ângulo aberto apresentou perda progressiva do campo visual e aumento da escavação do disco óptico à esquerda. Devido à rapidez e à assimetria da progressão do dano axonal, por causa da redução da acuidade visual e do aparente bom controle pressórico uma lesão compressiva do nervo óptico foi suspeitada. A tomografia computadorizada de órbitas foi normal, entretanto a imagem por ressonância magnética evidenciou um meningioma da bainha do nervo óptico na região do canal óptico. Afecções compressivas da via óptica anterior são causas incomuns de escavação do disco óptico, entretanto podem simular uma neuropatia glaucomatosa e devem ser lembradas nos pacientes com suspeita de glaucoma de baixa pressão intra-ocular ou em tratamento para glaucoma que apresentem evolução atípica da perda visual.

To report a case of an optic nerve sheath meningioma located at the optic canal area mimicking the progression of a glaucomatous axonal damage. A 60-year-old female patient developed progressive visual field loss and enlargement of the optic disc cup in the left eye while in treatment for primary open-angle glaucoma. Because of the rapid progression of axonal loss, the asymmetry of the visual field defect and the fact that intraocular pressure had been under control, a compressive optic neuropathy was suspected. A computerized tomography scan of the orbit was normal but a high-resolution magnetic resonance imaging demonstrated an optic nerve sheath meningioma located at the optic canal area. Compressive lesions of the anterior visual pathways are uncommon causes of optic disc cupping but should be considered in patients suspected of or undergoing treatment for glaucoma that present with atypical progression of visual loss.

Palinacousis - auditory perseveration: two cases and a review of the literature.

Palinacousis is an auditory illusion rarely reported in cases of temporal lobe dysfunction. Detailed observations where made by Jacobs et al. in 1973. Since that time, only a few other cases have been described in the literature. After reviewing the literature and comparing our clinical experience, we believe that palinacousis can occur as an aura, a simple partial seizure, a complex partial seizure, and/or a postictal event. Within one academic year, we observed two patients who experienced palinacousis. Palinacousis maybe more common than recognized in patients with receptive aphasias or diffuse cerebral dysfunction, whose language deficits preclude adequate description. It is important to differentiate palinacousis from auditory hallucinations seen in psychotic and psychiatric patients. Identification of palinacousis as an aura, simple partial seizure, complex partial seizure, and/or postictal phenomenon can help localize potential lesions and improve patient care.

Very late frontal relapse of medulloblastoma mimicking a meningioma in an adult: usefulness of 1H magnetic resonance spectroscopy and diffusion-perfusion magnetic resonance imaging for preoperative diagnosis: case report.

OBJECTIVE AND IMPORTANCE: We present a rare case of very long-term medulloblastoma relapse in an adult patient and discuss the pattern of recurrence and metabolic imaging of the tumor. CLINICAL PRESENTATION: A 45-year-old man was referred for evaluation of a frontobasal midline tumor 21 years after treatment of a cerebellar medulloblastoma by surgery followed by chemotherapy and craniospinal radiotherapy. Magnetic resonance images were suggestive of a meningioma. Several hypotheses were discussed, such as other radio-induced tumors, sarcomas, high-grade gliomas, or lymphomas (previous chemotherapy) and even recurrence of medulloblastoma. Preoperative exploration included H magnetic resonance single-voxel spectroscopy (35 and 135 ms echo time), diffusion imaging, and perfusion magnetic resonance imaging. INTERVENTION: On magnetic resonance spectroscopy, N-acetyl-aspartate and an elevated choline/creatine ratio were retrieved, with a huge unidentified peak at 1.27 parts per million (ppm). Myoinositol signal was present at both echo times. On diffusion imaging, the tumor appeared hyperintense, with a low apparent diffusion coefficient value of 0.689. In the perfusion study, the maximal relative cerebral blood volume was 2. Metabolic imaging favored the diagnosis of medulloblastoma over the initially suspected diagnosis of meningioma. The patient underwent complete removal of the tumor that was confirmed to be a metastasis of his primary medulloblastoma. The postoperative course was uneventful, and complementary courses of radiotherapy and chemotherapy were planned. CONCLUSION: Late relapse should be considered, even after several decades, on occurrence of a second intracranial tumor in this context. Our observation validates the clinical interest of preoperative metabolic imaging for brain tumors with distinctive pattern.

Boron neutron capture therapy for recurrent malignant meningioma. Case report.

Malignant meningioma is a rare brain tumor with a high risk of recurrence. If this tumor recurs after complete resection and adjuvant radiotherapy, there is no optimal treatment to control it. The authors report the first case of recurrent malignant meningioma treated using boron neutron capture therapy (BNCT). This 25-year-old pregnant woman presented with a large frontal tumor. After her baby was born, she underwent gross-total resection of the tumor. A second resection and three Gamma Knife surgeries could not control progression of the enhancing mass; therefore, the authors applied BNCT based on their experience with it in the treatment of malignant gliomas. The minimum tumor dose and maximum brain tissue dose were estimated as 39.7 Gy-Eq and less than 9.0 Gy-Eq, respectively. Before BNCT the patient was mobile by wheelchair only, whereas 1 week after therapy she was able to walk. Twenty-two weeks later she underwent a second BNCT for tumor regrowth on the contralateral side, and the lesion was subsequently reduced. The tumor volume was markedly decreased from 65.6 cm3 at the time of the first BNCT to 31.8 cm3 at 26 weeks thereafter. The treatment of recurrent malignant meningioma is difficult and has been discouraging thus far. Data in the present case indicate that BNCT may be a promising treatment option for this challenging tumor.

[Proton spectroscopy findings of meningioma].

OBJECTIVE: To evaluate the characteristics of 1HMRSI and its diagnostic value on meningioma. METHODS: The findings of conventional MRI and of 1HMRSI from 11 cases of clinically proven meningiomas and from 12 normal volunteers were comparatively analyzed. The imaging sequences included T1-weighted imaging and T2-weighted imaging; additionally T1-weighted imaging with injection of the contrast agent of Gd-DTPA was performed in all meningioma cases. Two-dimensional phase encoding of proton magnetic resonance spectroscopic imaging (2D 1HMRSI) were obtained in all cases. RESULTS: On conventional pre-contrast MRI, the signals in 8 meningioma cases showed medium or faintly low intensities and in 3 cases showed mixed intensities on T1WI. On T2WI, the signals in 7 cases showed medium or faintly high intensities and in 4 cases showed mixed intensities. After injection of Gd-DTPA, the solid portion of tumors exhibited obvious enhancement in all meningioma cases. "Dural trail sign" was revealed in 7 cases. Peri-tumor edema was evident in 11 meningioma cases. Compared with control group, 1HMRSI of all meningiomas revealed different spectral peaks, including absent acetylaspartate (NAA), prominent choline (Cho), and reduced phosphocreatine (Pcr). The ratios of Cho/Pcr obviously increased. The peak of lactate (Lac) was visualized in 2 meningioma cases. CONCLUSION: Most cases of meningioma can be diagnosed with conventional magnetic resonance imaging (MRI). 1HMRSI can yield more informative findings about meningioma via the observed metabolic materials changes in tumor cells. So conventional MRI is the most important technology for diagnosing meningioma and 1HMRS combined with MRI can improve the diagnostic accuracy. 1HMRSI can be an important supplemental means in the diagnosis of meningiomas.

Presumed optic nerve sheath meningioma diagnosed after complicated retrobulbar anesthesia.

We present a patient who developed acute visual loss and light flashes at retrobulbar anesthesia for cataract extraction. Vision improved only slightly after cataract surgery. Although traumatic optic neuropathy was suspected, the patient was diagnosed one year later with an optic nerve sheath meningioma (ONSM). ONSM is a rare, slow growing, benign tumour with highly variable clinical features. Diagnosis is often delayed. This case report demonstrates the diagnostic difficulty of this tumour.