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Sample records for ponto cerebellar meningioma

  1. Speech prosody in Friedreich's and olivo-ponto cerebellar atrophy

    NASA Astrophysics Data System (ADS)

    Casper, Maureen

    2001-05-01

    A critical issue in the study of speech motor control is the identification of the mechanisms that generate the temporal flow of serially ordered articulatory events. Two staged models of serial ordered events (Lashley, 1951; Lindblom, 1963) claim that time controls events whereas dynamic models predict a relative relation between time and space. Each of these models predicts a different relation between the acoustic measures of formant frequency and segmental duration. The most recent method described herein provides a sensitive index of speech deterioration which is both acoustically robust and phonetically systematic. Both acoustic and magnetic resonance imaging measures were used to describe the speech disturbance in two neurologically distinct groups of cerebellar ataxia: Friedreich's ataxia and olivo-ponto cerebellar ataxia. The speaking task was designed to elicit six different prosodic conditions and four prosodic contrasts. All subjects read the same syllable embedded in a sentence, under six different prosodic conditions. Pair-wise comparisons derived from the six conditions were used to describe (1) final lengthening, (2) phrasal accent, (3) nuclear accent and (4) syllable reduction. An estimate of speech deterioration as determined by individual and normal subects' acoustic values of syllable duration, formant and fundamental frequencies was used in correlation analyses with magnetic resonance imaging ratings.

  2. Sporadically second localization of cerebellar hemangioblastoma in sella turcica mimicking a meningioma with no associated von Hippel-Lindau disease.

    PubMed

    Amelot, Aymeric; Bouazza, Schaharazad; Polivka, Marc; George, Bernard; Bresson, Damien

    2015-01-01

    A 72-year-old man presented with a gradual bilateral decrease in visual acuity. Imaging showed lesion in the sella turcica diagnosed as meningioma but proving secondarily to be a hemangioblastoma. His neurosurgical history included a resection of a cerebellar hemangioblastoma 30 years ago. To our knowledge, such a hemangioblastoma second localization from the infratentorial to supratentorial has not been reported in the literature for patients not presenting with von Hippel-Lindau disease. PMID:25817084

  3. Chronic In Vivo Imaging of Ponto-Cerebellar Mossy Fibers Reveals Morphological Stability during Whisker Sensory Manipulation in the Adult Rat123

    PubMed Central

    Rylkova, Daria; Crank, Aidan R.

    2015-01-01

    Abstract The cerebellum receives extensive disynaptic input from the neocortex via the basal pontine nuclei, the neurons of which send mossy fiber (MF) axons to the granule cell layer of the contralateral cerebellar hemisphere. Although this cortico-cerebellar circuit has been implicated in tasks such as sensory discrimination and motor learning, little is known about the potential role of MF morphological plasticity in the function of the cerebellar granule cell layer. To address this issue, we labeled MFs with EGFP via viral infection of the basal pons in adult rats and performed in vivo two-photon imaging of MFs in Crus I/II of the cerebellar hemisphere over a period of several weeks. Following the acquisition of baseline images, animals were housed in control, enriched, or deprived sensory environments. Morphological dynamics were assessed by tracing MF axons and their terminals, and by tracking the stability of filopodia arising from MF terminal rosettes. MF axons and terminals were found to be remarkably stable. Parameters derived neither from measurements of axonal arbor geometry nor from the morphology of individual rosettes and their filopodial extensions significantly changed under control conditions over 4 weeks of imaging. Increasing whisker stimulation by manipulating the sensory environment or decreasing such stimulation by whisker trimming also failed to alter MF structure. Our studies indicate that pontine MF axons projecting to Crus I/II in adult rats do not undergo significant structural rearrangements over the course of weeks, and that this stability is not altered by the sustained manipulation of whisker sensorimotor experience. PMID:26693178

  4. Functional unity of the ponto-cerebellum: evidence that intrapontine communication is mediated by a reciprocal loop with the cerebellar nuclei.

    PubMed

    Möck, Martin; Butovas, Sergejus; Schwarz, Cornelius

    2006-06-01

    The majority of cerebral signals destined for the cerebellum are handed over by the pontine nuclei (PN), which thoroughly reorganize the neocortical topography. The PN maps neocortical signals of wide-spread origins into adjacent compartments delineated by spatially precise distribution of cortical terminals and postsynaptic dendrites. We asked whether and how signals interact on the level of the PN. Intracellular fillings of rat PN cells in vitro did not reveal any intrinsic axonal branching neither within the range of the cells' dendrites nor farther away. Furthermore, double whole cell patch recordings did not show any signs of interaction between neighboring pontine cells. Using simultaneous unit recording in the PN and cerebellar nuclei (CN) in rats in vivo, we investigated whether PN compartments interact via extrinsic reciprocal connections with the CN. Repetitive electrical stimulation of the cerebral peduncle of < or = 40 Hz readily evoked rapid sequential activation of PN and CN, demonstrating a direct connection between the structures. Stimulation of the PN gray matter led to responses in neurons < or = 600 microm away from the stimulation site at latencies compatible with di- or polysynaptic pathways via the CN. Importantly, these interactions were spatially discontinuous around the stimulation electrode suggesting that reciprocal PN-CN loops in addition reflect the compartmentalized organization of the PN. These findings are in line with the idea that the cerebellum makes use of the compartmentalized map in the PN to orchestrate the composition of its own neocortical input. PMID:16641380

  5. [Multiple meningiomas].

    PubMed

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. PMID:27234913

  6. Checkpoint inhibition in meningiomas.

    PubMed

    Bi, Wenya Linda; Wu, Winona W; Santagata, Sandro; Reardon, David A; Dunn, Ian F

    2016-06-01

    Meningiomas are increasingly appreciated to share similar features with other intra-axial central nervous system neoplasms as well as systemic cancers. Immune checkpoint inhibition has emerged as a promising therapy in a number of cancers, with durable responses of years in a subset of patients. Several lines of evidence support a role for immune-based therapeutic strategies in the management of meningiomas, especially high-grade subtypes. Meningiomas frequently originate juxtaposed to venous sinuses, where an anatomic conduit for lymphatic drainage resides. Multiple populations of immune cells have been observed in meningiomas. PD-1/PD-L1 mediated immunosuppression has been implicated in high-grade meningiomas, with association between PD-L1 expression with negative prognostic outcome. These data point to the promise of future combinatorial therapeutic strategies in meningioma. PMID:27197540

  7. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO

    PubMed Central

    Clark, Victoria E.; Erson-Omay, E. Zeynep; Serin, Akdes; Yin, Jun; Cotney, Justin; Özduman, Koray; Avşar, Timuçin; Li, Jie; Murray, Phillip B.; Henegariu, Octavian; Yilmaz, Saliha; Günel, Jennifer Moliterno; Carrión-Grant, Geneive; Yılmaz, Baran; Grady, Conor; Tanrıkulu, Bahattin; Bakırcıoğlu, Mehmet; Kaymakçalan, Hande; Caglayan, Ahmet Okay; Sencar, Leman; Ceyhun, Emre; Atik, A. Fatih; Bayri, Yaşar; Bai, Hanwen; Kolb, Luis E.; Hebert, Ryan; Omay, S. Bulent; Mishra-Gorur, Ketu; Choi, Murim; Overton, John D.; Holland, Eric C.; Mane, Shrikant; State, Matthew W.; Bilgüvar, Kaya; Baehring, Joachim M.; Gutin, Philip H.; Piepmeier, Joseph M.; Vortmeyer, Alexander; Brennan, Cameron W.; Pamir, M. Necmettin; Kılıç, Türker; Lifton, Richard P.; Noonan, James P.; Yasuno, Katsuhito; Günel, Murat

    2016-01-01

    We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1E17K, a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive—nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics. PMID:23348505

  8. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.

    PubMed

    Clark, Victoria E; Erson-Omay, E Zeynep; Serin, Akdes; Yin, Jun; Cotney, Justin; Ozduman, Koray; Avşar, Timuçin; Li, Jie; Murray, Phillip B; Henegariu, Octavian; Yilmaz, Saliha; Günel, Jennifer Moliterno; Carrión-Grant, Geneive; Yilmaz, Baran; Grady, Conor; Tanrikulu, Bahattin; Bakircioğlu, Mehmet; Kaymakçalan, Hande; Caglayan, Ahmet Okay; Sencar, Leman; Ceyhun, Emre; Atik, A Fatih; Bayri, Yaşar; Bai, Hanwen; Kolb, Luis E; Hebert, Ryan M; Omay, S Bulent; Mishra-Gorur, Ketu; Choi, Murim; Overton, John D; Holland, Eric C; Mane, Shrikant; State, Matthew W; Bilgüvar, Kaya; Baehring, Joachim M; Gutin, Philip H; Piepmeier, Joseph M; Vortmeyer, Alexander; Brennan, Cameron W; Pamir, M Necmettin; Kiliç, Türker; Lifton, Richard P; Noonan, James P; Yasuno, Katsuhito; Günel, Murat

    2013-03-01

    We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics. PMID:23348505

  9. Vergence Deficits in Patients with Cerebellar Lesions

    ERIC Educational Resources Information Center

    Sander, T.; Sprenger, A.; Neumann, G.; Machner, B.; Gottschalk, S.; Rambold, H.; Helmchen, C.

    2009-01-01

    The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence…

  10. Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure

    PubMed Central

    Keser, Zafer; Hasan, Khader M.; Mwangi, Benson I.; Kamali, Arash; Ucisik-Keser, Fehime Eymen; Riascos, Roy F.; Yozbatiran, Nuray; Francisco, Gerard E.; Narayana, Ponnada A.

    2015-01-01

    Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC) pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI). Ten right-handed healthy subjects (7 males and 3 females, age range 20–51 years) were studied. DT-MRI data were acquired with a voxel size = 2 mm × 2 mm × 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC) and occipito-ponto-cerebellar (OPC). The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas) were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM), cerebral WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~25.8 ± 7.3 mL, or a percentage of 1.6 ± 0.45 of the total intracranial volume (ICV). PMID:25904851

  11. Cerebellar Hypoplasia

    MedlinePlus

    ... disorders that begin in early childhood, such as ataxia telangiectasia. In an infant or young child, symptoms of a disorder that features cerebellar hypoplasia might include floppy muscle tone, developmental or ...

  12. Cerebellar Degeneration

    MedlinePlus

    ... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

  13. Cerebellar liponeurocytoma.

    PubMed

    Owler, Brian K; Makeham, John M; Shingde, Meena; Besser, Michael

    2005-04-01

    A case of cerebellar liponeurocytoma in a 34-year-old man is reported. There are only 19 other cases reporting this entity in the medical literature. The diagnostic, radiological and clinical features associated with this tumour are reviewed and discussed in relation to our case. The differences in behaviour and prognosis between medulloblastoma and cerebellar liponeurocytoma are presented with the corresponding implications for management. PMID:15851097

  14. Acute cerebellar ataxia

    MedlinePlus

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  15. Surgical Treatment for Falcotentorial Meningiomas.

    PubMed

    Hong, Chang Ki; Hong, Je Beom; Park, Hunho; Moon, Ju Hyung; Chang, Jong Hee; Lee, Kyu Sung; Park, Seoung Woo

    2016-07-01

    Among intracranial meningiomas, falcotentorial meningiomas, occurring at the junction of the falx cerebri and tentorial dural folds, are extremely rare. Because of their deep location, they are surrounded by critical structures, and have been regarded as one of the most challenging lesions for surgical treatment. In this study, we describe our surgical strategy for falcotentorial meningiomas and provide a review of our experience. PMID:27189300

  16. Surgical Treatment for Falcotentorial Meningiomas

    PubMed Central

    Hong, Chang Ki; Hong, Je Beom; Park, Hunho; Moon, Ju Hyung; Chang, Jong Hee; Lee, Kyu Sung

    2016-01-01

    Among intracranial meningiomas, falcotentorial meningiomas, occurring at the junction of the falx cerebri and tentorial dural folds, are extremely rare. Because of their deep location, they are surrounded by critical structures, and have been regarded as one of the most challenging lesions for surgical treatment. In this study, we describe our surgical strategy for falcotentorial meningiomas and provide a review of our experience. PMID:27189300

  17. Epidural Cystic Spinal Meningioma

    PubMed Central

    Zhang, Ji; Chen, Zheng-he; Wang, Zi-feng; Sun, Peng; Jin, Jie-tian; Zhang, Xiang-heng; Zhao, Yi-ying; Wang, Jian; Mou, Yong-gao; Chen, Zhong-ping

    2016-01-01

    Abstract Cystic spinal meningioma (CSM) is an uncommon meningioma variant. Extradural CSMs are particularly rare and difficult to distinguish from other intraaxial tumors. This study presents a case of a 36-year-old woman with intraspinal extradual CSM at the thoracolumbar spine. She experienced persistent weakness, progressive numbness, and sensory disturbance in the right lower limb. Magnetic resonance imaging (MRI) of the patient revealed an irregular cystic mass at the thoracic 11 to lumbar 3 levels dorsally. This case was misdiagnosed as other neoplasms prior to surgery because of the atypical radiographic features and location of the tumor. Extradural CSMs should be considered in the differential diagnosis of intraspinal extradural cystic neoplasms. Complete removal of cystic wall provides an optimal outcome, rendering the lesion curable. PMID:26986119

  18. [Cerebellar stroke].

    PubMed

    Paradowski, Michał; Zimny, Anna; Paradowski, Bogusław

    2015-01-01

    Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke. PMID:26181157

  19. Natural history of multiple meningiomas

    PubMed Central

    Wong, Ricky H.; Wong, Andrew K.; Vick, Nicholas; Farhat, Hamad I.

    2013-01-01

    Background: Asymptomatic solitary meningiomas are typically managed with clinical and radiographic follow-up. Multiple meningiomas represents a clinical entity distinct from solitary meningiomas and can be sporadic, radiation-induced, associated with neurofibromatosis, or exhibit other familial inheritance. The growth rate for multiple meningiomas is not known and therefore management of these complicated patients can be difficult. Methods: A retrospective chart review was performed on 12 patients with a total of 55 meningiomas. Patients with neurofibromatosis were not included. Serial enhanced magnetic resonance imaging was used to determine tumor growth rates. Treatment history was also reviewed and included for analysis. Results: Analysis of all 55 tumors demonstrated an average rate of growth of 0.46 cm3/year (range: −0.57-2.94 cm3/year). In the 23 tumors that received no treatment, the average rate of growth was 0.34 cm3/year (range: −0.03-1.8 cm3/year). Ten of the 23 tumors that received no treatment had no history of cranial irradiation. This group demonstrated a growth rate of 0.44 cm3/year (range: −0.01-1.8 cm3/year). Linear regression analysis did not yield any significant relationship between tumor burden and rates of growth. Conclusion: Tumor growth rates in patients with multiple meningiomas did not appear to be higher than reported rates for incidentally found solitary meningiomas. As such, asymptomatic multiple meningioma patients should be managed with clinical and radiographic follow-up. PMID:23776757

  20. Cerebellar abiotrophy.

    PubMed

    DeBowes, R M; Leipold, H W; Turner-Beatty, M

    1987-08-01

    Cerebellar abiotrophy is a degenerative condition of Arabian horses that produces signs of head tremors and ataxia. Affected foals demonstrate clinical signs between the time of birth and 6 months of age. The condition is untreatable, although some animals have reportedly improved to varying degrees. The disease is believed to be inherited; however, definitive evidence is lacking at this time. PMID:3497695

  1. Rhabdoid Meningioma: Report of Two Cases

    PubMed Central

    Reddy, Ch. Karunakar; Rao, A. Divakar; Ballal, Chandra K.

    2015-01-01

    Rhabdoid meningioma is an uncommon anaplastic variant of meningioma. We describe the clinicoradiological and histomorphological features of two such cases of meningioma, with a brief review of literature. One case in a 9-year-old girl, presented initially as an atypical meningioma in the right fronto-parietal region, which on recurrence 18 months later, evolved into a rhabdoid meningioma. The second case in a 33-year-old male was located in the right parieto-occipital region. PMID:25859490

  2. Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

    ClinicalTrials.gov

    2016-02-26

    Acoustic Schwannoma; Adult Anaplastic Meningioma; Adult Ependymoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Meningeal Hemangiopericytoma; Adult Papillary Meningioma; Neurofibromatosis Type 1; Neurofibromatosis Type 2; Recurrent Adult Brain Tumor

  3. [Familial cerebellar ataxia: clinical, radiological and electrophysiological findings].

    PubMed

    Gajkowski, K; Rysz, A; Walecki, J; Bojakowski, J

    1988-01-01

    A family with cerebellar ataxia of late onset occurring in four generations was observed. Neurological abnormalities included signs of cerebellar ataxia, pyramidal tract damage and damage to the peripheral motor neuron. Computerized tomography demonstrated in five out of six studied patients an image suggesting olivo-ponto-cerebellar atrophy. In the cerebellar structures, brainstem and cerebral hemispheres evidence of atrophy was detected. No correlation was demonstrated between the intensity of the clinical signs and the progression of changes in CT image. Electrophysiological investigations demonstrated changes compatible with damage to the motor and sensory fibres in the peripheral nerves and signs suggesting damage to the spinal motor neurons and pyramidal tract. These observations confirm the multilevel development of the process. The use of similar diagnostic methods will permit a more accurate classification of cerebellar ataxia and obtaining of better information for prognostication of individual cases. PMID:3164096

  4. The Ponto bone-anchored hearing system.

    PubMed

    Westerkull, Patrik

    2011-01-01

    Based on a foundation of a well-documented Brånemark implant experience and the most advanced sound processing technology from Oticon, Oticon Medical introduced in 2009 a new bone-anchored hearing system, the Ponto system. Although the principle of percutaneous direct bone conduction is established, new technology aiming at improving speech perception and sound comfort in noisy environments is introduced with the new Ponto system. This has been possible by using the sound-processing platform from the most advanced conventional hearing aids from Oticon. Furthermore, specific steps have been taken aiming at improving the implant as well as the skin-penetrating abutment. The Ponto sound processor coupling has been developed to withstand long-term wear and tear. With the Ponto system, a new alternative is offered to the various groups of both new and existing users of bone-anchored hearing systems. In clinical studies of the Ponto Pro sound processor, the objective testing verified the high performance of the adaptive directionality system. The subjective questionnaires on speech perception and device handling also verified that the Ponto system offers efficient hearing rehabilitation as well as other user benefits. The Ponto system also includes possibilities to fit the sound processor 2 weeks after surgery. Referred clinical studies with the Ponto system have, however, not yet been published in the literature (autumn 2010).Clinical results have this far been presented at scientific conferences. PMID:21389702

  5. Involvement of epimutations in meningioma.

    PubMed

    Venza, Mario; Visalli, Maria; Beninati, Concetta; Catalano, Teresa; Biondo, Carmelo; Teti, Diana; Venza, Isabella

    2015-07-01

    Epimutations are heritable and reversible cell markers, which can influence cell function going beyond the effects of DNA mutations. They result from multiple and coordinated mechanisms able to modulate gene expression. Regarding the significance of epigenetics in meningioma, few and somehow contradictory results are available, although promising information has been obtained. Here we highlight the most recent advances about the impact of DNA methylation, histone modifications, and microRNA regulation on meningioma development as well as the interplay between genetic and epigenetic alterations. Data indicate that epigenetics can help to identify novel candidate genes for the management and treatment of meningioma. PMID:25930103

  6. Case Report: Pulmonary metastases of malignant meningioma

    PubMed Central

    Basunaid, Suhail; Franssen, Frits M.E.; Accord, Ryan; Hamid, Myrurgia Abdul; Mahesh, Shekar; Baumert, Brigitta G.; Schijns, Olaf E.M.G.

    2014-01-01

    Meningioma accounts for approximately one-third of primary central nervous system tumors. Most meningiomas are benign, although up to one third are classified as atypical or malignant. We describe a 63-year Caucasian male presenting with pleural metastases from an intracranial meningioma. Distant metastases from meningiomas are infrequently found in clinical practice and mostly are associated with atypical or malignant meningiomas. There is no standard treatment; however surgical resection of both the primary and metastatic lesions is the safest therapy. The overall prognosis of atypical meningiomas is poor. Our patient died one week after discharge from our hospital. PMID:25254095

  7. KINOMIC ALTERATIONS IN ATYPICAL MENINGIOMA

    PubMed Central

    Anderson, Joshua C.; Taylor, Robert B.; Fiveash, John B.; de Wijn, Rik; Gillespie, G. Yancey; Willey, Christopher D.

    2015-01-01

    Background We sought to profile Atypical Meningioma in a high-throughput manner to better understand the altered signaling within these tumors and specifically the kinases altered in recurrent atypical meningioma. Kinomic Profiles could be used to identify prognostic biomarkers for responders/non-responders to classify future patients that are unlikely to benefit from current therapies. Directly these results could be used to identify drug-actionable kinase targets as well. Methods Peptide-substrate microarray kinase activity analysis was conducted with a PamStation®12 analyzing the tyrosine kinome in each tumor kinetically against ~144 target peptides. These data were then analyzed relative to clinical outcome (e.g., tumor recurrence). Results 3 major clusters of atypical meningiomas were identified with highly variant peptides primarily being targets of EGFR family, ABL, BRK and BMX kinases. Kinomic analysis of recurrent atypical meningiomas indicated patterns of increased phosphorylation of BMX, TYRO3 and FAK substrates as compared to non-recurrent tumors. Conclusion The atypical meningiomas profiled here exhibited molecular sub-clustering that may have phenotypic corollaries predictive of outcome. Recurrent tumors had increases in kinase activity that may predict resistance to current therapies, and may guide selection of directed therapies. Taken together these data further the understanding of kinomic alteration in atypical meningioma, and the processes that may not only mediate recurrence, but additionally may identify kinase targets for intervention. PMID:27158663

  8. Medical treatment of recurrent meningiomas.

    PubMed

    Chamberlain, Marc C; Barnholtz-Sloan, Jill S

    2011-10-01

    Meningiomas are the second most common primary brain tumor and are primarily treated with surgery (with or without embolization) and radiotherapy. Increasingly today, meningiomas undergo multiple resections and two radiotherapy treatments (either stereotactic or conventional external beam) before consideration for hormonal, chemotherapy or targeted therapy. The failure of hormonal and cytotoxic chemotherapy in the treatment of recurrent meningioma and increasing understanding of potential molecular targets in meningioma has resulted in multiple studies utilizing single-agent targeted therapy directed at biologically relevant signaling pathways, such as somatostatin (Sandostatin(®) LAR, SOM230c), PDGF (imatinib), EGF (erlotinib) and VEGF (sunitinib and vatalanib). Early results using a targeted approach have been modest at best and are often associated with significant toxicity. Consequently and at present, the brain tumor guidelines recognize only three medical therapies for inoperable and radiation-refractory meningiomas: hydroxyurea, IFN-α and Sandostatin LAR, a somatostatin analogue. Clearly, there remains an unmet need in neuro-oncology with respect to the medical treatment of recurrent meningiomas. PMID:21955199

  9. Intraparenchymal Angiomatous Meningioma: A Diagnostic Dilemma

    PubMed Central

    Bansal, Divya; Gogoi, Priyanka; Nazir, Wazid; Tandon, Anupama

    2015-01-01

    Meningioma arises from the arachnoid cap cells of the cerebrum. Intraparenchymal meningiomas or meningiomas without dural attachment are rare. We report a case of 40-year-old male who presented with a history of headache, dizziness and gradual loss of vision since one year. Clinicoradiological diagnosis of a high grade glioma was considered. Tumour was excised and haematoxylin and eosin stained sections revealed a tumour comprised predominantly of variable sized blood vessels showing hyalinization in a background of plump spindle cells with oval vesicular nuclei. In view of these features angiomatous meningioma was suspected. However, to confirm the diagnosis, a panel of immunohistochemical markers including vimentin, EMA and GFAP was done and a final diagnosis of angiomatous meningioma was offered. Angiomatous meningioma is a rare variant of meningioma and even much rarer in the intraparenchymal location. Angiomatous meningioma should be considered in the differential diagnosis of highly vascular intraparenchymal brain tumours. PMID:26557529

  10. Meningioma after radiotherapy for malignancy.

    PubMed

    Morgenstern, Peter F; Shah, Kalee; Dunkel, Ira J; Reiner, Anne S; Khakoo, Yasmin; Rosenblum, Marc K; Gutin, Philip

    2016-08-01

    Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1years (range 0.04-33years). The mean radiation dose was 34Gy (range 16-60Gy) and latency time to meningioma was 26years (range 8-51years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy. PMID:27068012

  11. Incidental finding of meningioma on bone scintigraphy.

    PubMed

    Thakorlal, A; Wong, D C; Anderson, R J

    2005-06-01

    An incidental finding of an intracranial posterior fossa meningioma detected by bone scintigraphy is presented. Most of the published literature on the diagnosis of meningioma is on the use of CT and MRI. There is limited published literature on the detection of meningioma with bone scintigraphy. PMID:15932468

  12. Chordoid meningioma, part of a multiple intracranial meningioma: a case report & review.

    PubMed

    Sriram, Prabu Rau

    2013-07-01

    Chordoid meningioma, classified as atypical meningioma according to the World Health Organisation (WHO) classification, is a rare subtype, which represents only 0.5% of all meningiomas and is associated with a high incidence of recurrence. Multiple intracranial meningiomas are rare in non-neurofibromatosis patients. We present a female patient with both of these rare types of meningioma. The patient presented with two concurrent intracranial meningiomas, with one a meningotheliomatous subtype and the other a chordoid meningioma. Given the wide array of histological differential diagnoses in chordoid meningioma, immunohistochemistry has a significant role to play in differentiating them. Recurrence in chordoid meningioma can be generally predicted based on the extent of resection, the percentage of chordoid element, and proliferation indices. PMID:24044003

  13. Management of Atypical and Anaplastic Meningiomas.

    PubMed

    Buttrick, Simon; Shah, Ashish H; Komotar, Ricardo J; Ivan, Michael E

    2016-04-01

    Meningiomas are the most prevalent primary tumor of central nervous system origin and, although most neoplasms are benign, a small proportion exemplifies an aggressive profile characterized by high recurrence rates, pleomorphic histology, and overall resistance to standard treatment. Standard initial therapy for malignant meningiomas includes maximal safe surgical resection followed by focal radiation in certain cases. The role for chemotherapy during recurrence of these aggressive meningiomas is less clear. Prognosis is poor and recurrence of malignant meningiomas is high. This article provides an overview of atypical and anaplastic malignant meningiomas, their treatment, and ongoing research for more effective treatments. PMID:27012388

  14. Surgical Resectability of Skull Base Meningiomas.

    PubMed

    Goto, Takeo; Ohata, Kenji

    2016-07-15

    With recent advances in surgical technology such as preoperative imaging, neuro-monitoring, and surgical instruments, the surgical resectability of intracranial meningiomas has increased over the last two decades. This study reviewed clinical articles regarding the surgical treatment of meningiomas to clarify the role of surgical excision, with a focus on skull base meningiomas. We sub-classified clinical articles about skull base meningiomas into two categories (anterior and middle fossa meningiomas; and posterior fossa meningiomas) and reviewed papers in each category. In cases with anterior and middle fossa meningiomas, surgical resectability has reached a sufficient level to maximize functional preservation. In cases of posterior fossa meningioma, however, surgical respectability remains insufficient even with full use of recent surgical modalities. Continuous refining of operative procedures is required to obtain more satisfactory outcomes, especially for posterior fossa meningioma. In addition, recent long-term outcomes of stereotactic radiosurgery (SRS) were acceptable for controlling the skull base meningiomas. Therefore, combination with surgical excision and SRS should be considered in complicated skull base meningiomas. PMID:27076382

  15. Surgical Resectability of Skull Base Meningiomas

    PubMed Central

    GOTO, Takeo; OHATA, Kenji

    2016-01-01

    With recent advances in surgical technology such as preoperative imaging, neuro-monitoring, and surgical instruments, the surgical resectability of intracranial meningiomas has increased over the last two decades. This study reviewed clinical articles regarding the surgical treatment of meningiomas to clarify the role of surgical excision, with a focus on skull base meningiomas. We sub-classified clinical articles about skull base meningiomas into two categories (anterior and middle fossa meningiomas; and posterior fossa meningiomas) and reviewed papers in each category. In cases with anterior and middle fossa meningiomas, surgical resectability has reached a sufficient level to maximize functional preservation. In cases of posterior fossa meningioma, however, surgical respectability remains insufficient even with full use of recent surgical modalities. Continuous refining of operative procedures is required to obtain more satisfactory outcomes, especially for posterior fossa meningioma. In addition, recent long-term outcomes of stereotactic radiosurgery (SRS) were acceptable for controlling the skull base meningiomas. Therefore, combination with surgical excision and SRS should be considered in complicated skull base meningiomas. PMID:27076382

  16. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report.

    PubMed

    Ramanathan, Nithya; Kamaruddin, Khairul Azmi; Othman, Aizzat; Mustafa, Fadhli; Awang, Mohamed Saufi

    2016-05-01

    Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma. PMID:27418876

  17. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report

    PubMed Central

    Ramanathan, Nithya; Kamaruddin, Khairul Azmi; Othman, Aizzat; Mustafa, Fadhli; Awang, Mohamed Saufi

    2016-01-01

    Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma.

  18. Ultrastructural pathology of human peritumoural oedematous cerebellar cortex.

    PubMed

    Castejón, O J

    2016-01-01

    Cerebellar cortical biopsies of the peritumoural region of seven patients with cerebellar haemangioma, mesencephalic meningioma, cerebellopontine astrocytoma, cerebellopontine meningioma, and medulloblastoma of cerebellar vermis were examined by means of conventional transmission electron microscopy. Granule cells showed oedematous cytoplasm and mitochondria. Swollen Golgi cells exhibited lipofuscin granules and intranuclear inclusions. Both neuron cell types displayed swollen dendritic digits synapsing with afferent mossy fibre endings. Degenerated myelinated axons corresponding to afferent mossy and climbing fibres and efferent Purkinje cell axons were observed at the granular layer. Dense and clear ischaemic Purkinje cells established degenerated synapses with swollen parallel fibre synaptic varicosities. Degenerated Purkinje cell recurrent axonal collaterals were found at the molecular layer. Swollen and clear Bergmann glial cell cytoplasm was observed closely applied to the oedematous clear and dark Purkinje cell body, dendritic trunk, secondary and tertiary dendritic branches. Swollen climbing fibre endings featured by numerous microtubules and neurofilaments, and a decreased number of synaptic vesicles were observed making degenerated axo-spinodendritic synapses with clear and swollen dendritic spines from Purkinje, Golgi, basket and stellate cell dendrites. Swollen stellate neurons showed oedematous mitochondria. Lipofuscin-rich astrocytes and reactive phagocytic astrocytes were observed. The latter appeared engulfing haematogenous proteinaceous oedema fluid. All cerebellar neurons showed stress endoplasmic reticulum dysfunction featured by focal dilated cisterns and detachment of associated ribosomes. Myelin sheath degeneration was related with oligodendrocyte degenerating hydropic changes. The peritumoural ischaemic cerebellar nerve and glial cell abnormalities were related with neurobehavioral changes, tremor, nystagmus, dismetry and gait disturbance

  19. Radiation-induced meningiomas in pediatric patients

    SciTech Connect

    Moss, S.D.; Rockswold, G.L.; Chou, S.N.; Yock, D.; Berger, M.S.

    1988-04-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature.

  20. Primary extradural calvarial meningioma: case report.

    PubMed

    Damtie, Zenebe Gedlie

    2004-01-01

    Intracranial meningiomas usually develop intradurally with in the confines of the skull. Meningiomas originating in an extradural location are rare. A woman of 69 years had a hard mass located in the left parietal region. The neurological examination and laboratory data were with in normal limits. Plain skull X-rays revealed hyperostotic changes. The meningioma was removed in bloc. And histologically, it was found to be transitional type of menigioma. PMID:15884277

  1. Spinal meningiomas: surgical management and outcome.

    PubMed

    Gottfried, Oren N; Gluf, Wayne; Quinones-Hinojosa, Alfredo; Kan, Peter; Schmidt, Meic H

    2003-06-15

    Advances in imaging and surgical technique have improved the treatment of spinal meningiomas; these include magnetic resonance imaging, intraoperative ultrasonography, neuromonitoring, the operative microscope, and ultrasonic cavitation aspirators. This study is a retrospective review of all patients treated at a single institution and with a pathologically confirmed diagnosis of spinal meningioma. Additionally the authors analyze data obtained in 556 patients reported in six large series in the literature, evaluating surgical techniques, results, and functional outcomes. Overall, surgical treatment of spinal meningiomas is associated with favorable outcomes. Spinal meningiomas can be completely resected, are associated with postoperative functional improvement, and the rate of recurrence is low. PMID:15669787

  2. Incidental Meningiomas: Management in the Neuroimaging Era.

    PubMed

    Spasic, Marko; Pelargos, Panayiotis E; Barnette, Natalie; Bhatt, Nikhilesh S; Lee, Seung James; Ung, Nolan; Gopen, Quinton; Yang, Isaac

    2016-04-01

    The number of patient imaging studies has increased because of precautious physicians ordering scans when a vague symptom is presented; subsequently, the number of incidental meningiomas detected has increased as well. These brain tumors do not present with related symptoms and are usually small. MRI and computed tomographic scans most frequently capture incidental meningiomas. Incidental meningiomas are managed with observation, radiation, and surgical resection. Ultimately, a conservative approach is recommended, such as observing an incidental meningioma and then only radiating if the tumor displays growth, whereas a surgical approach is to be used only when proven necessary. PMID:27012387

  3. Atypical and ischemic features of embolized meningiomas.

    PubMed

    Matsuda, Ken; Takeuchi, Hiroaki; Arai, Yoshikazu; Kitai, Ryuhei; Hosoda, Tetsuya; Tsunetoshi, Kenzo; Arishima, Hidetaka; Sato, Kazufumi; Kikuta, Ken-Ichiro

    2012-01-01

    Preoperative embolization (POE) of meningiomas is widely used to facilitate surgical removal and to reduce intraoperative blood loss. The resulting necrosis and enhanced proliferation have been reported to affect subsequent histologic grading. However, there was little concern about ischemic features, for example small cells resembling atypical meningiomas, cytoplasmic vacuoles resembling clear cell meningioma, intercellular discohesion resembling rhabdoid meningioma, and perivascular cuffs resembling papillary meningioma. Therefore, the extent of these ischemic features was scored and Ki-67 staining indices were investigated in a POE group composed of 29 specimens of meningiomas treated with POE and compared with equivalent results for a non-POE group composed of 29 meningiomas that were not treated with POE. Small cells with high N/C ratios, cytoplasmic vacuoles, intercellular discohesion, and perivascular cuffs were significantly increased in the POE group (versus the non-POE group, p < 0.05). There were no significant differences of the Ki-67 index between the POE group (2.2%) and the non-POE group (1.9%) (p = 0.49). Our results suggest that small cell change resulting in necrosis may be followed by POE, and that clear cell-like, rhabdoid cell-like, or pseudopapillary pattern identified in meningiomas may also be induced by POE. Therefore, histological findings and determination of grading should be evaluated cautiously in cases of embolized meningiomas. PMID:21789536

  4. Germline and somatic mutations in meningiomas.

    PubMed

    Smith, Miriam J

    2015-04-01

    Meningiomas arise from the arachnoid layer of the meninges that surround the brain and spine. They account for over one third of all primary central nervous system tumors in adults and confer a significant risk of location-dependent morbidity due to compression or displacement. A significant increase in risk of meningiomas is associated with neurofibromatosis type 2 (NF2) disease through mutation of the NF2 gene. In addition, approximately 5% of individuals with schwannomatosis disease develop meningiomas, through mutation of the SWI/SNF chromatin remodeling complex subunit, SMARCB1. Recently, a second SWI/SNF complex subunit, SMARCE1, was identified as a cause of clear cell meningiomas, indicating a wider role for this complex in meningioma disease. The sonic hedgehog (SHH)-GLI1 signaling pathway gene, SUFU, has also been identified as the cause of hereditary multiple meningiomas in a large Finnish family. The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas. This review describes the known meningioma predisposition genes and their links to the recently identified somatic mutations. PMID:25857641

  5. Stereotactic radiosurgery for WHO grade I meningiomas.

    PubMed

    Sheehan, Jason P; Williams, Brian J; Yen, Chun Po

    2010-09-01

    Meningiomas represent a common intracranial tumor in the adult population. Although extirpation to achieve a gross total resection or at least decrease mass effect has been the mainstay of treatment, stereotactic radiosurgery has come to play an increasingly important role in the management of patients with meningiomas. Radiosurgery utilizes highly focused, beams of ionizing radiation to inactivate tumor cells. Image guidance and a steep dose fall off are critical features of this approach. The radiobiology of radiosurgery differs in certain advantageous ways from conventional radiotherapy. Radiosurgery initially was utilized to treat recurrent or residual skull base meningiomas. As success was observed in this setting, radiosurgery has gradually expanded its role so as to treat convexity meningiomas; it is also used as an upfront treatment for patients for whom clinical and neuro-imaging findings are consistent with a meningioma. Most large series demonstrate tumor control rates for patients with grade I meningiomas in excess of 85%. Neurological function is generally preserved or improved for patients with meningiomas. However, complications can occur. Longitudinal follow-up including neurologic and radiologic assessment is required. Single and multisession stereotactic radiosurgery will likely play an expanded role in the treatment of patients with meningiomas. PMID:20734218

  6. Metastatic Meningioma Presenting as Cancer of Unknown Primary

    PubMed Central

    Gupta, Vinay; Gonsalves, Wilson I.; Robinson, Steven I.

    2013-01-01

    We describe a case of anaplastic meningioma presenting in an extracranial osseous location, initially diagnosed as cancer of unknown primary. Although anaplastic meningioma comprise 3% of all meningiomas, this subtype is more likely to be associated with metastases. The increased degree of dedifferentiation in anaplastic meningioma makes diagnosis difficult, especially if characteristic imaging findings of meningioma are not identified. Adequate tissue for diagnostic purposes and appropriate imaging studies may help in establishing a definitive diagnosis. PMID:24416493

  7. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

    PubMed

    Bodranghien, Florian; Bastian, Amy; Casali, Carlo; Hallett, Mark; Louis, Elan D; Manto, Mario; Mariën, Peter; Nowak, Dennis A; Schmahmann, Jeremy D; Serrao, Mariano; Steiner, Katharina Marie; Strupp, Michael; Tilikete, Caroline; Timmann, Dagmar; van Dun, Kim

    2016-06-01

    region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops. PMID:26105056

  8. Meningioma Genomics: Diagnostic, Prognostic, and Therapeutic Applications

    PubMed Central

    Bi, Wenya Linda; Zhang, Michael; Wu, Winona W.; Mei, Yu; Dunn, Ian F.

    2016-01-01

    There has been a recent revolution in our understanding of the genetic factors that drive meningioma, punctuating an equilibrium that has existed since Cushing’s germinal studies nearly a century ago. A growing appreciation that meningiomas share similar biologic features with other malignancies has allowed extrapolation of management strategies and lessons from intra-axial central nervous system neoplasms and systemic cancers to meningiomas. These features include a natural proclivity for invasion, frequent intratumoral heterogeneity, and correlation between biologic profile and clinical behavior. Next-generation sequencing has characterized recurrent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA, which are collectively present in ~80% of sporadic meningiomas. Genomic features of meningioma further associate with tumor location, histologic subtype, and possibly clinical behavior. Such genomic decryption, along with advances in targeted pharmacotherapy, provides a maturing integrated view of meningiomas. We review recent advances in meningioma genomics and probe their potential applications in diagnostic, therapeutic, and prognostic frontiers. PMID:27458586

  9. Cerebellar and Brainstem Malformations.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. PMID:27423798

  10. Spontaneous Regression of an Incidental Spinal Meningioma

    PubMed Central

    Yilmaz, Ali; Kizilay, Zahir; Sair, Ahmet; Avcil, Mucahit; Ozkul, Ayca

    2016-01-01

    AIM: The regression of meningioma has been reported in literature before. In spite of the fact that the regression may be involved by hemorrhage, calcification or some drugs withdrawal, it is rarely observed spontaneously. CASE REPORT: We report a 17 year old man with a cervical meningioma which was incidentally detected. In his cervical MRI an extradural, cranio-caudal contrast enchanced lesion at C2-C3 levels of the cervical spinal cord was detected. Despite the slight compression towards the spinal cord, he had no symptoms and refused any kind of surgical approach. The meningioma was followed by control MRI and it spontaneously regressed within six months. There were no signs of hemorrhage or calcification. CONCLUSION: Although it is a rare condition, the clinicians should consider that meningiomas especially incidentally diagnosed may be regressed spontaneously. PMID:27275345

  11. Analysis of Gene Expression Profiling in Meningioma: Deregulated Signaling Pathways Associated with Meningioma and EGFL6 Overexpression in Benign Meningioma Tissue and Serum

    PubMed Central

    Wang, Xuanchun; Gong, Ye; Wang, Daijun; Xie, Qing; Zheng, Mingzhe; Zhou, Yu; Li, Qin; Yang, Zhen; Tang, Hailiang; Li, Yiming; Hu, Renming; Chen, Xiancheng; Mao, Ying

    2012-01-01

    Molecular mechanisms underlying the pathogenesis of meningioma are not fully elucidated. In this study, we established differential gene expression profiles between meningiomas and brain arachnoidal tissue by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis demonstrated that PI3K/Akt and TGFβ signaling pathways were up-regulated in fibroblastic meningioma, and focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. EGFL6 was one of the most up-regulated genes in fibroblastic meningioma by microarray analysis. Quantitative real-time PCR demonstrated that benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissue and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in other investigated tumors. ELISA analysis showed that patients with benign meningiomas and ovarian cancers had the highest serum levels of EGFL6 (mean concentration: 672 pg/ml for benign meningiomas, and 616 pg/ml for ovarian cancers). Healthy people and patients with other tumors, however, had low levels of serum EGFL6. In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively. We also presented evidence that EGFL6 was overexpressed in benign meningioma tissues and serum. PMID:23285163

  12. A retrospective analysis of meningioma in Central Texas.

    PubMed

    Fonkem, Ekokobe; Dandashi, Jad A; Stroberg, Edana; Garrett, David; Harris, Frank S; El Nihum, Ibrahim M; Cooper, James; Dayawansa, Samantha; Huang, Jason H

    2016-06-01

    Documented meningioma cases in Central Texas (USA) from 1976 to 2013 were studied utilizing the Scott & White Brain Tumor Registry. All the cases examined were histologically diagnosed as meningiomas. Of the 372 cases, most were benign tumors (p<0.05). A majority of the patients were females (p<0.05). Elderly individuals (>45years of age) superseded the younger patients in meningioma incidence (p<0.05). Previous data regarding meningioma epidemiology in Texas showed a higher incidence in black patients when compared to white patients. By contrast, this study's findings of Central Texas meningioma demographics show increased incidence of meningiomas in white patients (p<0.05). This interesting find in meningioma prevalence warrants further investigation with a larger sample size, in order to establish validity and further parse out possible causes of meningioma development among white individuals. PMID:26851351

  13. Meningiomas with Rhabdoid or Papillary Components : Prognosis and Comparison with Anaplastic Meningiomas

    PubMed Central

    Kim, Jeong-Kwon; Jung, Shin; Lee, Kyung-Hwa; Kim, Seul-Kee; Lee, Eun Jung

    2016-01-01

    Papillary and rhabdoid meningiomas are pathologically World Health Organization (WHO) grade III. Any correlation between clinical prognosis and pathologic component is not clear. We analyzed the prognoses of patients with meningiomas with a rhabdoid or papillary component compared to those of patients with anaplastic meningiomas. From 1994 to June 2013, 14 anaplastic meningiomas, 6 meningiomas with a rhabdoid component, and 5 meningiomas with papillary component were pathologically diagnosed. We analyzed magnetic resonance imaging (MRI) findings, extent of removal, adjuvant treatment, progression-free survival (PFS), overall survival (OS), and pathologic features of 14 anaplastic meningiomas (group A), 5 meningiomas with a predominant (≥50%) papillary or rhabdoid component (group B1), and 6 meningiomas without a predominant (<50%) rhabdoid or papillary component (group B2). Homogeneous enhancement on MRI was associated with improved PFS compared to heterogeneous enhancement (p=0.025). Depending on pathology, the mean PFS was 134.9±31.6 months for group A, 46.6±13.4 months for group B1, and 118.7±19.2 months for group B2. The mean OS was 138.5±24.6 months for group A and 59.7±16.8 months for group B1. All recurrent tumors were of the previously diagnosed pathology, except for one tumor from group B1, which recurred as an atypical meningioma without a papillary component. Group B1 tumors showed a more aggressive behavior than group B2 tumors. In group B2 cases, the pathologic findings of non-rhabdoid/papillary portion could be considered for further adjuvant treatment. PMID:27446516

  14. Meningiomas with Rhabdoid or Papillary Components : Prognosis and Comparison with Anaplastic Meningiomas.

    PubMed

    Kim, Jeong-Kwon; Jung, Tae-Young; Jung, Shin; Lee, Kyung-Hwa; Kim, Seul-Kee; Lee, Eun Jung

    2016-07-01

    Papillary and rhabdoid meningiomas are pathologically World Health Organization (WHO) grade III. Any correlation between clinical prognosis and pathologic component is not clear. We analyzed the prognoses of patients with meningiomas with a rhabdoid or papillary component compared to those of patients with anaplastic meningiomas. From 1994 to June 2013, 14 anaplastic meningiomas, 6 meningiomas with a rhabdoid component, and 5 meningiomas with papillary component were pathologically diagnosed. We analyzed magnetic resonance imaging (MRI) findings, extent of removal, adjuvant treatment, progression-free survival (PFS), overall survival (OS), and pathologic features of 14 anaplastic meningiomas (group A), 5 meningiomas with a predominant (≥50%) papillary or rhabdoid component (group B1), and 6 meningiomas without a predominant (<50%) rhabdoid or papillary component (group B2). Homogeneous enhancement on MRI was associated with improved PFS compared to heterogeneous enhancement (p=0.025). Depending on pathology, the mean PFS was 134.9±31.6 months for group A, 46.6±13.4 months for group B1, and 118.7±19.2 months for group B2. The mean OS was 138.5±24.6 months for group A and 59.7±16.8 months for group B1. All recurrent tumors were of the previously diagnosed pathology, except for one tumor from group B1, which recurred as an atypical meningioma without a papillary component. Group B1 tumors showed a more aggressive behavior than group B2 tumors. In group B2 cases, the pathologic findings of non-rhabdoid/papillary portion could be considered for further adjuvant treatment. PMID:27446516

  15. Angiomatous meningioma in Sturge-Weber syndrome.

    PubMed

    Ahmed, Zubair; Prayson, Richard A

    2015-06-01

    We report a case of an intraventricular angiomatous meningioma arising in a 3-year-old boy diagnosed with Sturge-Weber syndrome (SWS) who presented with intractable epilepsy and right-sided hemiparesis. He underwent surgical resection of the epileptogenic focus. Histologic sections showed the typical findings of SWS accompanied by adjacent mild focal cortical dysplasia (International League Against Epilepsy Type Ib pattern; Palmini et al. Type IA). A small intraventricular mass, which was incidentally noted on imaging studies, was also excised. The mass showed a prominent venous vasculature with intermixed meningothelial cells, consistent with an angiomatous meningioma World Health Organization Grade I. SWS is a rare, sporadically occurring disorder marked by a port wine stain (hemangioma of the skin) arising in the distribution of the trigeminal nerve accompanied by an angiomatous proliferation in the leptomeninges. The underlying cortex often shows prominent dystrophic mineralization and gliosis. Patients often present with seizures and may require surgical resection when seizures prove to be pharmacoresistant. Meningiomas in SWS are a rare occurrence (only one known previously reported case) and angiomatous meningioma in SWS has never been described. The literature is briefly reviewed and the pathogenesis of hemangiomas in SWS and its implication in angiomatous meningioma is discussed. PMID:25766367

  16. Suprasellar Clear Cell Meningioma in an Infant

    PubMed Central

    Anunobi, Charles C.; Bankole, Olufemi; Ikeri, Nzechukwu Z.; Adeleke, Nurudeen A.

    2016-01-01

    Clear cell meningiomas are an uncommon subtype of meningioma rarely seen in infancy. We report a case of clear cell meningioma in an 8-month-old male infant. He presented at the Lagos University Teaching Hospital, Lagos, Nigeria, in 2015 with persistent vomiting, poor feeding and failure to thrive over a four month period. Generalised hypertonia and hyperreflexia were noted on examination. Computed tomography of the brain revealed a huge largely isodense suprasellar mass with a hypodense core. The tumour, which measured 6 × 5 × 4 cm, enhanced non-uniformly with contrast injection and extended to occlude the third ventricle. The patient underwent a bifrontal craniotomy with subtotal tumour excision. Six hours postoperatively, he went into cardiac arrest and could not be resuscitated. A histological diagnosis of clear cell meningioma was made as the tumour cells were immunoreactive to epithelial membrane antigen, S100 protein and vimentin. This case of clear cell meningioma was unusual due to its early occurrence and supratentorial location. PMID:27606120

  17. Genetic and molecular alterations in meningiomas.

    PubMed

    Alexiou, George A; Markoula, Sofia; Gogou, Pinelopi; Kyritsis, Athanasios P

    2011-05-01

    Meningiomas are the most common benign intracranial tumors in adults arising from the dura matter. The etiology of meningiomas is mostly unknown, although several risk factors have been described, such as ionizing radiation, head injury, hormones and genetic factors. According to WHO they are classified into 3 grades, grade I, grade II and grade III. Meningiomas express various hormonal and growth factor receptors, such as progesterone, estrogen, somatostatin, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors, which may be related to their biological behavior and response to treatment. Chromosomal abnormalities linked to meningiomas involve chromosomes 22, 1p, 9p, 10p, 11, 14q, 15, 17, and 18q. In addition, genes that may be involved in the formation of meningiomas include NF2, DAL-1, p14 (ARF), p53, MDM2, Rb, p16 and c-myc. It is likely that detailed molecular information will aid in establishing a molecular grading of these tumors and predict response to treatment and survival. PMID:21227570

  18. Suprasellar Clear Cell Meningioma in an Infant.

    PubMed

    Anunobi, Charles C; Bankole, Olufemi; Ikeri, Nzechukwu Z; Adeleke, Nurudeen A

    2016-08-01

    Clear cell meningiomas are an uncommon subtype of meningioma rarely seen in infancy. We report a case of clear cell meningioma in an 8-month-old male infant. He presented at the Lagos University Teaching Hospital, Lagos, Nigeria, in 2015 with persistent vomiting, poor feeding and failure to thrive over a four month period. Generalised hypertonia and hyperreflexia were noted on examination. Computed tomography of the brain revealed a huge largely isodense suprasellar mass with a hypodense core. The tumour, which measured 6 × 5 × 4 cm, enhanced non-uniformly with contrast injection and extended to occlude the third ventricle. The patient underwent a bifrontal craniotomy with subtotal tumour excision. Six hours postoperatively, he went into cardiac arrest and could not be resuscitated. A histological diagnosis of clear cell meningioma was made as the tumour cells were immunoreactive to epithelial membrane antigen, S100 protein and vimentin. This case of clear cell meningioma was unusual due to its early occurrence and supratentorial location. PMID:27606120

  19. Transformation of a meningioma with atypical imaging

    PubMed Central

    Kumar, Ashish; Deopujari, Chandrashekhar; Karmarkar, Vikram

    2016-01-01

    Meningiomas are benign tumors of the central nervous system. They have long term curability if they are excised completely. If not, they can recur after a prolonged period and can lead to increased morbidity during re-surgery. Recurrence is rarely associated with invasiveness. Usually de-differentiation in case of meningiomas is uncommon without any predisposing factors including different genetic mutations or radiation to the involved region. We report a case of a 38-year-old female who was operated for a benign para-sagittal meningioma 8 years back and subsequently developed an invasive recurrence off late. Also this time, the imaging morphology was slightly different for a meningioma and gross as well as microscopic findings were very atypical. Awareness for such cases must be there while dealing with recurrent meningiomas as invasiveness may not always be associated with adverse predisposing factors like radiation. As invasiveness is always a histopathological diagnosis, picking up such features on imaging is a daunting task and if done, can help neurosurgeons prognosticate such invasive recurrences in a better fashion. PMID:27366271

  20. Transformation of a meningioma with atypical imaging.

    PubMed

    Kumar, Ashish; Deopujari, Chandrashekhar; Karmarkar, Vikram

    2016-01-01

    Meningiomas are benign tumors of the central nervous system. They have long term curability if they are excised completely. If not, they can recur after a prolonged period and can lead to increased morbidity during re-surgery. Recurrence is rarely associated with invasiveness. Usually de-differentiation in case of meningiomas is uncommon without any predisposing factors including different genetic mutations or radiation to the involved region. We report a case of a 38-year-old female who was operated for a benign para-sagittal meningioma 8 years back and subsequently developed an invasive recurrence off late. Also this time, the imaging morphology was slightly different for a meningioma and gross as well as microscopic findings were very atypical. Awareness for such cases must be there while dealing with recurrent meningiomas as invasiveness may not always be associated with adverse predisposing factors like radiation. As invasiveness is always a histopathological diagnosis, picking up such features on imaging is a daunting task and if done, can help neurosurgeons prognosticate such invasive recurrences in a better fashion. PMID:27366271

  1. Radiation therapy for primary optic nerve meningiomas

    SciTech Connect

    Smith, J.L.; Vuksanovic, M.M.; Yates, B.M.; Bienfang, D.C.

    1981-06-01

    Optic nerve sheath meningiomas, formerly thought to be rare, have been encountered with surprising frequency since the widespread use of computed tomography. Early diagnosis led to an enthusiastic surgical approach to these lesions, but this has been tempered by the realization that even in the best of hands, blindness followed such surgery with distressing frequency. Optic nerve sheath meningiomas may be divided into primary, secondary, and multiple meningioma groups. Five patients with primary optic nerve sheath meningiomas treated with irradiation therapy are presented in this report. Improvement in visual acuity, stabilization to increase in the visual field, and decrease in size to total regression of optociliary veins, have been documented following irradiation therapy of the posterior orbital and intracanalicular portions of the optic nerve in some of these cases. Although each patient must be carefully individualized, there is no question that visual palliation can be achieved in some cases of optic nerve sheath meningioma. Further investigation of this therapeutic modality in selected cases in advised.

  2. Unilateral cerebellar aplasia.

    PubMed

    Boltshauser, E; Steinlin, M; Martin, E; Deonna, T

    1996-02-01

    We describe three children with unilateral cerebellar aplasia (UCA). Deliveries at term and neonatal periods were uneventful. Pregnancy was normal in one and complicated by mild bleeding (in second and fourth month respectively) in two instances. Presenting signs were delayed motor development with marked contralateral torticollis (n = 1), hemiplegia (n = 1) and unusual head nodding (n = 1). Neuroradiological investigations revealed complete aplasia (n = 1) and subtotal aplasia (n = 2) of one cerebellar hemisphere with only a residual wing-like structure below the tentorium. There was contralateral underdevelopment of the brainstem. The infant with hemiplegic cerebral palsy had an additional supratentorial periventricular parenchymal defect, contralateral to the cerebellar hypoplasia. In view of literature reports, describing similar neuroradiological or neuropathological findings in asymptomatic individuals, it is doubtful whether UCA is responsible for our patient's problems. In our cases UCA has presumably resulted from a prenatal destructive lesion, possibly an infarct, but the timing and exact nature are unknown. PMID:8677027

  3. Periostin: a novel prognostic predictor for meningiomas.

    PubMed

    Liu, Yi; Shi, Jin; Chen, Ming; Cao, Yong-fu; Liu, Ya-wei; Pan, Jun; Qi, Song-tao

    2015-02-01

    The expression and role of periostin in meningiomas remains unknown. Tissue specimens of 175 convexity meningiomas were immunohistochemically examined with antibodies against periostin and Ki67. The expression levels of periostin and Ki67 were compared among different WHO groups. The role of periostin and Ki67 in postoperative prognosis of meningiomas was also analyzed. Negative (-) expression of Ki67 was observed in 101 (57.7 %) cases of all the surgical tissue samples. The Ki67 expressions differed significantly among the WHO groups (P < 0.001) and correlated positively with the WHO grade (r = 0.673, P < 0.001). Low/negative staining of periostin was observed in 116 (66.3 %) cases. The periostin expressions differed significantly among the WHO groups (P < 0.001). Periostin expression correlated positively with the WHO grade (r = 0.742, P < 0.001). There was a positive correlation between Ki67 expression and periostin (r = 0.513, P < 0.001). Both Ki67 expression and periostin expression was found statistically different between brain invasion tumor and non-invasion tumor (p < 0.001). The recurrence rate and PFS rate in both varied Ki67 expression groups and periostin expression groups was statistically different (P < 0.001). The survival time and PFS time in both varied Ki67 expression groups and periostin expression groups was also statistically different (P < 0.001). Periostin was expressed in tumor stroma of meningiomas. Both periostin and Ki67 may behave as a maker in predicting the grade and prognosis in meningiomas. Drugs that targets periostin aims at reducing invasion of meningioma patients should be further researched. PMID:25519301

  4. Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

    ClinicalTrials.gov

    2014-07-09

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Mixed Glioma; Recurrent Adult Brain Tumor

  5. Pediatric meningiomas an aggressive subset: A clinicopathological and immunohistochemical study

    PubMed Central

    Hui, M; Uppin, MS; Saradhi, M Vijaya; Sahu, BP; Purohit, AK; Sundaram, C

    2015-01-01

    Background: Meningiomas are uncommon neoplasms in the pediatric age group and differ in various aspects from their adult counterparts. They account for 0.4-4.6% of all primary brain tumors. Aims: To retrospectively analyze the clinicopathological and immunohistochemical features of pediatric meningiomas. Materials and Methods: Meningiomas in patients under 18 years of age diagnosed between January 2001 to December 2011 were analyzed retrospectively. The hematoxylin and eosin stained sections and Ki 67 labelling index (LI) were reviewed for all the cases Results: The pediatric meningiomas accounted for 1.52% of total meningiomas (15/983). The mean age at presentation was 12 years with male to female ratio of 1.5:1. The presenting symptoms were headache, seizures, and motor deficits. The histology included 9 cases (60%) of atypical meningioma (WHO grade II) followed by 4 cases (26.67%) of WHO grade-I and 2 cases (13.33%) of anaplastic meningioma (WHO grade III). Five cases had a recurrence. Ki67 LI ranged from 0.5% to 1.5% in grade I, 0.5% to 15% in grade II and 13% to 24% in grade III meningiomas. Conclusion: Meningiomas are rare in children and show a male preponderance. There was a higher incidence of atypical and anaplastic meningiomas in pediatric population. PMID:25511215

  6. SU11657 Enhances Radiosensitivity of Human Meningioma Cells

    SciTech Connect

    Milker-Zabel, Stefanie Bois, Angelika Zabel-du; Ranai, Gholamreza; Trinh, Thuy; Unterberg, Andreas; Debus, Juergen; Lipson, Kenneth E.; Abdollahi, Amir; Huber, Peter E.

    2008-03-15

    Purpose: To analyze the effect of the multireceptor tyrosine kinase inhibitor SU11657 (primarily vascular endothelial growth factor, platelet-derived growth factor) in combination with irradiation in freshly isolated primary human meningioma cells. Methods and Materials: Tumor specimens were obtained from meningioma patients undergoing surgery at the Department of Neurosurgery, University of Heidelberg, Germany. For the present study only cells up to passage 6 were used. Benign and atypical meningioma cells and human umbilical vein endothelial cells (HUVEC) were treated with SU11657 alone and in combination with 6-MV photons (0-10 Gy). Clonogenic survival and cell proliferation were determined alone and in coculture assays to determine direct and paracrine effects. Results: Radiation and SU11657 alone reduced cell proliferation in atypical and benign meningioma cells as well as in HUVEC in a dose-dependent manner. SU11657 alone also reduced clonogenic survival of benign and atypical meningioma cells. SU11657 increased radiosensitivity of human meningioma cells in clonogenic survival and cell number/proliferation assays. The anticlonogenic and antiproliferative effects alone and the radiosensitization effects of SU11657 were more pronounced in atypical meningioma cells compared with benign meningioma cells. Conclusion: Small-molecule tyrosine kinase inhibitors like SU11657 are capable of amplifying the growth inhibitory effects of irradiation in meningioma cells. These data provide a rationale for further clinical evaluation of this combination concept, especially in atypical and malignant meningioma patients.

  7. Meningioma of Foramen Magnum Causing Drop Attacks

    PubMed Central

    Mahore, Amit; Mavani, Sandip; Rangarajan, Vithal; Patil, Manoj; Sathe, Prashant; Kawale, Juhi; Tikeykar, Vishakha

    2015-01-01

    A 52-year-old female presented with frequent episodes of falls without loss of consciousness. These episodes lasted for brief period followed by full neurological recovery. Magnetic resonance imaging (MRI) of the brain showed foramen magnum meningioma encasing left vertebral artery. The patient had dramatic improvement after excision of the tumor. PMID:25793133

  8. Dilemmas and diagnostic difficulties in meningioma.

    PubMed

    Hallinan, J T P D; Hegde, A N; Lim, W E H

    2013-08-01

    This article will review the uncommon locations and morphological features of meningiomas, which are important to recognize in order to avoid misdiagnosis. Uncommon locations will be demonstrated at the cerebellopontine angle, pineal, optic, intraventricular, and intradiploic regions. Unusual imaging features including cysts, metaplastic changes, and peritumoural oedema will also be discussed. PMID:23623578

  9. Intraventricular trigonal meningioma: Neuronavigation? No, thanks!

    PubMed Central

    Silva, Danilo O. A.; Matis, Georgios K.; Costa, Leonardo F.; Kitamura, Matheus A. P.; Birbilis, Theodossios A.; Azevedo Filho, Hildo R. C.

    2011-01-01

    Background: Most of the time meningiomas are benign brain tumors and surgical removal ensures cure in the vast majority of the cases. Thus, whenever possible, complete surgical resection should be the goal of the treatment. Methods: This is a report of our surgical technique for the operative resection of a trigonal meningioma in a resource-limited setting. The necessity of accurate and deep knowledge of the regional anatomy is outlined. Results: A 44-year-old male presented to our outpatient clinic complaining of cephalalgia increasing in frequency and intensity over the last month. His neurological exam was normal, yet a brain computed tomography scan revealed a lesion in the right trigone of the ventricular system. The diagnosis of possible meningioma was set. After thoroughly informing the patient, tumor resection was decided. An intraparietal sulcus approach was favored without the use of any modern technological aids such as intraoperative magnetic resonance imaging or neuronavigation. The postoperative course was uneventful and a postoperative computed tomography scan demonstrated the complete resection of the tumor. The patient was discharged two days later with no neurological deficits. In a two-year-follow-up he remains recurrence-free. Conclusion: In the current cost-effective era it is still possible to safely remove an intraventricular trigonal meningioma without the convenience of neuronavigation. Since the best neuronavigator is the profound neuroanatomical knowledge, no technological advancement could replace a well-educated and trained neurosurgeon. PMID:21886886

  10. Primary extracranial meningioma of the mandible.

    PubMed

    Mosqueda-Taylor, Adalberto; Domínguez-Malagon, Hugo; Cano-Valdez, Ana-Maria; Montiel-Hernandez, Ana-Maria

    2009-04-01

    Meningiomas are benign tumors of mesodermal origin that arise from arachnoid cell clusters that penetrate the dura to form arachnoid villi. These neoplasms represent one of the most common neoplasms developing within the central nervous system and are usually located at points of entry of vessels and nerves through the dura. Extracranial meningiomas (EM) comprise only 2% of all meningiomas, and only six cases of primary EM of the jawbones have been described to date. They may arise as an extension of intracranial meningiomas or as primary tumors and may be clinically indistinguishable from other benign tumours of the jaws, as they usually present as a well-delineated unencapsulated tumors. In this article a case of primary intramandibular primary EM that appeared as a well-defined osteolytic radiolucent lesion of the jaw is reported. The salient clinico-pathological features of this case is compared to those previously reported in the literature and differential diagnosis and therapeutic considerations are discussed. PMID:19333184

  11. Meningioma of foramen magnum causing drop attacks.

    PubMed

    Mahore, Amit; Ramdasi, Raghvendra; Mavani, Sandip; Rangarajan, Vithal; Patil, Manoj; Sathe, Prashant; Kawale, Juhi; Tikeykar, Vishakha

    2015-01-01

    A 52-year-old female presented with frequent episodes of falls without loss of consciousness. These episodes lasted for brief period followed by full neurological recovery. Magnetic resonance imaging (MRI) of the brain showed foramen magnum meningioma encasing left vertebral artery. The patient had dramatic improvement after excision of the tumor. PMID:25793133

  12. Spinal metastases from pituitary hemangiopericytic meningioma

    SciTech Connect

    Kumar, P.P.; Good, R.R.; Skultety, F.M.; Masih, A.S.; McComb, R.D.

    1987-10-01

    A rare, previously irradiated, recurrent malignant angioblastic meningioma of the pituitary, hemangiopericytic type, was locally controlled by a new endocurietherapy technique that allows delivery of very high (10,000 cGy), sharply localized irradiation. Rather than succumbing to the local tumor recurrence, as would otherwise be expected, the patient developed distant spinal metastases several years later.

  13. Mifepristone (RU 486) treatment of meningiomas.

    PubMed Central

    Lamberts, S W; Tanghe, H L; Avezaat, C J; Braakman, R; Wijngaarde, R; Koper, J W; de Jong, H

    1992-01-01

    Meningiomas are common brain tumours which are generally benign, well circumscribed and slow growing. In a minority of patients complete surgical removal is not possible and re-growth of tumour tissue is a major clinical problem. Most meningiomas contain progesterone receptors. The anti-progestational drug mifepristone (RU 486) binds to these receptors. Ten patients were treated with 12 recurrent or primary "inoperable" meningiomas, all of whom had shown recent neuroradiological and/or ophthalmological evidence of tumour growth. They received 200 mg mifepristone daily for 12 months. Most patients initially had complaints of nausea, vomiting and/or tiredness. In four patients prednisone (7.5 mg/day) was given after which these side-effects subsided. CT scan analysis of tumour size, showed progression of growth of five meningiomas in four patients, stable disease in three patients with three tumours and regression of four tumours in three patients. A decrease in the complaints of headache and an improved general well being was observed in five patients. Two patients died during the treatment period from unrelated causes. Mifepristone treatment resulted in control of tumour growth (= stable disease) in six of 10 patients who had shown recent evidence of tumour growth. In three of these six patients consistent tumour shrinkage was observed. PMID:1619417

  14. Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias.

    PubMed

    Mitoma, Hiroshi; Adhikari, Keya; Aeschlimann, Daniel; Chattopadhyay, Partha; Hadjivassiliou, Marios; Hampe, Christiane S; Honnorat, Jérôme; Joubert, Bastien; Kakei, Shinji; Lee, Jongho; Manto, Mario; Matsunaga, Akiko; Mizusawa, Hidehiro; Nanri, Kazunori; Shanmugarajah, Priya; Yoneda, Makoto; Yuki, Nobuhiro

    2016-04-01

    In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias. PMID:25823827

  15. Recurrent meningioma of the scalp after 13 years.

    PubMed

    Ashmore, Daniel Lee; Clancy, Rachel; Chumas, Paul D

    2016-01-01

    Meningiomas represent some of the most common types of tumour of the central nervous system. They are considered benign, with ∼1 in 1000 known to metastasise. We report a case of recurrent meningioma of the scalp 13 years following craniotomy to treat the primary. The recurrent tumour of the scalp was eventually excised 5 years later and the defect closed with an anterolateral thigh free flap in a joint procedure between the neurosurgeons and plastic surgeons. Histology of the scalp lesion confirmed a WHO grade I meningioma. Although a number of explanations for recurrent scalp meningiomas exist, the precise role of isolated genetic defects in scalp meningiomas is incomplete. The scalp meningioma in this case consisted of a complex karyotype suggestive of more aggressive disease. This case emphasises that cytogenetics may play a greater role in identifying more aggressive tumours than histology alone. PMID:27389725

  16. Multiple Meningiomas in a Patient with Cowden Syndrome

    PubMed Central

    Pain, Margaret; Darbinyan, Armine; Fowkes, Mary; Shrivastava, Raj

    2016-01-01

    Background  Cowden syndrome is a rare, multisystem disease manifesting with increased hamartomas and neoplasms. Though meningioma has been documented in patients with Cowden syndrome, the relationship between these two phenomena is still unclear. Case Description  We report a case of a 43-year-old female patient with a known PTEN mutation and clinical history of Cowden syndrome. A workup of headache demonstrated two skull base meningiomas. At the time of surgery, several additional tiny meningiomas were detected in the same region. Conclusions  The development of multiple meningiomas in a patient with predisposition for tumor is more than coincidental. Though PTEN mutations and deletions have not been shown to be critical for meningioma development, this case challenges that conclusion. In light of recent genetic advances in meningioma molecular pathogenesis, the role of the PTEN/AKT/PI3K pathway is discussed. PMID:27563534

  17. Metronidazole induced cerebellar ataxia

    PubMed Central

    Hari, Aditya; Srikanth, B. Akshaya; Lakshmi, G. Sriranga

    2013-01-01

    Metronidazole is a widely used antimicrobial usually prescribed by many specialist doctors for a short duration of 10-15 days. Prolonged use of metronidazole is rare. The present case is of a patient who used the drug for 4 months and developed peripheral neuropathy, convulsions, and cerebellar ataxia. He was treated with diazepam and levetiracetam. The patient recovered completely following discontinuation of metronidazole. PMID:23833378

  18. [Meningioma of the apex of the tentorial incisura. Diagnostic and surgical aspects apropos of a series of 7 cases].

    PubMed

    Guyotat, J; Bret, P; Rémond, J; Fischer, G

    1991-01-01

    Seven cases of meningiomas implanted on the medial portion of the free edge of the tentorium are reported. The denomination "meningiomas of the apex of the tentorial incisura" is proposed. In 4 patients, the clinical presentation was that of an intracranial hypertension without signs of compression of the quadrigeminal plate involvement. In the other 3 patients, the initial symptoms were those of the triad of the adult chronic hydrocephalus (N.P.H.) syndrome. Angiographic evaluation provides useful informations on the arterial supply (which is mainly from the tentorial branches of the internal carotid arteries and occasionally from the middle meningeal arteries) and the relationships of the tumor with the deep venous system. C.T. and M.R.I. facilitate earlier diagnosis and better demonstration of implantation and extension of the tumor, which the selection of a surgical approach is based upon. Four patients have undergone an occipital supratentorial approach and 2 a supra-cerebellar infra-tentorial approach. The meningioma was totally removed in 5 patients, sub-totally in 1 to avoid bilateral lesions of the visual pathways and cortical areas. The 7th patient was treated by C.S.F. shunt alone. No operative mortality occurred. The follow-up is averaging 18 months: 4 patients are symptom-free, 3 exhibit minor sequelae (epilepsy: 1, visual field defects: 2, memory impairement: 2). Six patients of the series have resumed their previous activities. Discussion is focused on the difficulties of surgical removal of this particular type of tentorial meningioma, resulting from volume, implantation and relationships of the tumor with the deep veins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2017287

  19. Pathology and Molecular Genetics of Meningioma: Recent Advances

    PubMed Central

    SHIBUYA, Makoto

    2015-01-01

    Meningiomas are the most common intracranial primary neoplasm in adults. Although the spectrum of clinical and molecular genetic issues regarding meningiomas remains undefined, novel genetic alterations that are associated with tumor morphology, malignancy, or location have recently been discovered. This review focuses on recent advances in understanding of the heterogenous pathology of meningiomas, particularly on associations between the clinical, histological, etiological, epidemiological, and molecular genetical aspects of the neoplasm. PMID:25744347

  20. Cavernous Hemangioma of the Skull and Meningioma: Association or Coincidence?

    PubMed Central

    Kilani, M.; Darmoul, M.; Hammedi, F.; Ben Nsir, A.; Hattab, M. N.

    2015-01-01

    Intraosseous cavernous hemangiomas of the skull are rare. Meningiomas are quite frequently encountered in a neurosurgical practice. The association between these two entities is nevertheless very uncommon. The authors present a case of a 72-year-old woman suffering from headache. The MRI showed a parietal meningioma with adjacent thick bone. The meningioma and the bone were removed. The histological examination confirmed the diagnosis of meningioma and revealed a cavernoma of the skull. The relationship between the lesions suggests more than a coincidental association. Several hypotheses are proposed to explain common causal connections. PMID:25960899

  1. Loss of SUFU Function in Familial Multiple Meningioma

    PubMed Central

    Aavikko, Mervi; Li, Song-Ping; Saarinen, Silva; Alhopuro, Pia; Kaasinen, Eevi; Morgunova, Ekaterina; Li, Yilong; Vesanen, Kari; Smith, Miriam J.; Evans, D. Gareth R.; Pöyhönen, Minna; Kiuru, Anne; Auvinen, Anssi; Aaltonen, Lauri A.; Taipale, Jussi; Vahteristo, Pia

    2012-01-01

    Meningiomas are the most common primary tumors of the CNS and account for up to 30% of all CNS tumors. An increased risk of meningiomas has been associated with certain tumor-susceptibility syndromes, especially neurofibromatosis type II, but no gene defects predisposing to isolated familial meningiomas have thus far been identified. Here, we report on a family of five meningioma-affected siblings, four of whom have multiple tumors. No NF2 mutations were identified in the germline or tumors. We combined genome-wide linkage analysis and exome sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU, a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family. The variation was not present in healthy controls, and all seven meningiomas analyzed displayed loss of the wild-type allele according to the classic two-hit model for tumor-suppressor genes. In silico modeling predicted the variant to affect the tertiary structure of the protein, and functional analyses showed that the activity of the altered SUFU was significantly reduced and therefore led to dysregulated hedgehog (Hh) signaling. SUFU is a known tumor-suppressor gene previously associated with childhood medulloblastoma predisposition. Our genetic and functional analyses indicate that germline mutations in SUFU also predispose to meningiomas, particularly to multiple meningiomas. It is possible that other genic mutations resulting in aberrant activation of the Hh pathway might underlie meningioma predisposition in families with an unknown etiology. PMID:22958902

  2. Review of controversies in management of non-benign meningioma.

    PubMed

    Paldor, Iddo; Awad, Mohammed; Sufaro, Yuval Z; Kaye, Andrew H; Shoshan, Yigal

    2016-09-01

    Meningiomas are one of the most common brain tumors. World Health Organisation (WHO) Grade II and Grade III meningiomas are grouped together as non-benign meningioma (NBM). There are several controversies surrounding NBM management, including the significance of extent of resection and the efficacy of post-operative radiation and drug treatment. We reviewed the literature to develop recommendations for management of NBM. The questions we sought to answer were: Does gross total resection (GTR) improve patient outcome? Is radiation therapy (RT) warranted after complete or after incomplete resection of NBM? What drug therapies have been proven to improve outcome in patients with NBM? We found that GTR improves outcome in WHO Grade II meningioma, and should be attempted whenever considered safe. GTR correlates less closely to outcome in Grade III meningioma compared to subtotal resection (STR). Extreme measures to completely resect Grade III meningioma are not warranted. RT following GTR of Grade II meningioma does not improve patient outcome, and may be reserved for recurrence. RT improves outcome following STR of Grade II meningioma. RT improves outcome after resection of Grade III meningioma. No drug therapy has been shown to improve outcome in NBM. This review elucidates recommendations for some of the controversies involving NBM. PMID:27338209

  3. Meningioma and occlusive vasculopathy: coexisting complications of past extracranial radiation

    SciTech Connect

    Montanera, W.; Chui, M.; Hudson, A.

    1985-07-01

    Two cases are reported in which a meningioma and occlusion of the internal carotid artery with development of transdural collateral circulation coexisted following extracranial radiation in childhood.

  4. Stereotactic radiotherapy of meningiomas compressing optical pathways

    SciTech Connect

    Hamm, Klaus-Detlef . E-mail: khamm@erfurt.helios-kliniken.de; Henzel, Martin; Gross, Markus W.; Surber, Gunnar; Kleinert, Gabriele; Engenhart-Cabillic, Rita

    2006-11-15

    Purpose: Microsurgical resection is usually the treatment of choice for meningiomas, especially for those that compress the optical pathways. However, in many cases of skull-base meningiomas a high risk of neurological deficits and recurrences exist in cases where the complete tumor removal was not possible. In such cases (fractionated) stereotactic radiotherapy (SRT) can offer an alternative treatment option. We evaluated the local control rate, symptomatology, and toxicity. Patients and Methods: Between 1997 and 2003, 183 patients with skull-base meningiomas were treated with SRT, among them were 65 patients with meningiomas that compressed optical pathways (64 benign, 1 atypical). Of these 65 cases, 20 were treated with SRT only, 27 were subtotally resected before SRT, and 18 underwent multiple tumor resections before SRT. We investigated the results until 2005, with a median follow-up of 45 months (range, 22-83 months). The tumor volume (TV = gross tumor volume) ranged from 0.61 to 90.20 cc (mean, 18.9 cc). Because of the risk of new visual disturbances, the dose per fraction was either 2 or 1.8 Gy for all patients, to a total dose of 50 to 60 Gy. Results: The overall survival and the progression-free survival rates for 5 years were assessed to 100% in this patient group. To date, no progression for these meningiomas have been observed. Quantitatively, tumor shrinkage of more than 20%, or more than 2 mm in diameter, was proved in 35 of the 65 cases after SRT. In 29 of the 65 patients, at least 1 of the symptoms improved. On application of the Common Toxicity Criteria (CTC), acute toxicity (Grade 3) was seen in 1 case (worsening of conjunctivitis). Another 2 patients developed late toxicity by LENT-SOMA score, 1 x Grade 1 and 1 x Grade 3 (field of vision loss). Conclusion: As a low-risk and effective treatment option for tumor control, SRT with 1.8 to 2.0 Gy per fraction can also be recommended in case of meningiomas that compress optical pathways. An

  5. [Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

    PubMed

    Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

    2015-01-01

    Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components. PMID:24954915

  6. Olfactory groove meningiomas: approaches and complications.

    PubMed

    Aguiar, Paulo Henrique Pires de; Tahara, Adriana; Almeida, Antonio Nogueira; Simm, Renata; Silva, Arnaldo Neves da; Maldaun, Marcos Vinicius Calfatt; Panagopoulos, Alexandros Theodoros; Zicarelli, Carlos Alexandre; Silva, Pedro Gabriel

    2009-09-01

    Olfactory groove meningiomas (OGM) account for 4.5% of all intracranial meningiomas. We report 21 patients with OGMs. Tumors were operated on using three surgical approaches: bifrontal (7 patients), fronto-pterional (11 patients) and fronto-orbital (3 patients). Total tumor removal (Simpson Grade 1) was achieved in 13 patients and Simpson II in 8 patients. Perioperative mortality was 4.76%. The average size of the OGM was 4.3+/-1.1cm. The overall recurrence rate was 19%. We preferred to use the pterional approach, which provides quick access to the tumor with less brain exposure. It also allows complete drainage of cisternal cerebrospinal fluid, providing a good level of brain relaxation during surgery. However, for long, thin tumors, hemostasis can be difficult using this approach. PMID:19577476

  7. Epidural Cystic Spinal Meningioma: A Case Report.

    PubMed

    Zhang, Ji; Chen, Zheng-He; Wang, Zi-Feng; Sun, Peng; Jin, Jie-Tian; Zhang, Xiang-Heng; Zhao, Yi-Ying; Wang, Jian; Mou, Yong-Gao; Chen, Zhong-Ping

    2016-03-01

    Cystic spinal meningioma (CSM) is an uncommon meningioma variant. Extradural CSMs are particularly rare and difficult to distinguish from other intraaxial tumors. This study presents a case of a 36-year-old woman with intraspinal extradual CSM at the thoracolumbar spine. She experienced persistent weakness, progressive numbness, and sensory disturbance in the right lower limb. Magnetic resonance imaging (MRI) of the patient revealed an irregular cystic mass at the thoracic 11 to lumbar 3 levels dorsally. This case was misdiagnosed as other neoplasms prior to surgery because of the atypical radiographic features and location of the tumor.Extradural CSMs should be considered in the differential diagnosis of intraspinal extradural cystic neoplasms. Complete removal of cystic wall provides an optimal outcome, rendering the lesion curable. PMID:26986119

  8. Microsurgical resection of giant intraventricular meningioma.

    PubMed

    Liu, James K

    2013-01-01

    Intraventricular meningiomas are rare tumors, accounting for approximately 0.5 to 3% of all intracranial meningiomas. The majority arise in the atrium of the lateral ventricle. The surgical management of these tumors remains a considerable challenge because of their deep location and proximity to critical structures. Complete resection, if safely possible, should be the goal of surgery since this results in the best rates of local control. Although various approaches exist to access the lateral ventricular system, selection of the optimal approach should be individualized to the patient based upon the location of the tumor within the ventricle, the tumor size, the origin of the vascular supply to the tumor, and the relationship to neighboring neurovascular structures at risk. In this operative video manuscript, the author demonstrates an illustrative step-by-step technique for microsurgical resection of a giant intraventricular meningioma of the left atrium via a transcortical parieto-occipital approach. The patient illustrated in this video presented with a large recurrent meningioma (> 5 cm) approximately 10 years after the initial resection. The tumor had grown around a pre-existing shunt catheter and resulted in loculated hydrocephalus. A complete resection and shunt revision were both performed at the same sitting. The operative technique and surgical nuances, including the surgical approach, intradural tumor removal, closure, and management of hydrocephalus are illustrated in this video atlas. The video can be found here: http://youtu.be/vpdmZ1ccWSM. (http://thejns.org/doi/abs/10.3171/2013.V1.FOCUS12352) PMID:23282155

  9. Prostate carcinoma mimicking a sphenoid wing meningioma

    PubMed Central

    Bradley, Lucas H.; Burton, Matthew; Gokden, Murat; Serletis, Demitre

    2015-01-01

    Introduction We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. Presentation of case An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Discussion Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). Conclusion We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. PMID:26318129

  10. Management of Intracranial Meningiomas Using Keyhole Techniques

    PubMed Central

    Burks, Joshua D; Conner, Andrew K; Bonney, Phillip A; Archer, Jacob B; Christensen, Blake; Smith, Jacqueline; Safavi-Abbasi, Sam

    2016-01-01

    Background: Keyhole craniotomies are increasingly being used for lesions of the skull base. Here we review our recent experience with these approaches for resection of intracranial meningiomas. Methods: Clinical and operative data were gathered on all patients treated with keyhole approaches by the senior author from January 2012 to June 2013. Thirty-one meningiomas were resected in 27 patients, including 9 supratentorial, 5 anterior fossa, 7 middle fossa, 6 posterior fossa, and 4 complex skull base tumors. Twenty-nine tumors were WHO Grade I, and 2 were Grade II.  Results: The mean operative time was 8 hours, 22 minutes (range, 2:55-16:14) for skull-base tumors, and 4 hours, 27 minutes (range, 1:45-7:13) for supratentorial tumors. Simpson Resection grades were as follows: Grade I = 8, II = 8, III = 1, IV = 15, V = 0. The median postoperative hospital stay was 4 days (range, 1-20 days). In the 9 patients presenting with some degree of visual loss, 7 saw improvement or complete resolution. In the 6 patients presenting with cranial nerve palsies, 4 experienced improvement or resolution of the deficit postoperatively. Four patients experienced new neurologic deficits, all of which were improved or resolved at the time of the last follow-up. Technical aspects and surgical nuances of these approaches for management of intracranial meningiomas are discussed.  Conclusions: With careful preoperative evaluation, keyhole approaches can be utilized singly or in combination to manage meningiomas in a wide variety of locations with satisfactory results. PMID:27284496

  11. Resection of meningiomas with implantable microwave coagulation

    SciTech Connect

    Zhou, X.P.; Xie, Q.L.; Liu, J.M.; Yue, Z.J.; Cai, K.H.

    1996-05-01

    Implantable microwave coagulation was used to perform resection on 62 patients that had intracranial meningiomas. When 20--60 W microwave power was applied for 15 s, the temperature at the center of the tumor tissue was 43--63 C; 30 mm from the center, the temperature was under 40 C. Histological changes in the center of the tumor showed coagulative necrosis, diminished nuclei, and obliterated blood vessels. The changes at 10--20 mm from the center of the tumor showed coagulative necrosis and degeneration and, 30--50 mm from the center of the tumor, showed normal cell morphology after microwave coagulation. The thermal field in brain tumor has an effective diameter of about 40 mm. No side effects on the normal brain tissues were observed. The amount of blood loss during the operation was minimal while the meningioma was coagulated, especially when the meningioma was located at the skull base or in the parasagittal or cerebral convexity region. After microwave coagulation, the entire tumor could easily be removed. Among the 62 surgically treated cases, gross total tumor excision was 85%. No postoperative complications occurred after microwave coagulation, and there was no operative mortality in the series. The authors believe that this new technique has the advantage of simplicity, less blood loss, and smooth postoperative procedures. Hemostatic effects during the operation are satisfactory, and blood transfusion can be reduced by 50--60%.

  12. Clinical manifestations of cerebellar disease.

    PubMed

    Javalkar, Vijayakumar; Khan, Misbba; Davis, Debra E

    2014-11-01

    Clinical manifestations of cerebellar disease include ataxia and tremor, as well as nystagmus, dysarthria, and cognitive dysfunction. Recognition of the cerebellar pattern of disease can aid in the prompt and correct diagnosis and lead to appropriate treatment and rehabilitation to minimize disability. PMID:25439285

  13. Variants of meningiomas: a review of imaging findings and clinical features.

    PubMed

    Kunimatsu, Akira; Kunimatsu, Natsuko; Kamiya, Kouhei; Katsura, Masaki; Mori, Harushi; Ohtomo, Kuni

    2016-07-01

    Meningiomas are common neoplasms that frequently occur in the brain and spine. Among the 15 histological subtypes of meningiomas in the WHO classification, the incidence of meningothelial meningiomas is the highest, followed by fibrous and transitional meningiomas. These three subtypes account for approximately 80 % of all meningiomas, and thus could be regarded as typical meningiomas. For this reason, other uncommon histological subtypes may be considered as imaging variants, and diagnosis is often challenging for radiologists solely based on imaging features of typical meningiomas. In addition to the histological subtypes, meningiomas arising in atypical locations could be easily mistaken for other lesions more commonly observed in those locations. The purpose of this article is to review characteristic clinical and imaging findings of uncommon meningiomas, including histological variants and meningiomas occurring in relatively rare locations. PMID:27138052

  14. Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas.

    PubMed

    Rossmeisl, J H; Robertson, J L; Zimmerman, K L; Higgins, M A; Geiger, D A

    2009-09-01

    Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis. PMID:19691646

  15. Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease.

    PubMed

    Yang, Zhen; Ye, Chuyang; Bogovic, John A; Carass, Aaron; Jedynak, Bruno M; Ying, Sarah H; Prince, Jerry L

    2016-02-15

    The cerebellum plays an important role in both motor control and cognitive function. Cerebellar function is topographically organized and diseases that affect specific parts of the cerebellum are associated with specific patterns of symptoms. Accordingly, delineation and quantification of cerebellar sub-regions from magnetic resonance images are important in the study of cerebellar atrophy and associated functional losses. This paper describes an automated cerebellar lobule segmentation method based on a graph cut segmentation framework. Results from multi-atlas labeling and tissue classification contribute to the region terms in the graph cut energy function and boundary classification contributes to the boundary term in the energy function. A cerebellar parcellation is achieved by minimizing the energy function using the α-expansion technique. The proposed method was evaluated using a leave-one-out cross-validation on 15 subjects including both healthy controls and patients with cerebellar diseases. Based on reported Dice coefficients, the proposed method outperforms two state-of-the-art methods. The proposed method was then applied to 77 subjects to study the region-specific cerebellar structural differences in three spinocerebellar ataxia (SCA) genetic subtypes. Quantitative analysis of the lobule volumes shows distinct patterns of volume changes associated with different SCA subtypes consistent with known patterns of atrophy in these genetic subtypes. PMID:26408861

  16. Autosomal recessive cerebellar ataxias

    PubMed Central

    Palau, Francesc; Espinós, Carmen

    2006-01-01

    Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

  17. Speech prosody in cerebellar ataxia

    NASA Astrophysics Data System (ADS)

    Casper, Maureen

    The present study sought an acoustic signature for the speech disturbance recognized in cerebellar degeneration. Magnetic resonance imaging was used for a radiological rating of cerebellar involvement in six cerebellar ataxic dysarthric speakers. Acoustic measures of the [pap] syllables in contrastive prosodic conditions and of normal vs. brain-damaged patients were used to further our understanding both of the speech degeneration that accompanies cerebellar pathology and of speech motor control and movement in general. Pair-wise comparisons of the prosodic conditions within the normal group showed statistically significant differences for four prosodic contrasts. For three of the four contrasts analyzed, the normal speakers showed both longer durations and higher formant and fundamental frequency values in the more prominent first condition of the contrast. The acoustic measures of the normal prosodic contrast values were then used as a model to measure the degree of speech deterioration for individual cerebellar subjects. This estimate of speech deterioration as determined by individual differences between cerebellar and normal subjects' acoustic values of the four prosodic contrasts was used in correlation analyses with MRI ratings. Moderate correlations between speech deterioration and cerebellar atrophy were found in the measures of syllable duration and f0. A strong negative correlation was found for F1. Moreover, the normal model presented by these acoustic data allows for a description of the flexibility of task- oriented behavior in normal speech motor control. These data challenge spatio-temporal theory which explains movement as an artifact of time wherein longer durations predict more extreme movements and give further evidence for gestural internal dynamics of movement in which time emerges from articulatory events rather than dictating those events. This model provides a sensitive index of cerebellar pathology with quantitative acoustic

  18. High incidence of meningioma among Hiroshima atomic bomb survivors.

    PubMed

    Shintani, T; Hayakawa, N; Hoshi, M; Sumida, M; Kurisu, K; Oki, S; Kodama, Y; Kajikawa, H; Inai, K; Kamada, N

    1999-03-01

    Since the atomic bomb explosions in Hiroshima and Nagasaki, high incidences of leukemia, thyroid cancer and other tumors have been reported as atomic bomb-induced tumors. We investigated the incidence of meningioma among Hiroshima atomic bomb survivors. Sixty-eight patients surgically treated for meningioma who had been within 2.0 km of the hypocenter of the explosion were identified. Six hundred and seven non-exposed patients with meningioma were also studied. Treatment dates were from 1975 to 1992. The incidences of meningioma among 68 subjects within 2.0 km and 607 non-exposed patients were 8.7 and 3.0 cases per 10(5) persons per year, respectively. The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively. The incidences of meningioma classified by distances from the hypocenter of 1.5-2.0 km, 1.0-1.5 km and less than 1.0 km were 6.3, 7.6 and 20.0, respectively. The incidences of meningioma classified by doses to the brain of 0-0.099 Sv, 0.1-0.99 Sv and more than 1.0 Sv were 7.7, 9.2 and 18.2, respectively. The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima. PMID:10408177

  19. Embolized meningiomas: risk of overgrading and neo-angiogenesis.

    PubMed

    Barresi, Valeria; Branca, Giovanni; Granata, Francesca; Alafaci, Concetta; Caffo, Maria; Tuccari, Giovanni

    2013-06-01

    Pre-operative embolization (POE) of meningiomas may induce histological changes which simulate malignancy, possibly resulting in overgrading. Aims of the present study were to identify clues to distinguish malignancy-related features from POE-related changes and to test for overgrading the grading scheme currently in use, in embolized meningiomas. In addition, we aimed to analyze whether the POE procedure may stimulate neo-angiogenesis in meningiomas. The histological features of a series of embolized meningiomas were evaluated and considered for grading assessment. In the same cases neo-angiogenesis was quantified by the evaluation of microvessel density (MVD) and correlated with the interval between POE and surgery. Necrosis and macronucleoli represented common findings in embolized meningiomas. Nonetheless, in most of the cases, necrosis showed an abrupt line of demarcation from the viable tumour tissue, and macronucleoli were restricted to peri-necrotic areas. Suggesting that these were POE-associated changes, exclusion of necrotic areas with an abrupt line of transition and focal macronucleoli from grading assessment resulted in increased specificity and positive predictive value in the identification of recurring meningiomas. In our cohort, MVD significantly increased with the time between POE and surgery, suggesting that POE procedure may induce neo-angiogenesis in meningiomas. In conclusion, a risk of overgrading there exists in embolized meningiomas, as a consequence of the frequent evidence of necrosis and prominent nucleoli in these tumours. In order to avoid overgrading, we suggest that necrosis showing an abrupt line of demarcation and focal peri-necrotic macronucleoli are not included in grading assessment. Also, caution should be used in the interpretation of MVD as a prognostic factor in embolized meningioma, as it may also result from POE procedure. PMID:23504284

  20. Endoscopic Endonasal Approach for Removal of Tuberculum Sellae Meningiomas.

    PubMed

    Ditzel Filho, Leo F S; Prevedello, Daniel M; Jamshidi, Ali O; Dolci, Ricardo L; Kerr, Edward E; Campbell, Raewyn; Otto, Bradley A; Carrau, Ricardo L; Kassam, Amin

    2015-07-01

    Tuberculum sellae meningiomas are challenging lesions; their critical location and often insidious growth rate enables significant distortion of the superjacent optic apparatus before the patient notices any visual impairment. This article describes the technical nuances, selection criteria and complication avoidance strategies for the endonasal resection of tuberculum sellae meningiomas. A stepwise description of the surgical technique is presented; indications, adjuvant technologies, pitfalls and the relevant anatomy are also reviewed. Tuberculum sellae meningiomas may be safely and effectively resected through the endonasal route; invasion of the optic canals does not represent a limitation. PMID:26141355

  1. Dorsal extradural meningioma: Case report and literature review

    PubMed Central

    Dehcordi, Soheila Raysi; Ricci, Alessandro; Chiominto, Alessandro; De Paulis, Danilo; Di Vitantonio, Hambra; Galzio, Renato J.

    2016-01-01

    Background: Extradural spinal mass lesions are most commonly metastatic tumors. Extradural meningiomas are rare, accounting for approximately 2.5–3.5% of spinal meningiomas; intraoperatively, they are easily mistaken for malignant tumors, especially in the en plaque variety, resulting in inadequate surgical treatment. Case Description: Our case is one of the first to describe a patient with two purely extradural meningiomas, one each between D3–D4 and between D5–D6 vertebral levels. Surgical resection was radical, and pathologically both lesions were meningothelialmeningiomas. Conclusions: Reviewing the literature, we discuss the pathogenesis, treatment strategies, and long-term behavior of these uncommon lesions.

  2. Foramen Magnum Meningioma: a Case Report and Review of Literature

    PubMed Central

    Jurinovic, Pavao; Bulicic, Ana Repic; Marcic, Marino; Mise, Nikolina Ivica; Titlic, Marina; Suljic, Enra

    2016-01-01

    Introduction: Meningiomas are slow-growing benign tumors that arise at any location where arachnoid cells reside. Although meningiomas account for a sizable proportion of all primary intracranial neoplasms (14.3–19%), only 1.8 to 3.2% arise at the foramen magnum. Their indolent development at the craniocervical junction makes clinical diagnosis complex and often leads to a long interval between onset of symptoms and diagnosis. Case report: We report a case of a 79-year-old male patient, presented with ataxia and sense of threatening fainting during verticalization. Magnetic resonance imaging revealed the presence of meningioma in the right side of craniospinal junction. PMID:27041817

  3. Dural lucent line: characteristic sign of hyperostosing meningioma en plaque

    SciTech Connect

    Kim, K.S.; Rogers, L.F.; Lee, C.

    1983-12-01

    Hyperostosis of the skull associated with en plaque form of meningioma may present a diagnostic challenge, since the intracranial part of the tumor is not visualized by skull radiography, computed tomography (CT), or other neuroradiologic methods. The authors report four cases of hyperostosing meningioma en plaque demonstrating a characteristic feature: a subdural layer of ossification along the hyperostotic bone with a dural lucent interface. Polytomography or high-resolution CT at bone window settings is necessary to identify the dural lucent line. The absence of this sign does not exclude meningioma en plaque.

  4. Cystic change in primary paediatric optic nerve sheath meningioma.

    PubMed

    Narayan, Daniel; Rajak, Saul; Patel, Sandy; Selva, Dinesh

    2016-08-01

    Primary optic nerve sheath meningiomas (PONSM) are rare in children. Cystic meningiomas are an uncommon subgroup of meningiomas. We report a case of paediatric PONSM managed using observation alone that underwent cystic change and radiological regression. A 5-year-old girl presented with visual impairment and proptosis. Magnetic resonance (MR) imaging demonstrated a PONSM. The patient was left untreated and followed up with regular MR imaging. Repeat imaging at 16 years of age showed the tumour had started to develop cystic change. Repeat imaging at 21 years of age showed the tumour had decreased in size. PMID:27310300

  5. Expression and gene doses changes of the p53-regulator PPM1D in meningiomas: a role in meningioma progression?

    PubMed

    Fukami, Shinjiro; Riemenschneider, Markus J; Kohno, Michihiro; Steiger, Hans Jakob

    2016-07-01

    The aim of our study was to clarify the expression and gene copy number levels of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D), which is thought to be a regulator of the p53 protein in meningiomas of all three different WHO grades. Genomic DNA and mRNA were extracted from frozen tissues of meningiomas (WHO grade I, 20 cases; grade II, 17 cases; grade III, 20 cases). For analysis of the mRNA expression and gene dosage level of PPM1D, semiquantitative duplex RT-PCR, real-time RT-PCR, and semiquantitative duplex PCR were performed. We also analyzed several genes which locate near PPM1D in the genomic locus 17q22-24 using semiquantitative duplex RT-PCR. We found that the mean mRNA expression of PPM1D is higher in WHO grade II and III meningiomas than in grade I tumors. This finding is accompanied by moderate gene dosage increases for PPM1D in meningiomas of higher grades. Other genes located in the vicinity of PPM1D also showed mRNA overexpression in single meningioma cases. For these genes, however, no significant expression differences between meningioma grades could be observed. Thus, PPM1D in the chromosomal location 17q22-24 might be the most relevant candidate gene with respect to a potential functional implication in meningioma progression. PMID:26942600

  6. Peritumoral cystic meningioma: A report of two cases and review of the literature

    PubMed Central

    WANG, PENGFEI; HAN, SONG; LIU, NING; YU, CHUNJIANG; QI, XUELING; ZHU, MINGWANG; ZHANG, XIANGQIAN; WANG, LI; YAN, CHANGXIANG

    2016-01-01

    The present study reported two cases of cystic meningioma. The clinical manifestations, magnetic resonance imaging (MRI) scan and histological aspects of the lesion and the associated cyst were examined. The classification of cystic meningioma was also discussed. The present study focused on the formation, diagnosis and management of the peritumoral cystic meningioma, and aimed to clarify certain contradictions in the literature concerning the formation of the peritumoral cyst meningioma: MRI alone is inadequate to determine the type of cystic meningioma, or to identify neoplastic cells on the cystic wall. In conclusion, surgical removal of the entire cyst is recommended in peritumoral cyst meningioma. PMID:26998010

  7. Foster Kennedy Syndrome Due to Meningioma Growth during Pregnancy

    PubMed Central

    Rodríguez-Porcel, Federico; Hughes, Ian; Anderson, Douglas; Lee, John; Biller, José

    2013-01-01

    Tumors of the olfactory groove may cause unilateral optic atrophy with contralateral papilledema and anosmia (Foster Kennedy syndrome). We describe a case of a young pregnant woman with Foster Kennedy syndrome due to an olfactory groove meningioma. PMID:24273529

  8. Short communication: sclerosing meningioma in the deep sylvian fissure.

    PubMed

    Fukushima, Shintaro; Narita, Yoshitaka; Yonezawa, Motoki; Ohno, Makoto; Arita, Hideyuki; Miyakita, Yasuji; Ichimura, Koichi; Yoshida, Akihiko; Shibui, Soichiro

    2014-10-01

    Sclerosing meningioma is a rare type of meningeal tumor with extensive collagen depositions. Deep sylvian meningioma, a tumor that is unattached to the dura mater, is also unusual. The biological activity of both is controversial, as are therapeutic strategies. A heterogeneous contrast-enhanced mass in the right sylvian fissure of a 10-year-old boy with a 3-year history of epilepsy was identified via magnetic resonance imaging. The patient underwent partial surgical resection because the tumor was hard and contained numerous perforators arising from the right middle cerebral artery. The tumor was histologically diagnosed as sclerosing meningioma. Twelve months after surgery, the patient was asymptomatic and did not require any additional therapies. This case is the first report of a sclerosing meningioma arising in the deep sylvian fissure. We discuss the therapeutic dilemma of this case with respect to the current literature. PMID:24141724

  9. Open Heart Surgery with Intracranial Meningioma: Case Report & Literature Review.

    PubMed

    Ahmad, Munir; Al-Arifi, Ahmed; Najm, Hani K

    2015-07-01

    Meningiomas are generally considered slow growing tumours of arachnoid cell origin which remain asymptomatic for a long period of time and are usually managed conservatively by serial radiological follow-up. Only those lesions which show a potential for rapid growth are considered for surgical resection. Coronary artery bypass surgery usually involves use of cardiopulmonary bypass which incites varying degrees of systemic inflammatory response. Although some meningiomas are recognised by secretion of vasoactive substances leading to peri-lesion oedema, very little is known about the behaviour of asymptomatic meningiomas during a normal run of cardiopulmonary bypass where there is a significant rise in the plasma level of many vasoactive substances. We report the case of a 68 year-old male patient with asymptomatic meningioma who required urgent coronary artery bypass surgery leading to peri-lesion oedema and significant post-operative morbidity due to reversible neurological deficit. PMID:25843223

  10. [Meningioma: management of the most common brain tumour].

    PubMed

    Hundsberger, Thomas; Surbeck, Werner; Hader, Claudia; Putora, Paul Martin; Conen, Katrin; Roelcke, Ulrich

    2016-04-13

    Meningiomas are the most common primary brain tumours in adults and are therefore relevant for general practitioners. Most meningiomas are benign and neurosurgical resection offers the best chance of cure. However, complete resection is not achievable in many patients. This accounts for a relevant rate of tumour recurrences within 15 years of follow up. In atypical and anaplastic meningiomas of WHO grade II and III time to recurrence is dramatically shorter and these tumours need multimodal treatment strategies including postoperative radiotherapy. Various systemic treatments have occasionally been used as salvage therapy, but were essentially not effective. Only recently, Sunitinib, a small thyrosine kinase inhibitor as well as bevacizumab, a therapeutic antibody, have shown more promising results in highly pretreated, refractory meningioma patients. PMID:27078728

  11. SMARCE1 mutations in pediatric clear cell meningioma: case report.

    PubMed

    Evans, Linton T; Van Hoff, Jack; Hickey, William F; Smith, Miriam J; Evans, D Gareth; Newman, William G; Bauer, David F

    2015-09-01

    Clear cell meningioma (CCM) is an uncommon variant of meningioma. The authors describe a case of a pediatric CCM localized to the lumbar spine. After resection, sequencing revealed an inactivating mutation in the SWI/SNF chromatin remodeling complex subunit SMARCE1, with loss of the second allele in the tumor. The authors present a literature review of this mutation that is associated with CCM and a family history of spine tumors. PMID:26114992

  12. Temporal bone meningioma involving the middle ear: A case report

    PubMed Central

    RICCIARDIELLO, FILIPPO; FATTORE, LUCIA; LIGUORI, MARIA ESTER; OLIVA, FLAVIA; LUCE, AMALIA; ABATE, TERESA; CARAGLIA, MICHELE; PIANESE, ANNALISA; RAUCCI, ALDO FALCO

    2015-01-01

    Meningioma is a common intracranial tumor involving the meninges. The localization of this type of tumor is rarely extracranial due to its typically low invasive properties. Furthermore, invasion of the middle ear is exceptional. The present study reported a case of meningioma extending into the middle ear from the middle cranial fossa through the tegmen tympani. The clinical and pathological characteristics, as well as the outcome of the patient, were described. PMID:26622828

  13. [Spinal extradural meningiomas: MRI findings in two cases].

    PubMed

    Vargas, M I; Abu Eid, M; Bogorin, A; Beltechi, R; Boyer, P; Javier, R M; Zöllner, G; Dietemann, J L

    2004-06-01

    Spinal extradural meningiomas are rare and may be easily confused with malignant neoplasms. We report two unusual cases of epidural spinal meningioma one within the left C6-C7 foramen and the other within the left posterolateral epidural space at the T3-T4 level. Low signal intensity of the tumor on T2-wi, thickening and enhancement of the dura with only the possibility of bone erosion are the most characteristic MR findings. PMID:15356447

  14. Speech prosody in cerebellar ataxia.

    PubMed

    Casper, Maureen A; Raphael, Lawrence J; Harris, Katherine S; Geibel, Jennifer M

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy speakers and six with ataxia. The speaking task was designed to elicit six different prosodic conditions and four contrastive prosodic events. Distinct prosodic patterns were elicited by the examiner for cerebellar patients and healthy speakers. These utterances were digitally recorded and analysed acoustically and statistically. The healthy speakers showed statistically significant differences among all four prosodic contrasts. The normal model described by the prosodic contrasts provided a sensitive index of cerebellar pathology with quantitative acoustic analyses. A significant interaction between subject groups and prosodic conditions revealed a compromised prosody in cerebellar patients. Significant differences were found for durational parameters, F0 and formant frequencies. The cerebellar speakers demonstrated different patterns of syllable lengthening and syllable reduction from that of the healthy speakers. PMID:17613097

  15. Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5

    PubMed Central

    Abedalthagafi, Malak S.; Merrill, Parker H.; Bi, Wenya Linda; Jones, Robert T.; Listewnik, Marc L.; Ramkissoon, Shakti H.; Thorner, Aaron R.; Dunn, Ian F.; Beroukhim, Rameen; Alexander, Brian M.; Brastianos, Priscilla K.; Francis, Joshua M.; Folkerth, Rebecca D.; Ligon, Keith L.; Hummelen, Paul Van; Ligon, Azra H.; Santagata, Sandro

    2014-01-01

    Meningiomas are a diverse group of tumors with a broad spectrum of histologic features. There are over 12 variants of meningioma, whose genetic features are just beginning to be described. Angiomatous meningioma is a World Health Organization (WHO) meningioma variant with a predominance of blood vessels. They are uncommon and confirming the histopathologic classification can be challenging. Given a lack of biomarkers that define the angiomatous subtype and limited understanding of the genetic changes underlying its tumorigenesis, we compared the genomic characteristics of angiomatous meningioma to more common meningioma subtypes. While typical grade I meningiomas demonstrate monosomy of chromosome 22 or lack copy number aberrations, 13 of 14 cases of angiomatous meningioma demonstrated a distinct copy number profile – polysomies of at least one chromosome, but often of many, especially in chromosomes 5, 13, and 20. WHO grade II atypical meningiomas with angiomatous features have both polysomies and genetic aberrations characteristic of other atypical meningiomas. Sequencing of over 560 cancer-relevant genes in 16 cases of angiomatous meningioma showed that these tumors lack common mutations found in other variants of meningioma. Our study demonstrates that angiomatous meningiomas have distinct genomic features that may be clinically useful for their diagnosis. PMID:25347344

  16. Molecular heterogeneity of meningioma with INI1 mutation

    PubMed Central

    Rieske, P; Zakrzewska, M; Piaskowski, S; Jaskólski, D; Sikorska, B; Papierz, W; Zakrzewski, K; Liberski, P P

    2003-01-01

    Background: INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported. Aims: To analyse the INI1 gene in meningioma. Methods: Exons 1, 4, 5, and 9 of the INI1 gene were analysed by the polymerase chain reaction and direct sequencing in 80 meningiomas. For all cases, western blotting of the INI1 protein was performed. Results: Only one of the 80 samples showed a cytosine insertion in codon 376. This mutation changed the open reading frame in almost the whole exon 9 and resulted in a longer hSNF5 protein. Complex analysis of the above described tumour sample by western blotting, DNA sequencing, and loss of heterozygosity (LOH) analysis showed that this particular meningioma consisted of heterogeneic cellular components. One of these components had a mutated INI1 gene, whereas in the other component INI1 was intact. Conclusions: INI1 mutation is a rare event in the molecular pathology of meningiomas. It is possible for the INI1 gene to be mutated in only a proportion of meningioma cells. PMID:14514925

  17. EANO guidelines for the diagnosis and treatment of meningiomas.

    PubMed

    Goldbrunner, Roland; Minniti, Giuseppe; Preusser, Matthias; Jenkinson, Michael D; Sallabanda, Kita; Houdart, Emmanuel; von Deimling, Andreas; Stavrinou, Pantelis; Lefranc, Florence; Lund-Johansen, Morten; Moyal, Elizabeth Cohen-Jonathan; Brandsma, Dieta; Henriksson, Roger; Soffietti, Riccardo; Weller, Michael

    2016-09-01

    Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades. PMID:27599143

  18. Hidden association of Cowden syndrome, PTEN mutation and meningioma frequency

    PubMed Central

    Yakubov, Eduard; Ghoochani, Ali; Buslei, Rolf; Buchfelder, Michael; Eyüpoglu, Ilker Y.; Savaskan, Nicolai

    2016-01-01

    Cowden syndrome (CS) is clinically presented by multiple hamartomas, often with mucocutaneous lesions, goiter, breast cancer and gastrointestinal polyps. CS is a genetic disorder of autosomal dominant inheritance and is one distinct syndrome of the phosphatase and tensin homolog on chromosome 10 (PTEN) hamartoma tumor spectrum. Noteworthy, PTEN germline mutations are related to a wide range of brain tumors. We performed a systematic analysis and review of the medical literature for Cowden syndrome and meningioma and additionally present the case of a 29-year- old CS patient diagnosed with multiple meningiomas. We found strong evidence for high incidence of brain tumors in CS patients. In particular meningiomas and gangliocytomas/Lhermitte-Duclos disease were often associated with 8% and 9% respectively in CS patients. Since aberrations in chromosome 10q are associated with meningiomas, it is likely that the underlying mutations in CS drive to a certain extent neoplastic meningioma growth. We propose to include meningiomas and brain tumors in the major criteria spectrum of CS-related disorders. This could warrant early diagnosis of brain lesions and close therapy, as well as better monitoring of patients with CS. PMID:27489861

  19. Histological and immunohistochemical study of 30 cases of canine meningioma.

    PubMed

    Montoliu, P; Añor, S; Vidal, E; Pumarola, M

    2006-11-01

    This report describes the incidence, location and histopathological and immunohistochemical features of 30 canine meningiomas, of which 22 were intracranial, three were retrobulbar and five were located in the spinal canal. Nine types of meningioma were diagnosed: transitional (9), meningothelial (5), psammomatous (3), anaplastic (3), fibroblastic (2), angioblastic (2), papillary (2), microcystic (1) and meningiomas arising from the optic nerve (3). One of the optic nerve tumours had a granular cell component. All tumours were examined immunohistochemically with antibodies against vimentin, S100, neuron-specific enolase (NSE), cytokeratin (CK) and glial fibrillary acidic protein (GFAP). Vimentin was demonstrated in all tumours, and concentric whorls of cells showed more intense labelling than did bundles of fibroblastic cells. S100 labelling was detected in all tumours except a single angioblastic meningioma. The intensity of labelling for S100 was lower than that for vimentin, and bundles of fibroblastic cells showed particularly strong positivity. NSE labelling was highly variable, but most tumours displayed moderate positivity. CK expression was observed in five of the 30 meningiomas, and was stronger in areas of microcystic differentiation. Most of the tumours were GFAP-negative, but two fibroblastic meningiomas were strongly positive. PMID:17049358

  20. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Synonym(s): ... Publications and Information Publicaciones en Español What are Ataxias and Cerebellar or Spinocerebellar Degeneration? Ataxia often occurs ...

  1. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  2. Canine intracranial meningiomas: Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers.

    PubMed

    Font, Cristina; de la Fuente, Cristian; Pumarola, Martí; Blasco, Ester; Fernández, Francisco; Viu, Judit; Añor, Sònia

    2015-12-01

    The haemostatic system influences angiogenesis, cell growth and metastasis in solid tumours. The aim of this study was to investigate tissue factor (TF) expression, fibrin/fibrinogen and D-dimer deposition, as well as the occurrence of intravascular thrombosis (IVT) in canine intracranial meningiomas using immunohistochemistry. All but three (26/29) meningiomas expressed TF. TF immunolabelling was significantly higher in high-grade (grades II and III) than in low-grade (grade I) meningiomas. Fibrin/fibrinogen and D-dimer deposits were detected in all meningiomas and staining scores were statistically different between different meningioma grades. IVT was detected in 19/29 specimens, but no statistical differences were observed between different malignancy grades. In conclusion, the haemostatic system may be involved in meningioma pathobiology and may be a potential therapeutic target for canine meningiomas, as also suggested for human meningiomas. PMID:26526524

  3. Early adjuvant radiotherapy in the treatment of atypical meningioma.

    PubMed

    Jenkinson, Michael D; Waqar, Mueez; Farah, Jibril Osman; Farrell, Michael; Barbagallo, Giuseppe M V; McManus, Robin; Looby, Seamus; Hussey, Deirdre; Fitzpatrick, David; Certo, Francesco; Javadpour, Mohsen

    2016-06-01

    Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned. PMID:26775147

  4. Proton Stereotactic Radiosurgery for the Treatment of Benign Meningiomas

    SciTech Connect

    Halasz, Lia M.; Bussiere, Marc R.; Dennis, Elizabeth R.; Niemierko, Andrzej; Chapman, Paul H.; Loeffler, Jay S.; Shih, Helen A.

    2011-12-01

    Purpose: Given the excellent prognosis for patients with benign meningiomas, treatment strategies to minimize late effects are important. One strategy is proton radiation therapy (RT), which allows less integral dose to normal tissue and greater homogeneity than photon RT. Here, we report the first series of proton stereotactic radiosurgery (SRS) used for the treatment of meningiomas. Methods and Materials: We identified 50 patients with 51 histologically proven or image- defined, presumed-benign meningiomas treated at our institution between 1996 and 2007. Tumors of <4 cm in diameter and located {>=}2 mm from the optic apparatus were eligible for treatment. Indications included primary treatment (n = 32), residual tumor following surgery (n = 8), and recurrent tumor following surgery (n = 10). The median dose delivered was 13 Gray radiobiologic equivalent (Gy[RBE]) (range, 10.0-15.5 Gy[RBE]) prescribed to the 90% isodose line. Results: Median follow-up was 32 months (range, 6-133 months). Magnetic resonance imaging at the most recent follow-up or time of progression revealed 33 meningiomas with stable sizes, 13 meningiomas with decreased size, and 5 meningiomas with increased size. The 3-year actuarial tumor control rate was 94% (95% confidence interval, 77%-98%). Symptoms were improved in 47% (16/ 34) of patients, unchanged in 44% (15/34) of patients, and worse in 9% (3/34) of patients. The rate of potential permanent adverse effects after SRS was 5.9% (3/51 patients). Conclusions: Proton SRS is an effective therapy for small benign meningiomas, with a potentially lower rate of long-term treatment-related morbidity. Longer follow-up is needed to assess durability of tumor control and late effects.

  5. p38MAPK activation and DUSP10 expression in meningiomas.

    PubMed

    Johnson, Mahlon D; Reeder, Jay E; O'Connell, Mary

    2016-08-01

    The mitogen activated protein kinase (MAPK) p38MAPK has been implicated in regulation of cell proliferation and apoptosis. However, expression, activation and regulation has not been studied in meningiomas, to our knowledge. p38MAPK is regulated, in part, by dual specificity phosphatases (DUSP) that inactivate signaling by dephosphorylation. DUSP10 is also a likely participant in regulating meningioma proliferation. Five fetal and an adult human leptomeninges and 37 meningioma cultures (MC) were evaluated for DUSP10 as well as phosphorylation of its substrates p38MAPK and p44/42MAPK by western blot and DUSP10 expression by polymerase chain reaction. Platelet derived growth factor-BB (PDGF-BB), transforming growth factor B1 (TGFB1) and cerebrospinal fluid effects on DUSP10 and signaling were also studied in vitro. DUSP10 and phospho-p38MAPK and phospho-p44/42MAPK were detected in all six leptomeninges. DUSP10 was detected in 13 of 17 World Health Organization grade I, 11 of 14 grade II and four of six grade III meningiomas. Phospho-p38MAPK was detected in nine of 17 grade I, two of six grade II, and four of six grade III meningiomas. In the majority of meningiomas DUSP10 expression correlated inversely with phosphorylation of p38MAPK. PDGF-BB increased DUSP10 in MC2 and MC4 and weakly in MC3. TGFB1 increased phosphorylation of p38MAPK and caspase 3 activation. Thus p38MAPK and DUSP10 likely participate in the pathogenesis of meningiomas. PMID:27050915

  6. Radiation-induced anaplastic ependymoma mimicking a skull base meningioma: A case report

    PubMed Central

    SPALLONE, ALDO; MARCHIONE, PASQUALE; DI CAPUA, MARIO; BELVISI, DANIELE

    2016-01-01

    The present study describes the case of a 63-year-old woman presenting with headache, dizziness and vomiting due to a an ovoid mass in the left pre-bulbar cistern, apparently arising from the lower clivus and the foramen magnum. The clinical history revealed the subtotal removal of a right cerebellar low-grade glioma 15 years previously and subsequent conventional 60-Gy radiotherapy. Notably, following gross total resection, histopathological examination showed microscopic features that resulted in a diagnosis of anaplastic ependymoma. The patient underwent surgery to remove the mass and post-operative chemotherapy with temozolomide. A progressive improvement of neurological signs and symptoms was observed during the postoperative course. At the 6-month follow-up, the patient was free from clinical and radiological recurrence. The unusual features of this rare secondary brain tumor were the extrassial location in the posterior fossa, the unusual age-associated location of the histological subtype and the fact that it closely mimicked a skull-base meningioma. PMID:26893630

  7. [Clinical manifestations of cerebellar ataxias].

    PubMed

    Abdulkerimov, Kh T

    2003-01-01

    The analysis of clinical manifestations and focal symptoms in 18 patients with cerebellar ataxia (CA) has shown that these markers are not sufficient for making an accurate diagnosis in all CA cases. It is recommended to verify an ataxia form with objective methods, computed stabilography, in particular. PMID:12958853

  8. Orthostatic tremor: a cerebellar pathology?

    PubMed Central

    Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

    2016-01-01

    See Muthuraman et al. (doi:10.1093/aww164) for a scientific commentary on this article. Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects. PMID:27329770

  9. Speech Prosody in Cerebellar Ataxia

    ERIC Educational Resources Information Center

    Casper, Maureen A.; Raphael, Lawrence J.; Harris, Katherine S.; Geibel, Jennifer M.

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy…

  10. The compartmental restriction of cerebellar interneurons

    PubMed Central

    Consalez, G. Giacomo; Hawkes, Richard

    2013-01-01

    The Purkinje cells (PC's) of the cerebellar cortex are subdivided into multiple different molecular phenotypes that form an elaborate array of parasagittal stripes. This array serves as a scaffold around which afferent topography is organized. The ways in which cerebellar interneurons may be restricted by this scaffolding are less well-understood. This review begins with a brief survey of cerebellar topography. Next, it reviews the development of stripes in the cerebellum with a particular emphasis on the embryological origins of cerebellar interneurons. These data serve as a foundation to discuss the hypothesis that cerebellar compartment boundaries also restrict cerebellar interneurons, both excitatory [granule cells, unipolar brush cells (UBCs)] and inhibitory (e.g., Golgi cells, basket cells). Finally, it is proposed that the same PC scaffold that restricts afferent terminal fields to stripes may also act to organize cerebellar interneurons. PMID:23346049

  11. Birth desires and intentions of women diagnosed with a meningioma

    PubMed Central

    Owens, Michelle A.; Craig, Benjamin M.; Egan, Kathleen M.; Reed, Damon R.

    2015-01-01

    OBJECT To the authors’ knowledge, no previous study has examined the impact of meningioma diagnosis on women’s birth desires and intentions. In an exploratory study, the authors surveyed women affected by meningioma to determine their attitudes toward childbearing and the influences, including physician recommendations, on this major life decision and compared their responses to those of women in the general population. METHODS Meningioma survivors from the Meningioma Mommas online support group participated in an online survey that included questions on their birth desires and intentions, whether the risk of disease recurrence influenced their reproductive decisions, and risks communicated to them by their physicians. Using chi-square and rank-sum tests, the authors compared the survey participants’ responses with those of the general population as assessed by the 2006–2010 National Survey of Family Growth. Logistic regression was used to adjust for differences in age, race, ethnicity, education, parity, pregnancy status, and infertility status in these populations. RESULTS Respondents with meningioma were more likely than those in the general population to report wanting a baby (70% vs 54%, respectively), intending to have a baby (27% vs 12%, respectively), and being very sure about this intention (10% vs 2%, respectively). More than half (32 of 61) of the women of childbearing age reported being advised by a physician about potential risk factors for recurrence of the meningioma, and pregnancy was the most commonly cited risk factor (26 of 61). The most common factor influencing birth desires and intentions was risk of the meningioma returning and requiring more treatment, which was reported by nearly two-thirds of the women in their childbearing years. CONCLUSIONS A majority of the meningioma survivors of childbearing age who completed the survey reported a desire for children, although concern about the risk of meningioma recurrence was an important

  12. MS-31INTRACRANIAL MENINGIOMAS COMPLICATED BY HYPERTENSION: FOUR CASE REPORTS

    PubMed Central

    Zhen, Haining; Zhao, Wei; Yang, Xin; Wang, Jiang; Zhao, Jun; Huo, Junli; Zhang, Xiang; Fei, Zhou

    2014-01-01

    BACKGROUND: The etiology and mechanism of both meningioma and hypertension are still not fully understood, and their diagnosis and treatment still need to be improved. The phenomenon that some meningiomas can directly lead hypertension was never reported previously. Here we reported four consecutive cases with hypertension secondary to intracranial meningiomas. CASE PRESENTATION: Case 1 was a 62-year-old woman with a meningioma (size: about 2.0 cm × 1.6 cm × 1.5 cm) at left frontal lobe and with a medical history of hypertension for 10 years; Case 2 was a 50-year-old woman with a meningioma (size: about 1.5 cm × 1.2 cm × 1.1 cm) at right parietal lobe and with a medical history of hypertension for 4 years; Case 3 was a 42-year-old woman with a meningioma (size: about 2.7 cm × 2.6 cm × 2.3 cm) in trigonum of left lateral ventricle and with a medical history of hypertension for 3 months; Case 4 was a 56-year-old woman with a meningioma (size: about 2.0 cm × 1.8 cm × 1.5 cm) at bilateral falx of frontal lobe and with a medical history of hypertension for 8 years. All the four cases were treated in our hospital from April to June in 2013. After surgical resection of the tumors, blood pressure of all the patients returned to normal level in a short term, and it remained stable for 10 to 12 months of postoperative follow-up period. CONCLUSION: These four cases may present a new clinical syndrome and provide important clinical insights, and also should attract the attention of clinicians, i.e. in patients with hypertension, coexisting intracranial meningiomas should be suspected, and appropriate diagnosis and aggressive surgical treatment should be provided; for patients with hypertension secondary to meningiomas, their hypertension can be cured after surgical removal of the tumors.

  13. Crush Cytology of Secretory Meningioma: A Case Report

    PubMed Central

    Kim, Na Rae; Yee, Gie-Taek

    2015-01-01

    Secretory meningioma, a histologic subtype of meningioma of World Health Organization grade 1, is clinically significant because it is frequently accompanied by peritumoral brain edema. The patient was a 53-year-old woman suffering from dysarthria and motor weakness of the right arm. Enhanced magnetic resonance images showed an enhancing mass measuring 2.5 cm in size located in the right parietal convexity. Intraoperative squash cytology showed moderately cellular smears composed mainly of clusters of ovoid cells with scattered whorl formations. The cells had round nuclei and a moderate amount of eosinophilic cytoplasm with ill-defined cell borders. Neither atypia nor mitosis was observed. Some scattered round shaped eosinophilic refractile hyaline globules, measuring from 5 to 25 µm, were observed, and a periglobular halo was occasionally observed. The diagnosis of secretory meningioma should be made as early as possible so that neurosurgeons can prevent postoperative aggravation of peritumoral edema. We emphasize that cytologic findings including eosinophilic, non-fibrillary cytoplasm with eosinophilic refractile hyaline globules are helpful in differentiating secretory meningioma from other subtypes of meningioma, primary and metastatic brain tumors. PMID:26605274

  14. Meningiomas of the Pediatric Skull Base: A Review

    PubMed Central

    Gump, William C.

    2014-01-01

    Pediatric skull base meningiomas are rare and complex clinical entities. Meningioma is a relatively uncommon brain tumor in children, and only ∼ 27% involve the skull base. Some evidence suggests that these tumors are more likely to be atypical or malignant in children than adults. The absence of female preponderance in pediatric meningiomas is reflected in the skull base subpopulation. Skull base meningiomas in children are most likely to be found in the anterior or middle fossa base, or involving the orbit and optic nerve sheath. Petroclival, suprasellar/parasellar, cerebellopontine angle, cavernous sinus, and foramen magnum tumors are very rare. Meningiomas constitute a small proportion of reported cases of pediatric skull base pathology, and they are entirely absent from many case series. Initial gross total resection is consistently associated with superior outcomes. Surgical approaches to the pediatric skull base must take additional factors into consideration including relatively smaller anatomy, immature dentition, incompletely aerated sinuses and air cells, and altered configurations of structures such as the pterional bony complex. Multidisciplinary expertise is essential to optimizing treatment outcomes. PMID:25685652

  15. Spinal meningiomas: clinicoradiological factors predicting recurrence and functional outcome.

    PubMed

    Maiti, Tanmoy K; Bir, Shyamal C; Patra, Devi Prasad; Kalakoti, Piyush; Guthikonda, Bharat; Nanda, Anil

    2016-08-01

    OBJECTIVE Spinal meningiomas are benign tumors with a wide spectrum of clinical and radiological features at presentation. The authors analyzed multiple clinicoradiological factors to predict recurrence and functional outcome in a cohort with a mean follow-up of more than 4 years. The authors also discuss the results of clinical studies regarding spinal meningiomas in the last 15 years. METHODS The authors retrospectively reviewed the clinical and radiological details of patients who underwent surgery for spinal tumors between 2001 and 2015 that were histopathologically confirmed as meningiomas. Demographic parameters, such as age, sex, race, and association with neurofibromatosis Type 2, were considered. Radiological parameters, such as tumor size, signal changes of spinal cord, spinal level, number of levels, location of tumor attachment, shape of tumor, and presence of dural tail/calcification, were noted. These factors were analyzed to predict recurrence and functional outcome. Furthermore, a pooled analysis was performed from 13 reports of spinal meningiomas in the last 15 years. RESULTS A total of 38 patients were included in this study. Male sex and tumors with radiological evidence of a dural tail were associated with an increased risk of recurrence at a mean follow-up of 51.2 months. Ventral or ventrolateral location, large tumors, T2 cord signal changes, and poor preoperative functional status were associated with poor functional outcome at 1-year follow-up. CONCLUSIONS Spine surgeons must be aware of the natural history and risk factors of spinal meningiomas to establish a prognosis for their patients. PMID:27476848

  16. Anaplastic meningioma: octreotide therapy for a case of recurrent and progressive intracranial disease.

    PubMed

    Rammo, Richard; Rock, Adam; Transou, Andrea; Raghunathan, Aditya; Rock, Jack

    2016-02-01

    Meningiomas are common intracranial tumors categorized as Grades I-III per the current WHO guidelines. A small percentage of meningiomas are Grades II and III, which are likely to recur after initial treatment. Grade III meningiomas are considered to be malignant and warrant aggressive management. If surgery and radiation fail to produce lasting remission, effective treatment options for patients with progressive anaplastic meningiomas are elusive. The authors present the case of a patient with a meningioma that gradually progressed from Grade I to Grade III over 12 years despite repeated surgery and radiation therapy. The patient has been in remission for over 3 years following octreotide therapy. PMID:26274993

  17. Orbital roof intradiploic meningioma in a 16-year-old girl.

    PubMed

    Verma, Satish Kumar; Satyarthee, Gurudutta; Borkar, Sachin Anil; Singh, Manmohan; Sharma, Bhawani Shnakar

    2015-01-01

    Primary intraosseous or ectopic meningioma of the skull is a rare tumor accounting for about 1% of meningioma. Intradiploic meningioma is an extremely rare type of extraneuraxial meningiomas. Intradiploic meningioma of the orbit is extremely rare, and <8 such cases are reported till date in western literature occurring in the pediatric age group. Here the authors present a case of 16-year-old female, who presented with progressive proptosis, with normal vision and was managed successfully surgically. Clinical features, pathophysiology, and surgical management of this rare entity are discussed in the context of pertinent literature. PMID:25878746

  18. Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non-skull base meningiomas.

    PubMed

    Mansouri, Alireza; Klironomos, George; Taslimi, Shervin; Kilian, Alex; Gentili, Fred; Khan, Osaama H; Aldape, Kenneth; Zadeh, Gelareh

    2016-08-01

    OBJECTIVE The objective of this study was to identify the natural history and clinical predictors of postoperative recurrence of skull base and non-skull base meningiomas. METHODS The authors performed a retrospective hospital-based study of all patients with meningioma referred to their institution from September 1993 to January 2014. The cohort constituted both patients with a first-time presentation and those with evidence of recurrence. Kaplan-Meier curves were constructed for analysis of recurrence and differences were assessed using the log-rank test. Cox proportional hazard regression was used to identify potential predictors of recurrence. RESULTS Overall, 398 intracranial meningiomas were reviewed, including 269 (68%) non-skull base and 129 (32%) skull base meningiomas (median follow-up 30.2 months, interquartile range [IQR] 8.5-76 months). The 10-year recurrence-free survival rates for patients with gross-total resection (GTR) and subtotal resection (STR) were 90% and 43%, respectively. Skull base tumors were associated with a lower proliferation index (0.041 vs 0.062, p = 0.001), higher likelihood of WHO Grade I (85.3% vs 69.1%, p = 0.003), and younger patient age (55.2 vs 58.3 years, p = 0.01). Meningiomas in all locations demonstrated an average recurrence rate of 30% at 100 months of follow-up. Subsequently, the recurrence of skull base meningiomas plateaued whereas non-skull base lesions had an 80% recurrence rate at 230 months follow-up (p = 0.02). On univariate analysis, a prior history of recurrence (p < 0.001), initial WHO grade following resection (p < 0.001), and the inability to obtain GTR (p < 0.001) were predictors of future recurrence. On multivariate analysis a prior history of recurrence (p = 0.02) and an STR (p < 0.01) were independent predictors of a recurrence. Assessing only patients with primary presentations, STR and WHO Grades II and III were independent predictors of recurrence (p < 0.001 for both). CONCLUSIONS Patients with skull

  19. Intraparenchymal hemorrhage from dural metastasis of breast cancer mimicking meningioma.

    PubMed

    Seki, Syunsuke; Kamide, Tomoya; Tamase, Akira; Mori, Kentaro; Yanagimoto, Kunio; Nomura, Motohiro

    2016-06-01

    Intraparenchymal hemorrhage from dural metastasis of breast cancer is rare. A 54-year-old woman without a significant medical history showed altered consciousness and left hemiparesis. Radiological examination revealed an extra-axial mass in the right middle fossa with intraparenchymal hemorrhage and another mass invading the skull in the right parietal region. The pre-operative diagnosis was a sphenoid ridge meningioma presenting with intraparenchymal hemorrhage and another meningioma in the convexity. The tumors and hematoma were removed. Pathological findings of the tumors were compatible with adenocarcinoma. Systemic examination revealed breast cancer with metastasis to the spine. Although the radiological findings were similar to those of meningioma, a differential diagnosis of metastatic brain tumor with intraparenchymal hemorrhage should be taken into consideration. PMID:26975475

  20. Gene expression analysis of aberrant signaling pathways in meningiomas

    PubMed Central

    TORRES-MARTÍN, MIGUEL; MARTINEZ-GLEZ, VICTOR; PEÑA-GRANERO, CAROLINA; ISLA, ALBERTO; LASSALETTA, LUIS; DE CAMPOS, JOSE M.; PINTO, GIOVANNY R.; BURBANO, ROMMEL R.; MELÉNDEZ, BÁRBARA; CASTRESANA, JAVIER S.; REY, JUAN A.

    2013-01-01

    Examining aberrant pathway alterations is one method for understanding the abnormal signals that are involved in tumorigenesis and tumor progression. In the present study, expression arrays were performed on tumor-related genes in meningiomas. The GE Array Q Series HS-006 was used to determine the expression levels of 96 genes that corresponded to six primary biological regulatory pathways in a series of 42 meningiomas, including 32 grade I, four recurrent grade I and six grade II tumors, in addition to three normal tissue controls. Results showed that 25 genes that were primarily associated with apoptosis and angiogenesis functions were downregulated and 13 genes frequently involving DNA damage repair functions were upregulated. In addition to the inactivation of the neurofibromin gene, NF2, which is considered to be an early step in tumorigenesis, variations of other biological regulatory pathways may play a significant role in the development of meningioma. PMID:23946817

  1. Gene expression analysis of aberrant signaling pathways in meningiomas.

    PubMed

    Torres-Martín, Miguel; Martinez-Glez, Victor; Peña-Granero, Carolina; Isla, Alberto; Lassaletta, Luis; DE Campos, Jose M; Pinto, Giovanny R; Burbano, Rommel R; Meléndez, Bárbara; Castresana, Javier S; Rey, Juan A

    2013-07-01

    Examining aberrant pathway alterations is one method for understanding the abnormal signals that are involved in tumorigenesis and tumor progression. In the present study, expression arrays were performed on tumor-related genes in meningiomas. The GE Array Q Series HS-006 was used to determine the expression levels of 96 genes that corresponded to six primary biological regulatory pathways in a series of 42 meningiomas, including 32 grade I, four recurrent grade I and six grade II tumors, in addition to three normal tissue controls. Results showed that 25 genes that were primarily associated with apoptosis and angiogenesis functions were downregulated and 13 genes frequently involving DNA damage repair functions were upregulated. In addition to the inactivation of the neurofibromin gene, NF2, which is considered to be an early step in tumorigenesis, variations of other biological regulatory pathways may play a significant role in the development of meningioma. PMID:23946817

  2. Radiation-induced cerebral meningioma: a recognizable entity

    SciTech Connect

    Rubinstein, A.B.; Shalit, M.N.; Cohen, M.L.; Zandbank, U.; Reichenthal, E.

    1984-11-01

    The authors retrospectively analyzed the clinical and histopathological findings in 201 patients with intracranial meningiomas operated on in the period 1978 to 1982. Forty-three of the patients (21.4%) had at some previous time received radiation treatment to their scalp, the majority for tinea capitis. The findings in these 43 irradiated patients were compared with those in the 158 non-irradiated patients. Several distinctive clinical and histological features were identified in the irradiated group, which suggest that radiation-induced meningiomas can be defined as a separate nosological subgroup. The use of irradiation in large numbers of children with tinea capitis in the era prior to the availability of griseofulvin may be responsible for a significantly increased incidence of intracranial meningiomas.

  3. Risk factors for meningiomas in men in Los Angeles County

    SciTech Connect

    Preston-Martin, S.; Yu, M.C.; Henderson, B.E.; Roberts, C.

    1983-05-01

    A case-control study among men in Los Angeles County was conducted to investigate further the causes of intracranial meningiomas. Meningioma patients and a neighbor of each one were interviewed about past experiences that might be associated with tumor development. Analysis of information from the 105 matched pairs showed an association with meningioma occurrence for various factors relating to head trauma and head X-rays: 1) ever boxed as a sport (odds ratio (OR) . 2.0, P . 0.03), 2) had a serious head injury (OR . 1.9, P . 0.01), and 3) had X-ray treatment to the head before 20 years of age and/or had five or more full mouth dental X-ray series before 1945 (OR . 3.5, P . 0.02). Of the 105 subjects, 72 (69%) had a history of exposure to at least one of these factors.

  4. Endonasal Endoscopic Management of Parasellar and Cavernous Sinus Meningiomas.

    PubMed

    Lobo, Bjorn; Zhang, Xin; Barkhoudarian, Garni; Griffiths, Chester F; Kelly, Daniel F

    2015-07-01

    The management of cavernous sinus and invasive parasellar meningiomas often requires a multimodality treatment approach. Early attempts at complete or near-complete removal of parasellar meningiomas involving the cavernous sinus, Meckel cave, clivus, and sella using anterolateral or lateral skull base approaches were typically unsuccessful and yielded high rates of new cranial neuropathy and other complications. This article presents a strategy of endonasal endoscopic parasellar skull base bony decompression and limited tumor removal followed by stereotactic radiotherapy, stereotactic radiosurgery, or observation. Patient selection, technical nuances, potential complications, and initial outcomes in a small series of patients are discussed. PMID:26141358

  5. Expanded Endoscopic Endonasal Approaches to Skull Base Meningiomas

    PubMed Central

    Prosser, J. Drew; Vender, John R.; Alleyne, Cargill H.; Solares, C. Arturo

    2012-01-01

    Anterior cranial base meningiomas have traditionally been addressed via frontal or frontolateral approaches. However, with the advances in endoscopic endonasal treatment of pituitary lesions, the transphenoidal approach is being expanded to address lesions of the petrous ridge, anterior clinoid, clivus, sella, parasellar region, tuberculum, planum, olfactory groove, and crista galli regions. The expanded endoscopic endonasal approach (EEEA) has the advantage of limiting brain retraction and resultant brain edema, as well as minimizing manipulation of neural structures. Herein, we describe the techniques of transclival, transphenoidal, transplanum, and transcribiform resections of anterior skull base meningiomas. Selected cases are presented. PMID:23730542

  6. Recurrent prolactinoma and meningioma following irradiation and bromocriptine treatment

    SciTech Connect

    Kolodny, J.; Dluhy, R.G.

    1985-01-01

    This case report describes a 45-year-old man with a massive extrasellar prolactinoma, treated initially with surgery and radiotherapy, who experienced a dramatic reduction of the bulk of his tumor but persistence and subsequent progression of an extrasellar portion while receiving long-term bromocriptine therapy, despite stable, suppressed prolactin levels. Although the residual tumor was thought to be adenomatous tissue unresponsive to bromocriptine, a meningioma was ultimately diagnosed. Because the meningioma may have been radiation-induced, clinicians are reminded to consider a second neoplasm in cases of apparent bromocriptine treatment failures, especially when prolactin levels are stable.

  7. Rhabdoid papillary meningioma treated with 177Lu DOTATATE PRRT.

    PubMed

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-03-01

    An 18-year-old girl presented with a 3-year history of a recurrent skull base mass confirmed to be a rhabdoid papillary meningioma. The tumor was octreotide avid and metastatic to the lungs, thoracic lymph nodes, and bones, and she was referred for PRRT (peptide receptor radionuclide therapy) with 177Lu DOTATATE. After 3 induction treatment cycles of 177Lu DOTATATE, she experienced significant improvements in her symptoms; however, just before the fourth treatment, she developed cervical spinal cord compression and passed away shortly thereafter. The use of 177Lu DOTATATE therapy in the management of rhabdoid papillary meningioma warrants further research. PMID:25608146

  8. Cerebellar mature teratoma in adulthood.

    PubMed

    Zavanone, M; Alimehmeti, R; Campanella, R; Ram-Pini, P; Locatelli, M; Egidi, M; Righini, A; Bauer, D

    2002-03-01

    Mature teratoma of the posterior cranial fossa in adults is extremely rare. We report a particularly rare case of medio-lateral cerebellar mature teratoma that became symptomatic in a middle-aged man. The CT revealed the lesion of heterogeneous density with calcifications in the solid medial portion. Only the MRI could reliably define the borders of the cystic component extending into the left cerebellar lobe. Histologically the presence of fully matured representative tissues of the 3 germ layers ensured the diagnosis of mature teratoma. We suggest that the cyst formation from progressive latent hemorrhage and/or secretion from the gland cells of the tumor, may be responsible for the clinical decompensation even in adulthood. PMID:12118223

  9. Cerebellar neurocognition and Korsakoff's syndrome: an hypothesis.

    PubMed

    Wijnia, Jan W; Goossensen, Anne

    2010-08-01

    In literature, the cerebellum is given a substantial role in cognitive processes, in addition to traditional views on cerebellar function of regulating motor behaviour. The phenomenon of cerebellar damage causing impairments in memory and executive functioning was observed in various cerebellar disorders. Cerebellar cognitive dysfunction can be interpreted as a disturbance of cerebello-cerebral connections to areas of the cerebral cortex involved in cognitive processing, but the exact nature of the cognitive dysregulation is not known. Memory and executive dysfunction are important clinical features of Korsakoff's syndrome. We hypothesize that the Korsakoff syndrome might be an example of cerebellar neurocognitive dysfunctioning, caused by cerebello-cerebral pathways being disconnected in brain areas that are classically affected in Wernicke's encephalopathy. Further research is needed to support the possibility of cerebellar neurocognitive disturbances in Korsakoff's syndrome. If correct, this hypothesis may contribute to a better understanding of the clinical and neuropsychological profile of Korsakoff's syndrome. PMID:20303220

  10. Bevacizumab treatment for meningiomas in NF2: a retrospective analysis of 15 patients.

    PubMed

    Nunes, Fabio P; Merker, Vanessa L; Jennings, Dominique; Caruso, Paul A; di Tomaso, Emmanuelle; Muzikansky, Alona; Barker, Fred G; Stemmer-Rachamimov, Anat; Plotkin, Scott R

    2013-01-01

    Bevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined. To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas. PMID:23555840

  11. The role of MAPK signaling pathway in the Her-2-positive meningiomas.

    PubMed

    Wang, Zhaoyin; Wang, Weijia; Xu, Shan; Wang, Shanshan; Tu, Yi; Xiong, Yifeng; Mei, Jinhong; Wang, Chunliang

    2016-08-01

    Meningiomas are common types of adult nerve system tumors. Although most cases are considered benign, due to its high rate of recurrence and easy malignant progression to anaplastic meningioma they present a puzzle for the current treatment. The HER-2 oncogene has important value for meningioma cells development and progression. So far, little is known about the effect on the exact underlying signal pathway and molecular mechanisms of HER-2-positive meningioma cells. The goal of the present study was to determine the effects of HER-2 gene and possible involvement of MAPK signal pathway in human malignant meningioma. We applied q-PCR analysis, immunofluorescence (IF) staining, western blot analysis, animal model, MAPK inhibition, MTT assay and cell invasion analysis for the investigation. The results demonstrated that the downregulation of the expression of HER-2 significantly inhibited cell motility and proliferation of human meningioma cells in vivo. Accordingly, in the HER-2-overexpression meningioma cells with the inhibition of ERK1/2, ERK5, JNK, in the cells with the ERK1/2, ERK5 inhibition, protein expression was markedly suppressed as well as the cell proliferation resistance. No difference was observed in the HER-2-overexpression meningioma cells with the inhibition of JNK. These findings suggest that HER-2 gene can affect the proliferation ability of human meningioma cells in vivo and MAPK signal pathway may contribute to the carcinogenesis and development of human meningiomas combinating with HER-2. PMID:27279438

  12. The role of MAPK signaling pathway in the Her-2-positive meningiomas

    PubMed Central

    Wang, Zhaoyin; Wang, Weijia; Xu, Shan; Wang, Shanshan; Tu, Yi; Xiong, Yifeng; Mei, Jinhong; Wang, Chunliang

    2016-01-01

    Meningiomas are common types of adult nerve system tumors. Although most cases are considered benign, due to its high rate of recurrence and easy malignant progression to anaplastic meningioma they present a puzzle for the current treatment. The HER-2 oncogene has important value for meningioma cells development and progression. So far, little is known about the effect on the exact underlying signal pathway and molecular mechanisms of HER-2-positive meningioma cells. The goal of the present study was to determine the effects of HER-2 gene and possible involvement of MAPK signal pathway in human malignant meningioma. We applied q-PCR analysis, immunofluorescence (IF) staining, western blot analysis, animal model, MAPK inhibition, MTT assay and cell invasion analysis for the investigation. The results demonstrated that the downregulation of the expression of HER-2 significantly inhibited cell motility and proliferation of human meningioma cells in vivo. Accordingly, in the HER-2-overexpression meningioma cells with the inhibition of ERK1/2, ERK5, JNK, in the cells with the ERK1/2, ERK5 inhibition, protein expression was markedly suppressed as well as the cell proliferation resistance. No difference was observed in the HER-2-overexpression meningioma cells with the inhibition of JNK. These findings suggest that HER-2 gene can affect the proliferation ability of human meningioma cells in vivo and MAPK signal pathway may contribute to the carcinogenesis and development of human meningiomas combinating with HER-2. PMID:27279438

  13. Posttranscriptional deregulation of signaling pathways in meningioma subtypes by differential expression of miRNAs

    PubMed Central

    Ludwig, Nicole; Kim, Yoo-Jin; Mueller, Sabine C.; Backes, Christina; Werner, Tamara V.; Galata, Valentina; Sartorius, Elke; Bohle, Rainer M.; Keller, Andreas; Meese, Eckart

    2015-01-01

    Background Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the affected signaling pathways. Methods In this study, we compared expression of 1205 miRNAs in different meningioma grades and histological subtypes using microarrays and independently validated deregulation of selected miRNAs with quantitative real-time PCR. Clinical utility of a subset of miRNAs as biomarkers for World Health Organization (WHO) grade II meningioma based on quantitative real-time data was tested. Potential targets of deregulated miRNAs were discovered with an in silico analysis. Results We identified 13 miRNAs deregulated between different subtypes of benign meningiomas, and 52 miRNAs deregulated in anaplastic meningioma compared with benign meningiomas. Known and putative target genes of deregulated miRNAs include genes involved in epithelial-to-mesenchymal transition for benign meningiomas, and Wnt, transforming growth factor–β, and vascular endothelial growth factor signaling for higher-grade meningiomas. Furthermore, a 4-miRNA signature (miR-222, -34a*, -136, and -497) shows promise as a biomarker differentiating WHO grade II from grade I meningiomas with an area under the curve of 0.75. Conclusions Our data provide novel insights into the contribution of miRNAs to the phenotypic spectrum in benign meningiomas. By deregulating translation of genes belonging to signaling pathways known to be important for meningioma genesis and progression, miRNAs provide a second in line amplification of growth promoting cellular signals. MiRNAs as biomarkers for diagnosis of aggressive meningiomas might prove useful and should be explored further in a prospective manner. PMID:25681310

  14. MicroRNA-18a regulates invasive meningiomas via hypoxia-inducible factor-1α

    PubMed Central

    LI, PUXIAN; GAO, YONG; LI, FENGJIA; PAN, QIANG; LIU, ZHENRUI; LU, XIANGDONG; SONG, CHUNYU; DIAO, XINGTAO

    2015-01-01

    The aim of the present study was to investigate the effects of microRNA-18a (miR-18a) on the invasiveness and metastasis of invasive meningiomas and the underlying mechanism. A total of 69 patients with meningiomas (30 patients in the invasive meningioma group and 39 patients in the non-invasive meningioma group) and 48 cases in the control group were enrolled. Samples of meningioma tissues, serum and cerebrospinal fluid were collected. Reverse transcription-quantitative polymerase chain reaction was performed to quantify the expression levels of hypoxia-inducible factor-1α (HIF-1α) mRNA and miR-18a. Western blot analysis was used to determine protein expression levels of HIF-1α. The expression levels of HIF-1α mRNA and protein in all three types of sample from the invasive meningioma group were significantly higher compared with those in the control and non-invasive meningioma groups (P<0.05), and the expression levels of HIF-1α mRNA in the serum and cerebrospinal fluid of the non-invasive meningioma group were significantly higher compared with those in the control group (P<0.05). The expression levels of miR-18a in the invasive meningioma group were significantly reduced compared with those in the control and non-invasive meningioma groups (P<0.05), whereas the levels of miR-18a in the non-invasive meningioma group were significantly lower compared with those in the control group (P<0.05). The expression of HIF-1α is significantly upregulated in patients with invasive meningiomas, possibly due to the downregulation of miR-18a expression. Therefore, miR-18a may regulate invasive meningiomas via HIF-1α. PMID:26622458

  15. Diagnosis of meningioma by time-resolved fluorescence spectroscopy.

    PubMed

    Butte, Pramod V; Pikul, Brian K; Hever, Aviv; Yong, William H; Black, Keith L; Marcu, Laura

    2005-01-01

    We investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for the intraoperative rapid evaluation of tumor specimens and delineation of tumor from surrounding normal tissue. Tissue autofluorescence is induced with a pulsed nitrogen laser (337 nm, 1.2 ns) and the intensity decay profiles are recorded in the 370 to 500 nm spectral range with a fast digitizer (0.2 ns resolution). Experiments are conducted on excised specimens (meningioma, dura mater, cerebral cortex) from 26 patients (97 sites). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site are used for tissue characterization. A linear discriminant analysis algorithm is used for tissue classification. Our results reveal that meningioma is characterized by unique fluorescence characteristics that enable discrimination of tumor from normal tissue with high sensitivity (>89%) and specificity (100%). The accuracy of classification is found to increase (92.8% cases in the training set and 91.8% in the cross-validated set correctly classified) when parameters from both the spectral and the time domain are used for discrimination. Our findings establish the feasibility of using TR-LIFS as a tool for the identification of meningiomas and enables further development of real-time diagnostic tools for analyzing surgical tissue specimens of meningioma or other brain tumors. PMID:16409091

  16. Rare Parenchyma Meningioma in an Adolescent Female With Cheek Tingling

    PubMed Central

    Liang, Wenjie; Li, Meirong

    2016-01-01

    Abstract The following is a report on a rare parenchyma meningioma and the computed tomography (CT) and magnetic resonance imaging (MRI) findings. To our knowledge, this was the first characterization of magnetic resonance spectroscopy (MRS) in a parenchyma meningioma. Three days after initial presentation, a 14-year-old female student reported feeling tingling in her cheek, grading 3 to 4 points. Two hours later, the tingling had disappeared. The patient was admitted to hospital with stable vital signs and no abnormal presentations upon physical examination. A routine CT scan of the brain showed a quasicircular region of the left occipital lobe was homogenous hyperdense and an arcualia calcification was found on the lesion's margin and the boundary was ill-defined. Further MRI and contrast-enhanced scanning of the brain showed that a lobulated nidus with abnormal signaling was present in the left occipital lobe and was approximately 1.9 × 2.0 cm. Hypointensity on T1-weighted imaging and a slight hyperintensity on T2-weighted imaging was also observed. A short T2 signal appeared on the margin and a few longer T2 edema zones appeared around the nidus, whereas the lesion showed homogenous enhancement. MRS was characterized by a slight or moderate increase of a choline (Cho) peak and a small reduction of the N-acetyl aspartate (NAA) peak. After completing the preoperative preparation, the excision of the supratentorial deep lesions was performed on the patient. The pathology led to a diagnosis of a left occipital lobe meningioma, WHO I. The patient was followed-up for 14 months postoperation, and had no reoccurrences. Intraparenchymal meningioma rarely occurs in brain parenchyma, and is characterized by lesions with abundant blood supply and requires a glioma to be identified. MRS is a potential tool for preoperative diagnosis of intraparenchymal meningioma. PMID:27082619

  17. Radiation Therapy Alone for Imaging-Defined Meningiomas

    SciTech Connect

    Korah, Mariam P.; Nowlan, Adam W.; Johnstone, Peter A.S.; Crocker, Ian R.

    2010-01-15

    Purpose: To assess local control and treatment-related toxicity of single-modality radiation therapy (RT) in the treatment of imaging-defined meningiomas. Methods and Materials: The records of Emory University School of Medicine, Atlanta, GA, were reviewed between 1985 and 2003. We identified 41 patients with 42 meningiomas treated with RT alone for lesions diagnosed on imaging alone. No patients received a histologic diagnosis. Patients in whom there was uniform agreement that the tumor represented a meningioma were accepted for therapy. Of the patients, 22 were treated with stereotactic radiosurgery (SRS), 11 with fractionated stereotactic radiotherapy (FSR), and 9 with three-dimensional conformal therapy (3DCRT). The median doses of SRS, FSR, and 3DCRT were 14 Gy, 50.4 Gy, and 52.2 Gy, respectively. Results: Median follow-up was 60 months. Of 42 meningiomas, 39 were locally controlled. The 8-year actuarial local control rate by Kaplan-Meier methods was 94%. One failure occurred 6 months after 3DCRT, a second at 34 months after FSR, and a third at 125 months after SRS. A temporary symptomatic radiation-related neurologic sequela developed in 1 patient treated with SRS. No fatal treatment complications occurred. The 8-year rate for actuarial freedom from complication survival by Kaplan-Meier methods was 97%. Conclusions: RT alone is an attractive alternative to surgery for imaging-defined meningiomas without significant mass effect. It offers local control comparable to surgical resection with minimal morbidity. RT should be considered as a viable alternative to surgery for tumors in various locations.

  18. Assessment of candidate immunohistochemical prognostic markers of meningioma recurrence.

    PubMed

    Csonka, T; Murnyák, B; Szepesi, R; Bencze, J; Bognár, L; Klekner, A; Hortobágyi, T

    2016-01-01

    Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely

  19. Learning of Sensory Sequences in Cerebellar Patients

    ERIC Educational Resources Information Center

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

  20. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  1. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  2. Cerebellar Stroke-manifesting as Mania.

    PubMed

    Jagadesan, Venkatesan; Thiruvengadam, Kannapiran R; Muralidharan, Rengarajalu

    2014-07-01

    Secondary mania resulting from cerebral Cortex are described commonly. But secondary mania produced by cerebellar lesions are relatively uncommon. This case report describes a patient who developed cerebellar stoke and manic features simultaneously. 28 years old male developed giddiness and projectile vomiting. Then he would lie down for about an hour only to find that he could not walk. He became quarrelsome. His Psycho motor activities and speech were increased. He was euphoric and was expressing grandiose ideas. Bender Gestalt Test showed signs of organicity. Score in Young mania relating scale was 32; productivity was low in Rorschach. Neurological examination revealed left cerebellar signs like ataxia and slurring of speech. Computed tomography of brain showed left cerebellar infarct. Relationship between Psychiatric manifestations and cerebellar lesion are discussed. PMID:25035567

  3. Cerebellar Stroke-manifesting as Mania

    PubMed Central

    Jagadesan, Venkatesan; Thiruvengadam, Kannapiran R.; Muralidharan, Rengarajalu

    2014-01-01

    Secondary mania resulting from cerebral Cortex are described commonly. But secondary mania produced by cerebellar lesions are relatively uncommon. This case report describes a patient who developed cerebellar stoke and manic features simultaneously. 28 years old male developed giddiness and projectile vomiting. Then he would lie down for about an hour only to find that he could not walk. He became quarrelsome. His Psycho motor activities and speech were increased. He was euphoric and was expressing grandiose ideas. Bender Gestalt Test showed signs of organicity. Score in Young mania relating scale was 32; productivity was low in Rorschach. Neurological examination revealed left cerebellar signs like ataxia and slurring of speech. Computed tomography of brain showed left cerebellar infarct. Relationship between Psychiatric manifestations and cerebellar lesion are discussed. PMID:25035567

  4. Cellular and molecular basis of cerebellar development

    PubMed Central

    Martinez, Salvador; Andreu, Abraham; Mecklenburg, Nora; Echevarria, Diego

    2013-01-01

    Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering, and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification, and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function. PMID:23805080

  5. Asymptomatic cerebellar atrophy after acute enteroviral encephalitis.

    PubMed

    Vitaszil, Edina; Kamondi, Anita; Csillik, Anita; Velkey, Imre; Szirmai, Imre

    2005-07-01

    We report on a 13-year-old male who had acute enteroviral encephalitis causing cerebellar symptoms at the age of 10 years. Magnetic resonance imaging (MRI) showed no abnormalities. Clinically he appeared to be recovered completely after 6 months. Twenty-three months after the recovery, MRI was performed because he presented with slight lower-limb and truncal ataxia experienced as lack of foot coordination while playing football or riding a bicycle. MRI demonstrated severe cerebellar atrophy. Clinically he recovered completely in 10 days. Only sophisticated electrophysiological methods revealed cerebellar dysfunction. The case provides evidence for the plasticity of cerebellar regulatory structures involved in the coordination of fine movements. It seems that in childhood the slow, isolated disintegration of cerebellar systems can be compensated for by upper thalamic or telencephalic connections, in a similar way to a congenital deficit of the cerebellum. PMID:15991870

  6. Improvement in Visual Fields After Treatment of Intracranial Meningioma With Bevacizumab.

    PubMed

    Ly, K Ina; Hamilton, Steven R; Rostomily, Robert C; Rockhill, Jason K; Mrugala, Maciej M

    2015-12-01

    High-grade (World Health Organization [WHO] Grade II and III) meningiomas constitute a minority of all meningioma cases but are associated with significant morbidity and mortality, due to more aggressive tumor behavior and a tendency to recur despite standard therapy with resection and radiotherapy. They display a higher degree of vascularity than WHO Grade I meningiomas and produce angiogenic and growth factors, including vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF-A, has been used in the treatment of recurrent or progressive meningiomas resistant to standard therapy. We report a patient with a recurrent left frontotemporal meningioma and associated-vision loss who experienced substantial visual field recovery after 3 cycles of bevacizumab. In addition, we provide a review of the literature regarding the efficacy of bevacizumab in the treatment of recurrent meningiomas. PMID:26049681

  7. Genetic Profiling by Single-Nucleotide Polymorphism-Based Array Analysis Defines Three Distinct Subtypes of Orbital Meningioma

    PubMed Central

    Ho, Cheng-Ying; Mosier, Stacy; Safneck, Janice; Salomao, Diva R.; Miller, Neil R.; Eberhart, Charles G.; Gocke, Christopher D.; Batista, Denise A. S.; Rodriguez, Fausto J.

    2015-01-01

    Orbital meningiomas can be classified as primary optic nerve sheath (ON) meningiomas, primary intraorbital ectopic (Ob) meningiomas and spheno-orbital (Sph-Ob) meningiomas based on anatomic site. Single-nucleotide polymorphism (SNP)-based array analysis with the Illumina 300K platform was performed on formalin-fixed, paraffin-embedded tissue from 19 orbital meningiomas (5 ON, 4 Ob and 10 Sph-Ob meningiomas). Tumors were World Health Organization (WHO) grade I except for two grade II meningiomas, and one was NF2-associated. We found genomic alterations in 68% (13 of 19) of orbital meningiomas. Sph-Ob tumors frequently exhibited monosomy 22/22q loss (70%; 7/10) and deletion of chromosome 1p, 6q and 19p (50% each; 5/10). Among genetic alterations, loss of chromosome 1p and 6q were more frequent in clinically progressive tumors. Chromosome 22q loss also was detected in the majority of Ob meningiomas (75%; 3/4) but was infrequent in ON meningiomas (20%; 1/5). In general, Ob tumors had fewer chromosome alterations than Sph-Ob and ON tumors. Unlike Sph-Ob meningiomas, most of the Ob and ON meningiomas did not progress even after incomplete excision, although follow-up was limited in some cases. Our study suggests that ON, Ob and Sph-Ob meningiomas are three molecularly distinct entities. Our results also suggest that molecular subclassification may have prognostic implications. PMID:24773246

  8. Developmental Cerebellar Cognitive Affective Syndrome in Ex-preterm Survivors Following Cerebellar Injury

    PubMed Central

    Brossard-Racine, Marie; du Plessis, Adre J.; Limperopoulos, Catherine

    2015-01-01

    Cerebellar injury is increasingly recognized as an important complication of very preterm birth. However, the neurodevelopmental consequences of early life cerebellar injury in prematurely born infants have not been well elucidated. We performed a literature search of studies published between 1997 and 2014 describing neurodevelopmental outcomes of preterm infants following direct cerebellar injury or indirect cerebellar injury/underdevelopment. Available data suggests that both direct and indirect mechanisms of cerebellar injury appear to stunt cerebellar growth and adversely affect neurodevelopment. This review also provides important insights into the highly integrated cerebral-cerebellar structural and functional correlates. Finally, this review highlights that early life impairment of cerebellar growth extends far beyond motor impairments and plays a critical, previously underrecognized role in the long-term cognitive, behavioral, and social deficits associated with brain injury among premature infants. These data point to a developmental form of the cerebellar cognitive affective syndrome previously described in adults. Longitudinal prospective studies using serial advanced magnetic resonance imaging techniques are needed to better delineate the full extent of the role of prematurity-related cerebellar injury and topography in the genesis of cognitive, social-behavioral dysfunction. PMID:25241880

  9. EGFR soluble isoforms and their transcripts are expressed in meningiomas.

    PubMed

    Guillaudeau, Angélique; Durand, Karine; Bessette, Barbara; Chaunavel, Alain; Pommepuy, Isabelle; Projetti, Fabrice; Robert, Sandrine; Caire, François; Rabinovitch-Chable, Hélène; Labrousse, François

    2012-01-01

    The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%. Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types. PMID:22623992

  10. Cerebellar Motor Function in Spina Bifida Meningomyelocele

    PubMed Central

    Dennis, Maureen; Salman, Michael S.; Juranek, Jenifer; Fletcher, Jack M.

    2010-01-01

    Spina bifida meningomyelocele (SBM), a congenital neurodevelopmental disorder, involves dysmorphology of the cerebellum, and its most obvious manifestations are motor deficits. This paper reviews cerebellar neuropathology and motor function across several motor systems well studied in SBM in relation to current models of cerebellar motor and timing function. Children and adults with SBM have widespread motor deficits in trunk, upper limbs, eyes, and speech articulators that are broadly congruent with those observed in adults with cerebellar lesions. The structure and function of the cerebellum are correlated with a range of motor functions. While motor learning is generally preserved in SBM, those motor functions requiring predictive signals and precise calibration of the temporal features of movement are impaired, resulting in deficits in smooth movement coordination as well as in the classical cerebellar triad of dysmetria, ataxia, and dysarthria. That motor function in individuals with SBM is disordered in a manner phenotypically similar to that in adult cerebellar lesions, and appears to involve similar deficits in predictive cerebellar motor control, suggests that age-based cerebellar motor plasticity is limited in individuals with this neurodevelopmental disorder. PMID:20652468

  11. X-linked disorders with cerebellar dysgenesis

    PubMed Central

    2011-01-01

    X-linked disorders with cerebellar dysgenesis (XLCD) are a genetically heterogeneous and clinically variable group of disorders in which the hallmark is a cerebellar defect (hypoplasia, atrophy or dysplasia) visible on brain imaging, caused by gene mutations or genomic imbalances on the X-chromosome. The neurological features of XLCD include hypotonia, developmental delay, intellectual disability, ataxia and/or other cerebellar signs. Normal cognitive development has also been reported. Cerebellar dysgenesis may be isolated or associated with other brain malformations or multiorgan involvement. There are at least 15 genes on the X-chromosome that have been constantly or occasionally associated with a pathological cerebellar phenotype. 8 XLCD loci have been mapped and several families with X-linked inheritance have been reported. Recently, two recurrent duplication syndromes in Xq28 have been associated with cerebellar hypoplasia. Given the report of several forms of XLCD and the excess of males with ataxia, this group of conditions is probably underestimated and families of patients with neuroradiological and clinical evidence of a cerebellar disorder should be counseled for high risk of X-linked inheritance. PMID:21569638

  12. Differentiation of Benign Angiomatous and Microcystic Meningiomas with Extensive Peritumoral Edema from High Grade Meningiomas with Aid of Diffusion Weighted MRI

    PubMed Central

    Azizyan, Avetis; Eboli, Paula; Drazin, Doniel; Mirocha, James; Maya, Marcel M.; Bannykh, Serguei

    2014-01-01

    Objective. To determine whether angiomatous and microcystic meningiomas which mimic high grade meningiomas based on extent of peritumoral edema can be reliably differentiated as low grade tumors using normalized apparent diffusion coefficient (ADC) values. Methods. Preoperative magnetic resonance imaging (MRI) of seventy patients with meningiomas was reviewed. Morphologically, the tumors were divided into 3 groups. Group 1 contained 12 pure microcystic, 3 pure angiomatoid and 7 mixed angiomatoid and microcystic tumors. Group 2 included World Health Organization (WHO) grade II and WHO grade III tumors, of which 28 were atypical and 9 were anaplastic meningiomas. Group 3 included WHO grade I tumors of morphology different than angiomatoid and microcystic. Peritumoral edema, normalized ADC, and cerebral blood volume (CBV) were obtained for all meningiomas. Results. Edema index of tumors in group 1 and group 2 was significantly higher than in group 3. Normalized ADC value in group 1 was higher than in group 2, but not statistically significant between groups 1 and 3. CBV values showed no significant group differences. Conclusion. A combination of peritumoral edema index and normalized ADC value is a novel approach to preoperative differentiation between true aggressive meningiomas and mimickers such as angiomatous and microcystic meningiomas. PMID:25478572

  13. Pediatric Neurocutaneous Syndromes with Cerebellar Involvement.

    PubMed

    Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

    2016-08-01

    Neurocutaneous syndromes encompasses a broad group of genetic disorders with different clinical, genetic, and pathologic features that share developmental lesions of the skin as well as central and peripheral nervous system. Cerebellar involvement has been shown in numerous types of neurocutaneous syndrome. It may help or be needed for the diagnosis and to explain the cognitive and behavioral phenotype of affected children. This article describes various types of neurocutaneous syndrome with cerebellar involvement. For each neurocutaneous disease or syndrome, clinical features, genetic, neuroimaging findings, and the potential role of the cerebellar involvement is discussed. PMID:27423801

  14. Sonic hedgehog patterning during cerebellar development.

    PubMed

    De Luca, Annarita; Cerrato, Valentina; Fucà, Elisa; Parmigiani, Elena; Buffo, Annalisa; Leto, Ketty

    2016-01-01

    The morphogenic factor sonic hedgehog (Shh) actively orchestrates many aspects of cerebellar development and maturation. During embryogenesis, Shh signaling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Shh secreted by Purkinje cells sustains the amplification of postnatal neurogenic niches: the external granular layer and the prospective white matter, where excitatory granule cells and inhibitory interneurons are produced, respectively. Moreover, Shh signaling affects Bergmann glial differentiation and promotes cerebellar foliation during development. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying its role in physiological and pathological conditions. PMID:26499980

  15. Primary intra-fourth ventricular meningioma: Report two cases

    PubMed Central

    Sadashiva, Nishanth; Rao, Shilpa; Srinivas, Dwarakanath; Shukla, Dhaval

    2016-01-01

    Meningioma's occurring intraventricular region are rare and these occurring in the fourth ventricle is even rare. Because of the rarity, it is not usually considered as a differential diagnosis in any age group. Clinical features and Imaging is not characteristic, and most of them are thought to be some different tumor. Here, we discuss two cases harboring a primary fourth ventricular meningioma Grade II, which was surgically excised successfully. Total excision was achieved in both cases and as the tumor was firm to soft and vermian splitting was not required. Understanding the clinical features and a careful preoperative radiological examination is required to differentiate this tumor from more commonly occurring lesions at this location. PMID:27114661

  16. Parameters influencing local control of meningiomas treated with radiosurgery.

    PubMed

    Kaprealian, Tania; Raleigh, David R; Sneed, Penny K; Nabavizadeh, Nima; Nakamura, Jean L; McDermott, Michael W

    2016-06-01

    To identify parameters that influence local control after stereotactic radiosurgery (SRS) for meningiomas we retrospectively analyzed all meningiomas treated with Gamma Knife SRS at our institution from 1991 to 2007. Endpoints were measured from the date of SRS and estimated using the Kaplan-Meier method; subgroups were compared with log-rank tests. Sex, performance status, age, SRS setting, radiation dose, grade, volume and location were evaluated with univariate and multivariate Cox proportional hazards analyses. Of 280 patients with 438 tumors, 264 patients with clinical follow-up and 406 tumors with imaging follow-up were analyzed (median follow-up: 75.9 months). Thirty-seven percent of the tumors had no tissue diagnosis, 32 % were benign (grade I), 12 % atypical (grade II), and 19 % malignant (grade III). Five-year freedom from progression (FFP) was 97 % for presumed meningiomas, 87 % for grade I tumors, 56 % for grade II tumors, and 47 % for grade III tumors (p < 0.0001). Five-year FFP probabilities for upfront SRS versus SRS at recurrence after surgery versus SRS at recurrence after RT were 97, 86, and 38 %, respectively (p < 0.0001). Univariate analysis revealed that higher grade, larger target volume (median diameter: 2.4 cm) and SRS setting were associated with poorer FFP. Only target volume and SRS setting remained significant on multivariate analysis. Local control of presumed and grade I meningiomas is excellent with Gamma Knife SRS, but is suboptimal with high-grade tumors as well as for those treated at recurrence after RT or of large volume. PMID:27131883

  17. Presentation and Patterns of Late Recurrence of Olfactory Groove Meningiomas

    PubMed Central

    Snyder, William E.; Shah, Mitesh V.; Weisberger, Edward C.; Campbell, Robert L.

    2000-01-01

    The objective of this article is to present the recurrence pattern of olfactory groove meningiomas after surgical resection. Four patients, one female and three males, with surgically resected olfactory groove meningiomas presented with tumor recurrence. All patients underwent resection of an olfactory groove meningioma and later presented with recurrent tumors. The mean age at initial diagnosis was 47 years. All presented initially with vision changes, anosmia, memory dysfunction, and personality changes. Three patients had a preoperative MRI scan. All patients had a craniotomy, with gross total resection achieved in three, and 90% tumor removal achieved in the fourth. Involved dura was coagulated, but not resected, in all cases. Three patients were followed with routine head CT scans postoperatively, and none was followed with MRI scan. The mean time to recurrence was 6 years. Three patients presented with recurrent visual deterioration, and one presented with symptoms of nasal obstruction. Postoperative CT scans failed to document early tumor recurrence, whereas MRI documented tumor recurrence in all patients. Tumor resection and optic nerve decompression improved vision in two patients and stabilized vision in two. Complete resection was not possible because of extensive bony involvement around the anterior clinoid and inferior to the anterior cranial fossa in all cases. Evaluation of four patients with recurrent growth of olfactory groove meningiomas showed the epicenter of recurrence to be inferior to the anterior cranial fossa, with posterior extension involving the optic canals, leading to visual deterioration. This location led to a delay in diagnosis in patients who were followed only with routine CT scans. Initial surgical procedures should include removal of involved dura and bone, and follow-up evaluation should include formal ophthalmologic evaluations and routine head MRI scans. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID

  18. Tumor infiltrating immune cells in gliomas and meningiomas.

    PubMed

    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Miranda, David; Ruiz, Laura; Sousa, Pablo; Ciudad, Juana; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2016-03-01

    Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control. PMID:26216710

  19. Female predominance in meningiomas can not be explained by differences in progesterone, estrogen, or androgen receptor expression.

    PubMed

    Korhonen, Katariina; Salminen, Tiina; Raitanen, Jani; Auvinen, Anssi; Isola, Jorma; Haapasalo, Hannu

    2006-10-01

    The female predominance in meningioma incidence and association between meningioma and breast cancer suggest that growth of meningiomas is hormone-dependent. There are several discrepancies in literature about the proliferative effect of sex hormones on meningiomas. This study aims to evaluate the hormone receptor status of meningiomas and assess its relation to age, sex, histological grade, recurrence, and proliferation activity. The material was based on consecutive patients operated for meningioma at Tampere University Hospital in 1989-1999. The occurrence of progesterone, estrogen and androgen receptor in patients with primary and recurrent meningiomas was studied immunohistochemically by using specific monoclonal antibodies. Hormonal status was determined in 510 tumor samples. 443 samples were from primary meningiomas and 67 from recurrent tumors. Of the samples, 455 were benign (WHO grade I), 49 atypical (grade II), and 6 malignant (grade III). Of the primary tumor samples, 88% were progesterone receptor positive, 40% were positive for estrogen and 39% for androgen receptors. Grade I meningiomas had significantly higher incidence for estrogen and androgen receptors than higher grade meningiomas. Estrogen positive tumor samples had significantly higher proliferation index than estrogen negative samples. No difference in expression of sex hormone receptors was observed by sexes or age group. Estrogen and androgen receptors may have more influence on the pathogenesis of meningiomas than earlier thought. The higher incidence of meningiomas in women can not be explained by differences of sex hormone receptor expression. PMID:16703453

  20. Stereotactic fractionated radiotherapy for the treatment of benign meningiomas

    SciTech Connect

    Candish, Charles; McKenzie, Michael . E-mail: mmckenzi@bccancer.bc.edu; Clark, Brenda G.; Ma, Roy; Lee, Richard; Vollans, Emily; Robar, James; Gete, Ermias; Martin, Monty

    2006-11-15

    Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm{sup 3} and 18.9 cm{sup 3}, respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-made blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45-50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective.

  1. Cognitive functioning in meningioma patients: a systematic review.

    PubMed

    Meskal, Ikram; Gehring, Karin; Rutten, Geert-Jan M; Sitskoorn, Margriet M

    2016-06-01

    This systematic review evaluates relevant findings and methodologic aspects of studies on cognitive functioning in meningioma patients prior to and/or following surgery with or without adjuvant radiotherapy. PubMed and Web of Science electronic databases were searched until December 2015. From 1012 initially identified articles, 11 met the inclusion criteria for this review. Multiple methodological limitations were identified which include the lack of pre-treatment assessments, variations in the number and types of neuropsychological tests used, the normative data used to identify patients with cognitive deficits, and the variety of definitions for cognitive impairment. Study results suggest that most of meningioma patients are faced with cognitive deficits in several cognitive domains prior to surgery. Following surgery, most of these patients seem to improve in cognitive functioning. However, they still have impairments in a wide range of cognitive functions compared to healthy controls. Suggestions are given for future research. Adequate diagnosis and treatment of cognitive deficits may ultimately lead to improved outcome and quality of life in meningioma patients. PMID:27048208

  2. Expressions of Endocan in Patients with Meningiomas and Gliomas

    PubMed Central

    Turk, Okan; Turkmen Inanir, Nursel

    2016-01-01

    Objective. Endocan has been shown to be a marker for several cancers and may show degree of malignancy. The aim of this study is to assess tissue levels of endocan in common brain tumors, namely, meningiomas, low-grade gliomas (LGGs), and high-grade gliomas (HGGs). Patients and Methods. Endocan was assayed by commercially available enzyme linked immunosorbent assay (ELISA) kits in a total of 50 brain tumors (20 meningiomas, 19 LGGs, and 20 HGGs) and 15 controls. The results were compared to control brain tissues. Results. Each tumor group showed significant higher levels of endocan compared to controls (p < 0.05). In addition, endocan levels showed steady increase from the least (meningiomas) to the most (HGGs) malignant tumors and positive correlation was noted between the degree of malignancy and endocan level (p = 0.0001). Conclusion. Endocan, a vital molecule for angiogenesis, is expressed in common brain tumors and results suggest that endocan could be a marker for malignancy. PMID:27528791

  3. Craniotomy for anterior cranial fossa meningiomas: historical overview.

    PubMed

    Morales-Valero, Saul F; Van Gompel, Jamie J; Loumiotis, Ioannis; Lanzino, Giuseppe

    2014-04-01

    The surgical treatment of meningiomas located at the base of the anterior cranial fossa is often challenging, and the evolution of the surgical strategy to resect these tumors parallels the development of craniotomy, and neurosurgery in general, over the past century. Early successful operations to treat these tumors were pioneered by prominent figures such as Sir William Macewen and Francesco Durante. Following these early reports, Harvey Cushing made significant contributions, allowing a better understanding and treatment of meningiomas in general, but particularly those involving the anterior cranial base. Initially, large-sized unilateral or bilateral craniotomies were necessary to approach these deep-seated lesions. Technical advances such as the introduction of electrosurgery, the operating microscope, and refined microsurgical instruments allowed neurosurgeons to perform less invasive surgical procedures with better results. Today, a wide variety of surgical strategies, including endoscopic surgery and radiosurgery, are used to treat these tumors. In this review, the authors trace the evolution of craniotomy for anterior cranial fossa meningiomas. PMID:24684326

  4. Fractionated Proton Radiotherapy for Benign Cavernous Sinus Meningiomas

    SciTech Connect

    Slater, Jerry D.; Loredo, Lilia N.; Chung, Arthur; Bush, David A.; Patyal, Baldev; Johnson, Walter D.; Hsu, Frank P.K.; Slater, James M.

    2012-08-01

    Purpose: To evaluate the efficacy of fractionated proton radiotherapy for a population of patients with benign cavernous sinus meningiomas. Methods and Materials: Between 1991 and 2002, 72 patients were treated at Loma Linda University Medical Center with proton therapy for cavernous sinus meningiomas. Fifty-one patients had biopsy or subtotal resection; 47 had World Health Organization grade 1 pathology. Twenty-one patients had no histologic verification. Twenty-two patients received primary proton therapy; 30 had 1 previous surgery; 20 had more than 1 surgery. The mean gross tumor volume was 27.6 cm{sup 3}; mean clinical target volume was 52.9 cm{sup 3}. Median total doses for patients with and without histologic verification were 59 and 57 Gy, respectively. Mean and median follow-up periods were 74 months. Results: The overall 5-year actuarial control rate was 96%; the control rate was 99% in patients with grade 1 or absent histologic findings and 50% for those with atypical histology. All 21 patients who did not have histologic verification and 46 of 47 patients with histologic confirmation of grade 1 tumor demonstrated disease control at 5 years. Control rates for patients without previous surgery, 1 surgery, and 2 or more surgeries were 95%, 96%, and 95%, respectively. Conclusions: Fractionated proton radiotherapy for grade 1 cavernous sinus meningiomas achieves excellent control rates with minimal toxicities, regardless of surgical intervention or use of histologic diagnosis. Disease control for large lesions can be achieved by primary fractionated proton therapy.

  5. Association of tamoxifen with meningioma: a population-based study in Sweden

    PubMed Central

    Sundquist, Jan; Sundquist, Kristina

    2016-01-01

    Previous studies suggest that hormone therapy may play an important role in the development of meningioma. However, it is unclear whether medication with tamoxifen can prevent meningioma. Our study cohort included all women who were diagnosed with breast cancer between 1961 and 2010, and a total of 227 535 women were identified with breast cancer with a median age at diagnosis of 63 years. Women diagnosed with breast cancer after 1987 were defined as tamoxifen exposed; those diagnosed with breast cancer before or during 1987 were defined as not exposed to tamoxifen. Standardized incidence ratios (SIRs) were used to calculate the risk of subsequent meningioma. Of these women, 223 developed meningioma. For women without tamoxifen exposure, the risk of meningioma was significantly increased, with an SIR of 1.54 (95% confidence interval 1.30–1.81); the risk was not increased in those with tamoxifen exposure (SIR=1.06, 95% confidence interval 0.84–1.32). The increased risk of meningioma in women without tamoxifen exposure persisted during 10 years of follow-up. In this historical cohort study, we found that women diagnosed with breast cancer but not treated with tamoxifen had an increased incidence of meningioma, whereas the incidence was close to that of the general population in patients treated with tamoxifen. This suggests that tamoxifen may prevent the development of meningioma. PMID:25642792

  6. Intraparenchymal meningioma within the basal ganglia of a child: A case report.

    PubMed

    Reynolds, Matthew R; Boland, Michael R; Arias, Eric J; Farrell, Michael; Javadpour, Mohsen; Caird, John

    2016-06-01

    Intraparenchymal meningiomas are rare. To date, no such lesion has been reported within the basal ganglia of a paediatric patient. Here, we describe the case of a 15-year-old-boy who presented with symptoms referable to a cystic, calcified, left basal ganglia intraparenchymal meningioma and discuss the surgical management of this lesion. PMID:26466020

  7. A rare case of atypical skull base meningioma with perineural spread

    PubMed Central

    Walton, Henry; Morley, Simon; Alegre-Abarrategui, Javier

    2015-01-01

    Atypical meningioma is a rare cause of perineural tumour spread. In this report, we present the case of a 46-year-old female with an atypical meningioma of the skull base demonstrating perineural tumour spread. We describe the imaging features of this condition and its distinguishing features from other tumours exhibiting perineural spread. PMID:27200171

  8. Radiation-induced meningioma after treatment for pituitary adenoma: Case report and literature review

    SciTech Connect

    Partington, M.D.; Davis, D.H. )

    1990-02-01

    Radiation-induced meningiomas are becoming increasingly well-recognized. We report a case of a 35-year-old man who developed a suprasellar meningioma 9 years after receiving a radiation dose of 4480 cGy for a pituitary adenoma. The literature is also reviewed. 10 references.

  9. Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

    PubMed Central

    Baldarçara, Leonardo; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P.; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Jörg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe

    2016-01-01

    Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine. PMID:25382714

  10. Recurrent rhabdoid meningioma with lymph node, pulmonary and bone metastases: a diagnostic and therapeutic challenge.

    PubMed

    Kakkar, Aanchal; Baghmar, Saphalta; Garg, Ajay; Suri, Vaishali; Raina, Vinod; Sarkar, Chitra; Sharma, Mehar Chand

    2016-07-01

    Rhabdoid meningioma is a rare meningioma variant, classified as WHO grade III. Although this tumor is known for its aggressive behavior and poor prognosis, extracranial metastasis is rare. We report the rare case of a 31-year-old patient with rhabdoid meningioma which recurred several times despite gross total resection, radiation therapy, and gamma knife radiosurgery, and the last recurrence was associated with metastases to lungs, lymph node and bone. The patient showed no response to paclitaxel-carboplatin, or vincristine-cyclophosphamide-adriamycin chemotherapy, and succumbed to the disease. Metastases from rhabdoid meningioma prove to be a diagnostic challenge, and treatment for metastatic meningiomas is not optimized, thus necessitating documentation and interdisciplinary consensus on management protocols. PMID:26875176

  11. Recurrent meningioma with malignant transformation: a case report and literature review

    PubMed Central

    Wang, Junwen; Wang, Lei; Luo, Bo; Chen, Zhi; Xiong, Zuojun; Fang, Mingbo; Li, Jun

    2015-01-01

    Meningiomas are common and mostly benign intracranial tumors, but may show a histological progression to malignancy. The mechanisms of malignant transformation remain unclear. Malignant meningiomas usually bear a high recurrence rate and unfavorable prognosis, and multiple surgical resections are required for the treatment. We report on a case of 51-year-old woman with a histologically benign intracranial meningioma. The patient had undergone multiple tumor resections and radiotherapy treatments. After multiple resections, the tumor demonstrated malignant transformation. A rapid tumor growth resulted in extensive tumor invasion of dura, brain and nasal sinus. Impaired brain function and subsequent intracranial hypertension caused serious headache, vomiting and coma. The patient survived 5 years following initial presentation. 3 subtotal resections of meningioma were performed. Radiotherapy was shown to be relatively ineffective during the course. The treatment strategies of recurrent meningiomas are briefly reviewed. PMID:26629232

  12. Brain meningioma with initial manifestation similar to cervical radiculopathy: a case report

    PubMed Central

    Huang, Yu-Hsuan; Hong, Chang-Zern; Wu, Wei-Ting; Li, Kun-Ta; Chou, Li-Wei

    2014-01-01

    Meningiomas are the most common benign brain tumors, and are characterized by slow growth and a long asymptomatic period. Once the tumor becomes symptomatic, the various presentations may be related to the location and compression of adjacent structures. Meningioma is primarily treated through surgical intervention, and thus earlier diagnosis is likely to result in better prognosis. The symptoms of the meningioma may mimic other diseases, making precise diagnosis difficult, which will then delay treatment. We report a case of brain meningioma that showed initial signs and symptoms similar to cervical radiculopathy. The symptoms extended gradually, and the ultimate diagnosis of meningioma was confirmed based on brain-image studies. After brain-tumor excision, postoperation radiotherapy, and aggressive rehabilitation, the patient was able to perform better in daily activities. PMID:25028552

  13. Malignant intrasellar meningioma presenting as an invasive pituitary macroadenoma: A rare case report and literature review

    PubMed Central

    ZHOU, PEIZHI; YIN, SENLIN; JIANG, SHU; CAI, BOWEN

    2016-01-01

    Intrasellar meningiomas are rare tumors that have the ability to mimic non-functioning pituitary adenomas. The majority of meningiomas are slow-growing and benign, therefore an intrasellar meningioma with malignant histological features is extremely rare. The present study describes the case of a malignant diaphragm meningioma that was controlled through combined chemotherapy, following subtotal surgical resection. The patient's symptoms ceased and no tumor recurrence was detected at the 3-year follow-up. Hormone levels were also observed as normal. Further investigation of similar cases may aid in achieving an accurate pre-operative diagnosis. This would prove particularly beneficial in regards to intrasellar meningiomas due to their specific location and surgical treatment. The present study analyzes the requirement of chemotherapy for the treatment of these unique tumors. PMID:26893694

  14. Iatrogenic Seeding of Tumor Cells in Thigh Soft Tissue Upon Surgical Removal of Intracranial Meningioma

    PubMed Central

    Maddah, Ghodratollah; Shabahang, Hossein; Zehi, Vahid; Sharifi Sistani, Nouriyeh; Mashhadi Nejad, Hossein

    2016-01-01

    Introduction: Meningioma is a benign and slowly-growing tumor that is responsible for 20% of brain neoplasms. It can be accompanied by some genetic disorders such as neurofibromatosis type 2 and is more common among women. As a space occupying lesion, it produces a wide range of signs and symptoms by compressing the adjacent and underlying tissues in the brain. Trauma and viruses are possible etiologies for meningioma. The ideal treatment of benign meningioma is surgical resection. Case Presentation: In this case report, we present a middle-aged man with a seeding metastasis of the cranial meningioma (after its removal) in the left thigh. During the removal operation, fascia lata had been used to repair the dura mater and the skin defect was repaired primarily. Conclusion: We believe that the occurrence of meningioma at the site of incision in the thigh is related to using the same surgical instruments for the removal of the brain tumor. PMID:27303610

  15. Primary intraosseous atypical inflammatory meningioma presenting as a lytic skull lesion: Case report with review of literature.

    PubMed

    Bohara, Sangita; Agarwal, Swapnil; Khurana, Nita; Pandey, P N

    2016-01-01

    Primary extradural meningiomas of the skull comprise 1% of all meningiomas, and lytic skull meningiomas are still rarer and are said to be more aggressive. We present a case of 38-year-old male with an extradural tumor which on histopathological examination showed features of inflammatory atypical meningioma (WHO Grade II). The intense inflammatory nature of osteolytic primary intraosseous meningioma has not been reported before. This entity deserves special mention because of the need for adjuvant therapy and proper follow-up. PMID:27510685

  16. Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

    PubMed Central

    Huang, Yin-Cheng; Wei, Kuo-Chen; Chang, Chen-Nen; Chen, Pin-Yuan; Hsu, Peng-Wei; Chen, Carl P.; Lu, Chin-Song; Wang, Hung-Li; Gutmann, David H.; Yeh, Tu-Hsueh

    2014-01-01

    Most meningiomas are benign, but some clinical-aggressive tumors exhibit brain invasion and cannot be resected without significant complications. To identify molecular markers for these clinically-aggressive meningiomas, we performed microarray analyses on 24 primary cultures from 21 meningiomas and 3 arachnoid membranes. Using this approach, increased transglutaminase 2 (TGM2) expression was observed, which was subsequently validated in an independent set of 82 meningiomas by immunohistochemistry. Importantly, the TGM2 expression level was associated with increasing WHO malignancy grade as well as meningioma recurrence. Inhibition of TGM2 function by siRNA or cystamine induced meningioma cell death, which was associated with reduced AKT phosphorylation and caspase-3 activation. Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth. PMID:25247996

  17. Implications on cerebellar function from information coding.

    PubMed

    Huang, Chiming

    2008-01-01

    One function of the cerebellar cortex is to process information. There are at least two types of information. Temporal information is encoded in the timing pattern of action and synaptic potentials, whereas structural information is encoded in the spatial pattern of the cerebellar synaptic circuitry. Intuitively, analysis of highly complex information in the time domain would require a cerebellar cortex with structural complexity to match. Information theory offers a way to estimate quantitatively both types of information and thereby helps to test hypotheses or advance theories of cerebellar neurobiology. These estimates suggest: (i) That the mossy-fiber-granule-cell system carries far more (temporal) information than the climbing fiber system, (ii) that Purkinje cells extract only a fraction of the (temporal) information from their afferents, and (iii) that the cerebellar cortex has a large (spatial) information coding capacity. Concerning information, one can argue that the cerebellar cortex analyzes temporal information in its afferents as a search engine, in search of coincidental mossy fiber events based on timing cues provided by climbing fiber events. Results of successive searches are continuously being converted into structural information encoded in the spatial distribution pattern of granule-cell-Purkinje-cell synapses along granule cell axons, thereby providing an adaptive and indeed self-correcting dimension to the structural information code. The search engine operation involves cellular mechanisms acting on temporal events and is part of an associative learning process. The conversion and generation of structural information involves neuroplasticity mechanisms acting at the synaptic level, with electrophysiological as well as structural consequences, and may be part of the short- and long-term memory process. These and other attributes qualify the cerebellar cortex as a dynamic information processing center, contributing to memory and learning while

  18. Posterolateral approach for spinal intradural meningioma with ventral attachment

    PubMed Central

    Takami, Toshihiro; Naito, Kentaro; Yamagata, Toru; Yoshimura, Masaki; Arima, Hironori; Ohata, Kenji

    2015-01-01

    Background: Spinal meningioma with ventral attachment is a challenging pathology. Several technical modifications have been proposed to secure safe and precise resection of these tumors. Materials and Methods: This retrospective study focused on the precise and safe surgery of spinal meningiomas with strictly ventral attachment of cervical or thoracic spine. The surgical technique included a lateral oblique position for the patient, laminectomy with unilateral medial facetectomy on the tumor side, and spinal cord rotation with the dentate ligament. The neurological status of patients was assessed using the modified McCormick functional schema (mMFS) and sensory pain scale (SPS) before and at least 3 months after surgery. Patients were followed-up for a mean of 23.7 months. Tumor removal was graded using the Simpson grade for removal of meningiomas, and the extent of excision was confirmed using early postoperative magnetic resonance imaging. Results: Simpson grade 1 or 2 resections were achieved in all cases. No major surgery-related complications were encountered, postoperatively. The mean mMFS score before surgery was 3.1, improving significantly to 1.7 after surgery (P < 0.05). The mean SPS score before surgery was 2.4, improving significantly to 1.6 after surgery (P < 0.05). Conclusions: This surgical technique offers a posterolateral surgical corridor to the ventral canal of both cervical and thoracic spine. The present preliminary analysis suggests that functional outcomes were satisfactory with minimal surgery-related complications, although considerable surgical experience is needed to achieve a high level of surgical confidence. PMID:26692694

  19. Slack brain in meningioma surgery through lateral supraorbital approach

    PubMed Central

    Romani, Rossana; Silvasti-Lundell, Marja; Laakso, Aki; Tuominen, Hanna; Hernesniemi, Juha; Niemi, Tomi

    2011-01-01

    Background: Surgery of skull base meningiomas by the lateral supraorbital (LSO) approach requires relaxed brain. Therefore, we assessed combined effects of the elements of neuroanesthesia on neurosurgical conditions during craniotomy. Methods: The anesthesiological and surgical charts of 66 olfactory groove, 73 anterior clinoidal, and 52 tuberculum sellae meningioma patients operated on by the senior author (J.H.) at the Department of Neurosurgery of Helsinki University Central Hospital, Helsinki, Finland, between September 1997 and August 2010, were retrospectively analyzed. Results: One-hundred fifty-four (82%) patients had good surgical conditions, and this was achieved by (1) elevating the head 20 cm above the cardiac level in all patients with only slightly lateral turn or neck flexion, (2) administering mannitol preoperatively in medium or large meningiomas (n = 60), (3) maintaining anesthesia with propofol infusion (n = 46) or volatile anesthetics (n = 107) also in patients with large tumors (n = 37), and (4) controlling intraoperative hemodynamics. Brain relaxation was satisfactory in 18 (10%) and poor in 15 (8%) patients. The median intraoperative blood loss was 200 (range, 0-2000) ml. Only 9% of patients received red blood cell transfusion. The median time to extubation was 18 (range, 8-105) min after surgery. Extubation time correlated with the patients’ preoperative clinical status and the size of tumor but not with the modality of anesthesia. Conclusions: Slack brain during the LSO approach is achieved by correct patient positioning, preoperative mannitol, either by propofol or in small tumors inhaled anesthetics, and optimizing cerebral perfusion pressure. Under these circumstances, intraoperative brain swelling is prevented, bleeding is minimal, and no blood transfusions are needed. PMID:22145086

  20. Oculomotor studies of cerebellar function in autism.

    PubMed

    Nowinski, Caralynn V; Minshew, Nancy J; Luna, Beatriz; Takarae, Yukari; Sweeney, John A

    2005-11-15

    Histopathological, neuroimaging and genetic findings indicate cerebellar abnormalities in autism, but the extent of neurophysiological dysfunction associated with those findings has not been systematically examined. Suppression of intrusive saccades (square wave jerks) and the ability to sustain eccentric gaze, two phenomena requiring intact cerebellar function, were examined in 52 high-functioning individuals with autism and 52 age- and IQ-matched healthy subjects during visual fixation of static central and peripheral targets. Rates of intrusive saccades were not increased in autism during visual fixation, and foveopetal ocular drift was also not increased when subjects held an eccentric gaze. The absence of gross disturbances of visual fixation associated with cerebellar disease in individuals with autism, such as increased square wave jerk rates and foveopetal drift when holding eccentric gaze, indicates that the functional integrity of cerebellar--brainstem networks devoted to oculomotor control is preserved in autism despite reported anatomic variations. However, increased amplitude of intrusive saccades and reduced latency of target refixation after intrusive saccades were observed in individuals with autism, especially when subjects maintained fixation of remembered target locations without sensory guidance. The atypical metrics of intrusive saccades that were observed may be attributable to faulty functional connectivity in cortico-cerebellar networks. PMID:16214219

  1. Cerebellar modules operate at different frequencies

    PubMed Central

    Zhou, Haibo; Lin, Zhanmin; Voges, Kai; Ju, Chiheng; Gao, Zhenyu; Bosman, Laurens WJ; Ruigrok, Tom JH; Hoebeek, Freek E

    2014-01-01

    Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depend on activation of TRPC3, and that this property is relevant for all cerebellar functions. DOI: http://dx.doi.org/10.7554/eLife.02536.001 PMID:24843004

  2. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  3. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    MedlinePlus

    ... Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/collapse boxes. ... Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by progressive problems ...

  4. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  5. Diagnosis and Management of Hereditary Meningioma and Vestibular Schwannoma.

    PubMed

    Shaw, Adam

    2016-01-01

    Bilateral vestibular schwannomata and meningiomata are the tumours most commonly associated with neurofibromatosis type II (NF2). These tumours may also be seen in patients with schwannomatosis and familial meningioma, but these phenotypes are usually easy to distinguish. The main diagnostic challenge when managing these tumours is distinguishing between sporadic disease which carries low risk of subsequent tumours or NF2 with its associated morbidities and reduced life expectancy. This chapter outlines some of the diagnostic and management considerations along with associated evidence. PMID:27075346

  6. Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series

    PubMed Central

    Lou, Emil; Sumrall, Ashley L.; Turner, Scott; Peters, Katherine B.; Desjardins, Annick; Vredenburgh, James J.; McLendon, Roger E.; Herndon, James E.; McSherry, Frances; Norfleet, Julie; Friedman, Henry S.

    2012-01-01

    Intracranial meningiomas are often indolent tumors which typically grow over years to decades. Nonetheless, meningiomas that progress after maximum safe resection and radiation therapy pose a significant therapeutic challenge and effective therapies have yet to be identified. Preclinical studies implicate angiogenesis in the pathophysiology of more aggressive meningiomas, suggesting that anti-angiogenic therapies may be of utility in this setting. We performed a retrospective review of fourteen patients with recurrent meningioma treated at Duke University Medical Center with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, administered either alone or in combination with chemotherapy. Most patients were heavily pre-treated. Progression-free survival at 6 months was 86 % and was comparable regardless of meningioma grade and whether bevacizumab was administered as monotherapy or in combination with chemotherapy. Most toxicities were mild however single patients developed CNS hemorrhage (grade 1) and intestinal perforation (grade 4), respectively. Bevacizumab can be administered safely to patients with meningioma and appears to be associated with encouraging anti-tumor effect when administered as either a single agent or in combination with chemotherapy. Phase II trials investigating bevacizumab in patients with progressive/recurrent meningioma are warranted. PMID:22535433

  7. Prognostic Implication of Preoperative Behavior Changes in Patients with Primary High-Grade Meningiomas

    PubMed Central

    2014-01-01

    High-grade meningiomas are rare extra-axial tumors, frequently causing brain invasion and prominent brain edema. Patients harboring high-grade meningiomas occasionally present with behavior changes. Data about frequency and prognostic importance of preoperative behavior changes in patients with high-grade meningiomas is missing. 86 patients with primary high-grade meningiomas were analyzed. Statistical analysis was performed to determine correlation of preoperative behavior changes with tumor location, preoperative brain edema, tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain invasion. Survival analysis was performed. 30 (34.9%) patients presented with preoperative behavior changes. These changes were more frequent with male patients (P = 0.066) and patients older than 55 years (P = 0.018). They correlated with frontal location (P = 0.013), tumor size (P = 0.023), microscopic brain invasion (P = 0.015), and brain edema (P = 0.006). Preoperative behavior changes did not correlate with duration of symptoms, tumor cleavability, tumor malignancy grade, and Ki67 proliferation index. They were not significantly related to overall survival or recurrence-free survival of patients with primary high-grade meningiomas. Preoperative behavior changes are frequent in patients harboring primary high-grade meningiomas. They correlate with tumor size, microscopic brain invasion, and brain edema. Preoperative behavior changes do not predict prognosis in patients with primary high-grade meningiomas. PMID:24578632

  8. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema.

    PubMed

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten; Thomsen, Carsten; Juhler, Marianne; Laursen, Henning; Broholm, Helle

    2011-12-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined. Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p < 0.05). The capillary length in the meningiomas was positively correlated to the PTBE (p = 0.038). If VEGF is responsible for the formation of PTBE, the edema may be treated with the anti-VEGF drug Bevacizumab (Avastin), which has been shown to reduce PTBE in patients with glioblastoma multiforme. PMID:22085359

  9. Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

    PubMed Central

    Pećina-Šlaus, Nives; Kafka, Anja; Lechpammer, Mirna

    2016-01-01

    Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed. PMID:27429002

  10. A new texture and shape based technique for improving meningioma classification.

    PubMed

    Fatima, Kiran; Arooj, Arshia; Majeed, Hammad

    2014-11-01

    Over the past decade, computer-aided diagnosis is rapidly growing due to the availability of patient data, sophisticated image acquisition tools and advancement in image processing and machine learning algorithms. Meningiomas are the tumors of brain and spinal cord. They account for 20% of all the brain tumors. Meningioma subtype classification involves the classification of benign meningioma into four major subtypes: meningothelial, fibroblastic, transitional, and psammomatous. Under the microscope, the histology images of these four subtypes show a variety of textural and structural characteristics. High intraclass and low interclass variabilities in meningioma subtypes make it an extremely complex classification problem. A number of techniques have been proposed for meningioma subtype classification with varying performances on different subtypes. Most of these techniques employed wavelet packet transforms for textural features extraction and analysis of meningioma histology images. In this article, a hybrid classification technique based on texture and shape characteristics is proposed for the classification of meningioma subtypes. Meningothelial and fibroblastic subtypes are classified on the basis of nuclei shapes while grey-level co-occurrence matrix textural features are used to train a multilayer perceptron for the classification of transitional and psammomatous subtypes. On the whole, average classification accuracy of 92.50% is achieved through the proposed hybrid classifier; which to the best of our knowledge is the highest. PMID:25060536

  11. Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.

    PubMed

    Yang, Hong Wei; Kim, Tae-Min; Song, Sydney S; Shrinath, Nihal; Park, Richard; Kalamarides, Michel; Park, Peter J; Black, Peter M; Carroll, Rona S; Johnson, Mark D

    2012-01-01

    Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas. PMID:22355270

  12. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations

    PubMed Central

    Brastianos, Priscilla K.; Horowitz, Peleg M.; Santagata, Sandro; Jones, Robert T.; McKenna, Aaron; Getz, Gad; Ligon, Keith L.; Palescandolo, Emanuele; Van Hummelen, Paul; Ducar, Matthew D.; Raza, Alina; Sunkavalli, Ashwini; MacConaill, Laura E.; Stemmer-Rachamimov, Anat O.; Louis, David N.; Hahn, William C.; Dunn, Ian F.; Beroukhim, Rameen

    2013-01-01

    Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of meningiomas1 but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas exhibited simple genomes, with fewer mutations, rearrangements, and copy-number alterations than reported in other adult tumors. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers among an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (E17K) and SMO (W535L) and exhibited immunohistochemical evidence of activation of their pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets. PMID:23334667

  13. Endoscopic Endonasal Approach for Transclival Resection of a Petroclival Meningioma: A Technical Note

    PubMed Central

    Jean, Walter C; Anaizi, Amjad; DeKlotz, Timothy R

    2016-01-01

    The endoscopic endonasal transclival approach has been widely described for its use to resect clivus chordomas, but there have only been isolated reports of its use for petroclival meningiomas. These tumors are most often resected utilizing open transpetrosal approaches, but these operations, difficult even in the hands of dedicated skull base surgeons, are particularly challenging if the meningiomas are medially-situated and positioned mainly behind the clivus. For this subset of petroclival meningiomas, a transclival approach may be preferable. We report a meningioma resected via an endoscopic endonasal transclival technique. The patient was a 63-year-old man who presented originally for medical attention because of diplopia related to an abducens palsy on the left. A workup at that time revealed a meningioma contained entirely in the left cavernous sinus, and this was treated with stereotactic radiosurgery. His symptoms resolved and his meningioma was stable on MRI for several years after treatment. The patient was then lost to follow-up until 13 years after radiosurgery when he experienced intermittent diplopia again. At this point, workup revealed a large petroclival meningioma compressing the brainstem. He underwent a successful endoscopic endonasal transclival resection of this tumor. A demonstration of the step-by-step surgical technique, discussion of the nuances of the operation, and a comparison with the open transpetrosal approaches are included in our report. PMID:27433420

  14. Reduced Allergy and Immunoglobulin E among Adults with Intra-cranial Meningioma Compared to Controls

    PubMed Central

    Wiemels, Joseph L.; Wrensch, Margaret; Sison, Jennette D.; Zhou, Mi; Bondy, Melissa; Calvocoressi, Lisa; Black, Peter M.; Yu, Herbert; Schildkraut, Joellen M.; Claus, Elizabeth B.

    2012-01-01

    Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51 – 0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75–0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. Since some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted. PMID:21520030

  15. Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Lechpammer, Mirna

    2016-01-01

    Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed. PMID:27429002

  16. Landmark Based Shape Analysis for Cerebellar Ataxia Classification and Cerebellar Atrophy Pattern Visualization

    PubMed Central

    Yang, Zhen; Abulnaga, S. Mazdak; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi; Ying, Sarah H.; Prince, Jerry L.

    2016-01-01

    Cerebellar dysfunction can lead to a wide range of movement disorders. Studying the cerebellar atrophy pattern associated with different cerebellar disease types can potentially help in diagnosis, prognosis, and treatment planning. In this paper, we present a landmark based shape analysis pipeline to classify healthy control and different ataxia types and to visualize the characteristic cerebellar atrophy patterns associated with different types. A highly informative feature representation of the cerebellar structure is constructed by extracting dense homologous landmarks on the boundary surfaces of cerebellar sub-structures. A diagnosis group classifier based on this representation is built using partial least square dimension reduction and regularized linear discriminant analysis. The characteristic atrophy pattern for an ataxia type is visualized by sampling along the discriminant direction between healthy controls and the ataxia type. Experimental results show that the proposed method can successfully classify healthy controls and different ataxia types. The visualized cerebellar atrophy patterns were consistent with the regional volume decreases observed in previous studies, but the proposed method provides intuitive and detailed understanding about changes of overall size and shape of the cerebellum, as well as that of individual lobules. PMID:27303111

  17. Landmark based shape analysis for cerebellar ataxia classification and cerebellar atrophy pattern visualization

    NASA Astrophysics Data System (ADS)

    Yang, Zhen; Abulnaga, S. Mazdak; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    Cerebellar dysfunction can lead to a wide range of movement disorders. Studying the cerebellar atrophy pattern associated with different cerebellar disease types can potentially help in diagnosis, prognosis, and treatment planning. In this paper, we present a landmark based shape analysis pipeline to classify healthy control and different ataxia types and to visualize the characteristic cerebellar atrophy patterns associated with different types. A highly informative feature representation of the cerebellar structure is constructed by extracting dense homologous landmarks on the boundary surfaces of cerebellar sub-structures. A diagnosis group classifier based on this representation is built using partial least square dimension reduction and regularized linear discriminant analysis. The characteristic atrophy pattern for an ataxia type is visualized by sampling along the discriminant direction between healthy controls and the ataxia type. Experimental results show that the proposed method can successfully classify healthy controls and different ataxia types. The visualized cerebellar atrophy patterns were consistent with the regional volume decreases observed in previous studies, but the proposed method provides intuitive and detailed understanding about changes of overall size and shape of the cerebellum, as well as that of individual lobules.

  18. Intracranial meningiomas managed at Memfys hospital for neurosurgery in Enugu, Nigeria

    PubMed Central

    Mezue, Wilfred C; Ohaegbulam, Samuel C; Ndubuisi, Chika C; Chikani, Mark C; Achebe, David S

    2012-01-01

    Introduction: The epidemiology and pathology of meningioma in Nigeria are still evolving and little has been published about this tumor in Nigeria, especially in the southeast region. The aim of this paper is to compare the characteristics of intracranial meningioma managed in our center with the pattern reported in the literature worldwide. Materials and Methods: Retrospective analysis of prospectively recorded data of patients managed for intracranial meningioma between January 2002 and December 2010 at a Private neurosurgery Hospital in Enugu, Nigeria. We excluded patients whose histology results were inconclusive. Results: Meningiomas constituted 23.8% of all intracranial tumors seen in the period. The male to female ratio was 1:1.1. The peak age range for males and females were in the fifth and sixth decades, respectively. The most common location is the Olfactory groove in 26.5% of patients followed by convexity in 23.5%. Presentation varied with anatomical location of tumor. Patients with olfactory groove meningioma (OGM) mostly presented late with personality changes and evidence of raised ICP. Tuberculum sellar and sphenoid region tumors presented earlier with visual impairment with or without hormonal abnormalities. Seizures occurred in 30.9% of all patients and in 45% of those with convexity meningiomas. Only 57.4% of the patients were managed surgically and there was no gender difference in this group. WHO grade1 tumors were the most common histological types occurring in 84.6%. One patient had atypical meningioma and two had anaplastic tumors. Conclusion: The pattern of meningioma in our area may have geographical differences in location and histology. Childhood meningioma was rare. PMID:23188985

  19. GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.

    PubMed

    Piaskowski, S; Rieske, P; Szybka, M; Wozniak, K; Bednarek, A; Płuciennik, E; Jaskolski, D; Sikorska, B; Liberski, Pawel Piotr

    2005-10-01

    Deletions of 1p occur in approximately 30% of meningiomas. Based on loss of heterozygosity (LOH) analysis, two regions on 1p have been suspected to be carriers of tumor suppressor genes. We chose the GADD45A and EPB41 genes as tumor suppressor candidates based on their function and chromosomal localization. We analyzed 19 cases of meningioma with LOH of 1p by means of sequencing of the GADD45A gene and Western blotting of the GADD45a protein. Twenty cases of meningioma without 1p LOH were also analyzed by Western blotting to find out if changes of the GADD45a protein expression occurred. Nineteen samples with 1p LOH (12 grade I; 7 grade II, WHO classification) and 20 samples without 1p LOH (18 grade I; 2 grade II) were also analyzed by means of real-time polymerase chain reaction to find abnormalities in EPB41 mRNA levels in meningioma. LOH analysis was performed using seven microsatellite markers: D1S508 (1p36.2), D1S199 (1p36.1) D1S2734 (1p36.1), D1S2720 (1p34), D1S197 (1p32), D1S162 (1p32), D1S429 (1p11). LOH analysis confirmed previously described localization of putative tumor suppressor genes on 1p and involvement in meningioma pathogenesis (1p36 and 1p32). The open reading frame of GADD45A and intron splicing sites showed neither mutations nor polymorphisms. GADD45a protein molecular weight and expression level were unaltered in meningiomas with and without 1p LOH. We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. EPB41 gene expression was unchanged in all analyzed meningiomas. This suggests that involvement of the EPB41 gene (4.1R protein) in meningioma pathogenesis should be reconsidered. PMID:16157202

  20. DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence.

    PubMed

    Menghi, Francesca; Orzan, Francesca N; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca; Finocchiaro, Gaetano

    2011-01-01

    Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted. PMID:21948653

  1. Role of HER-2 activity in the regulation of malignant meningioma cell proliferation and motility.

    PubMed

    Wang, Weijia; Tu, Yi; Wang, Shanshan; Xu, Shan; Xu, Linlin; Xiong, Yifeng; Mei, Jinhong; Wang, Chunliang

    2015-09-01

    Meningiomas are common types of intracranial tumor. Invasive and malignant meningiomas present a significant therapeutic challenge due to high rates of recurrence and invasion. Understanding the molecular mechanism of invasion may assist in designing novel therapeutic approaches and improving patient survival rates. The HER‑2 gene has been demonstrated to be a useful predictor of tumor aggression, which promotes the survival and growth of cancer cells through the mitogen‑activated protein kinase and/or phosphatidylinositol 3‑kinase (PI3K)/AKT pathway. Until now, few studies have investigated the associateion between meningiomas and the expression of HER‑2, and the significance of HER‑2 in meningiomas remains to be elucidated. The present study aimed to investigate the effects of the HER‑2 gene on the biological behaviors of human malignant meningioma cells. The results demonstrated that downregulation of the expression of HER‑2 by small interfering RNA in human meningioma cells significantly inhibited cell motility and proliferation, led to cell cycle arrest at the G0/G1‑phase and increased early apoptosis. By contrast, the overexpression of HER‑2 group resulted in meningioma cell invasion, migration and proliferation being significantly enhanced, cell cycle was promoted at the G1/S‑phase and early apoptosis was decreased. Accordingly, the inhibition of HER‑2 also prevented the protein expression of PI3K and phosphorylated AKT. The results demonstrated that regulation of the HER‑2 gene can affect the proliferation, apoptosis, invasion and metastasis abilities of human meningioma cells in vitro. Furthermore, PI3K/AKT may contribute to the carcinogenesis and development of human meningiomas in combination with HER-2. PMID:25998419

  2. Cerebellar contribution to feedforward control of locomotion

    PubMed Central

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing—the process that allows spatial and temporal relationships between events to be recognized—has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed. PMID:25009490

  3. [Residual cerebellar ataxia following acute phenytoin intoxication].

    PubMed

    Awada, A; Amene, P; al Jumah, M; al Beladi, K

    1999-04-01

    A 30-year-old man was given high doses of phenytoin together with 4 antituberculous drugs for a seizure associated with a probable brain tuberculoma. He developed hepatic toxicity and his serum phenytoin reached the high level of 298 mumol/l (therapeutic range 40-79 mumol/l). All drugs were stopped and the biological parameters returned progressively to normal over the next 15 days. However, he remained with a cerebellar axial syndrome and was still severely ataxic 2 months later. Brain CT and MRI showed mild cerebellar atrophy. This case and the few other published ones, together with some recent experimental data, show that high doses of phenytoin can be toxic to the cerebellar cortical cells. The rarity of similar cases, while millions of epileptics are under phenytoin treatment, would however suggest that individual susceptibility may play a role in this toxicity. PMID:10367328

  4. Cerebellar Glioblastoma Multiforme in an Adult

    PubMed Central

    Hur, Hyuk; Jung, Tae-Young; Kim, In-Young

    2008-01-01

    Primary cerebellar glioblastoma multiforme (GBM) is a rare tumor in adults that accounts for just 1% of all cases of GBM. Due to their rarity, cerebellar GBMs are not yet completely understood about the pathogenesis and the prognosis. Here, we present a case of GBM in a 69-year-old man. Neurologic examination revealed the presence of cerebellar signs. Magnetic resonance imaging (MRI) showed a 4.5 × 3.6 cm-sized, ill-defined, heterogeneously enhancing mass in the left cerebellum and two patchy hyperintense lesions in the right cerebellum with minimal enhancement. After operation, glioblastoma was histologically confirmed. Postoperative radiotherapy with concomitant and adjuvant temozolomide chemotherapy was subsequently followed. Here, a case of unusual GBM in the cerebellum is reported with review of literature regarding the pathogenesis, the differential diagnosis and prognosis. There was no evidence of recurrence during postoperative one year. This patient showed a good prognosis in spite of the multiple lesions. PMID:19096643

  5. Cerebellar contribution to feedforward control of locomotion.

    PubMed

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing-the process that allows spatial and temporal relationships between events to be recognized-has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed. PMID:25009490

  6. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted cerebellar stimulator. 882.5820 Section... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted cerebellar stimulator. (a) Identification. An implanted cerebellar stimulator is a device used to...

  7. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted cerebellar stimulator. 882.5820 Section... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted cerebellar stimulator. (a) Identification. An implanted cerebellar stimulator is a device used to...

  8. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted cerebellar stimulator. 882.5820 Section... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted cerebellar stimulator. (a) Identification. An implanted cerebellar stimulator is a device used to...

  9. Imaging of cervical extradural en-plaque meningioma. A case report.

    PubMed

    D'Amico, A; Napoli, M; Cirillo, M; D'Arco, F; D'Anna, G; Caranci, F; Mariniello, G; Brunetti, A

    2012-11-01

    Meningioma is one of the most common spinal extramedullary tumors, largely intradural. An extradural localization is possible but less frequent. There are two morphologically different types of meningioma: one is round, and the other is the "en-plaque" form, that grows along the dura mater like a sheet. The "en-plaque" form, is unusual. We report on an unusual case of epidural and extraspinal "en-plaque" meningioma, describing the MRI and CT features and discussing the possible principal differential diagnosis (neurolymphomatosis, plexiform neurofibromas/schwannomas and metastasis). PMID:24029096

  10. Endoscopic Endonasal Approach to Ventral Posterior Fossa Meningiomas: From Case Selection to Surgical Management.

    PubMed

    Beer-Furlan, André; Vellutini, Eduardo A S; Balsalobre, Leonardo; Stamm, Aldo C

    2015-07-01

    Clival, petroclival, and foramen magnum meningiomas are challenging lesions to manage independently of the selected surgical approach. The expanded endoscopic endonasal approach (EEA) provided a safe alternative on the armamentarium of skull base approaches. There is a paucity of literature regarding endoscopic management of meningiomas because of certain limiting factors, including rarity of the pathologic condition, technical challenges, expertise of the surgical team, and available resources. The surgical technique, possible complications, and postoperative care are described in detail. This article highlights the important aspects in choosing this surgical approach and managing ventral posterior fossa meningiomas through the EEA. PMID:26141360

  11. A case of a temporal bone meningioma presenting as a serous otitis media

    PubMed Central

    De Foer, Bert; Bernaerts, Anja; Van Dinther, Joost; Parizel, Paul M

    2014-01-01

    We report the imaging features of a case of a temporal bone meningioma extending into the middle ear cavity and clinically presenting as a serous otitis media. Temporal bone meningioma extending in the mastoid or the middle ear cavity, however, is very rare. In case of unexplained or therapy-resistant serous otitis media and a nasopharyngeal tumor being ruled out, a temporal bone computed tomography (CT) should be performed. If CT findings are suggestive of a temporal bone meningioma, a magnetic resonance imaging (MRI) examination with gadolinium will confirm diagnosis and show the exact extension of the lesion. PMID:25535569

  12. Extra-axial isolated cerebral varix misdiagnosed as convexity meningioma

    PubMed Central

    Tan, Zhi-Gang; Zhou, Qian; Cui, Yan; Yi, Lei; Ouyang, Yian; Jiang, Yugang

    2016-01-01

    Abstract Isolated cerebral varix is a rare cerebrovascular anomaly, which is easily misdiagnosed as other brain tumors. A 59-year-old female patient with noncontributory medical history presented with headache and insomnia for the last 2 months. Upon admission, her neurological examination was unremarkable. Magnetic resonance imaging revealed a well-demarcated extra medullary mass, 11 × 11 mm in size, within the subdural space at the right frontal lobe. The lesion was initially interpreted as a convexity meningioma. After conducting a craniotomy on the patient, an extra-axial varix was exposed and resected subsequently. The patient's headache was resolved soon after surgery and charged without neurologic sequelae. Extra-axial isolated cerebral varix is mimicking convexity meningioma on MR images and should be considered as a differential diagnosis. The focal erosion in the inner table of the skull could be an important character of extra-axial isolated cerebral varix. An extremely round shape and smooth contour of the lesion was another important character. Isolated cerebral varix is rare vascular lesion that is treated surgically in the case of rupture or compression of adjacent structures. The information obtained with noninvasive imaging techniques should include CTA to make a clinical decision. PMID:27368037

  13. Cerebral venous malformation with meningioma: A case report

    PubMed Central

    MU, QINGCHUN; ZHANG, KUN; WANG, JUSTIN; SAYARI, ARASH; HUANG, HAIYAN

    2016-01-01

    A 43-year-old female patient was admitted to The First Hospital of Jilin University (Changchun, China) on 1st October 2011 with a 10-day history of discontinuous, whole-brain headache and a 1-year history of impaired vision and memory deterioration, accompanied by right facial numbness. Clinical signs and radiological features observed using magnetic resonance imaging (MRI) led to the diagnosis of an intracranial meningioma accompanied by a cerebral venous malformation (CVM). The patient underwent neurosurgical resection of the meningioma, but required no further treatment for the CVM. At a 1-year follow-up examination, the patient continued to complain of discontinuous headache. Digital subtraction angiography (DSA) was used to reconfirm the CVM diagnosis; however, no treatment was administered due to the high risks of treatment and only mild symptoms experienced by the patient. The present case demonstrates the efficacy of DSA for detecting the presence and specific nature of CVM, and compares the value of MRI and DSA in the diagnosis of CVM. The majority of CVM patients exhibit no clinical symptoms, and the disease prognosis is typically favorable. PMID:26998016

  14. Unilateral facial myokymia in a dog with an intracranial meningioma.

    PubMed

    Holland, C T; Holland, J T; Rozmanec, M

    2010-09-01

    A 23-month-old castrated male Cavalier King Charles spaniel was evaluated because of a 6-month history of unusual rippling/undulating movements of the right facial muscles that were continuous and persisted during sleep. Neurological examination revealed narrowing of the right palpebral fissure and unilateral right-sided facial myokymia that was characterised by myokymic, and to a lesser degree, neuromyotonic discharges on concentric needle electromyographic examination. After persisting unchanged for almost 2.5 years from its onset, the facial myokymia gradually disappeared over a 6-month period concomitant with the emergence of a persistent ipsilateral facial paralysis and head tilt. At 5 years and 9 months after the first examination, signs of ipsilateral lacrimal, pharyngeal and laryngeal dysfunction became evident and the dog was euthanased. Postmortem examination identified a malignant (WHO grade III) meningioma in the right cerebellopontomedullary angle that compressed the ventrolateral cranial medulla, effaced the jugular foramen and internal acoustic meatus and extended into the facial canal of the petrous temporal bone. Novel findings were the unique observation of isolated unilateral facial myokymia preceding diagnosis of a meningioma affecting facial nerve function within the caudal cranial fossa and the remarkably long duration of neurological signs (75 months) attributable to the neoplasm. PMID:20726972

  15. Rare Presentation of Metastatic Prostate Adenocarcinoma as a Meningioma Mimic

    PubMed Central

    Rahmathulla, Gazanfar; Prayson, Richard A.; Weil, Robert J.

    2014-01-01

    Background Dural lesions in the anterior skull base may occur secondary to benign or malignant pathology that may be difficult to differentiate on imaging. Detailed clinical evaluation in many cases will narrow the differential diagnosis. In spite of using all the available information, in certain cases the underlying etiology of a lesion remains unclear. Participant We report a rare case of metastatic prostate adenocarcinoma to a meningioma in a 67-year-old-man who presented with progressive confusion and mental status alterations with no prior history of malignancy. Neuroimaging revealed a large anterior skull base lesion. Results The lesion was surgically resected, and histopathology revealed a collision tumor, in which prostate adenocarcinoma was found admixed with a World Health Organization grade I meningioma. Conclusion Anterior dural skull base lesions can be either benign or malignant. Although infrequently reported, a benign-appearing dural-based lesion may be a manifestation of an underlying malignancy, and a thorough clinical, radiologic, and pathologic examination may be necessary, especially in the elderly. PMID:25083396

  16. The Cerebellar Mutism Syndrome and Its Relation to Cerebellar Cognitive Function and the Cerebellar Cognitive Affective Disorder

    ERIC Educational Resources Information Center

    Wells, Elizabeth M.; Walsh, Karin S.; Khademian, Zarir P.; Keating, Robert F.; Packer, Roger J.

    2008-01-01

    The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is…

  17. Regression of Intracranial Meningioma during Treatment with α1-Adrenoceptor Blocker

    PubMed Central

    Hoegestoel, Einar August; Berg-Johnsen, Jon

    2016-01-01

    Background Regression of meningioma has been reported after hemorrhage or hormonal withdrawal. Here, we report a case of an incidentally diagnosed meningioma that regressed in association with α1-adrenoceptor antagonist. Case report A 59-year old male patient with an incidentally diagnosed lateral sphenoid wing meningioma was followed with serial magnetic resonance imaging. The tumor with a maximum diameter of 43 mm showed progressive regression, and after 3 years the size was reduced to 22% of the initial volume. During follow-up the patient was treated with an α1-adrenoceptor antagonist (tamsulosin) for benign prostatic hyperplasia. Possible mechanisms are discussed, including our main hypothesis of reduced mitogenic effects through phospholipase C-signal transduction. Conclusion This is the first report of regression of an incidentally diagnosed meningioma associated with α1-adrenoceptor antagonist treatment. PMID:27175325

  18. Unilateral vocal cord palsy and dysphagia: an unusual presentation of cerebellopontine angle meningioma.

    PubMed

    Senior, Andrew; Douglas, James Andrew; Thompson, Stuart

    2015-01-01

    Cerebellopontine angle (CPA) tumours are the most common neoplasms in the posterior fossa, accounting for 5-10% of intracranial tumours. Most CPA tumours are benign, with most being vestibular schwannomas. Meningiomas arising from the jugular foramen are among the rarest of all with very few being described in the literature. Treatment options vary considerably as experience with these tumours is limited. One option is a skull base approach, but this depends on size, location and ability to preserve lower cranial nerve function. This can be extremely challenging and is accompanied by high mortality risk; therefore, a more conservative option must be considered. This case report highlights the difficulty in management of patients with jugular fossa meningiomas, including appropriate investigations, analysis of surgical versus conservative treatment and associated complications. Furthermore, we elaborate the decision-making process pertaining to the tailoring of the surgical route used for the resection of jugular foramen meningiomas. (Jugular Foramen Meningioma, cerebellopontine angle). PMID:26486157

  19. Unilateral vocal cord palsy and dysphagia: an unusual presentation of cerebellopontine angle meningioma

    PubMed Central

    Senior, Andrew; Douglas, James Andrew; Thompson, Stuart

    2015-01-01

    Cerebellopontine angle (CPA) tumours are the most common neoplasms in the posterior fossa, accounting for 5–10% of intracranial tumours. Most CPA tumours are benign, with most being vestibular schwannomas. Meningiomas arising from the jugular foramen are among the rarest of all with very few being described in the literature. Treatment options vary considerably as experience with these tumours is limited. One option is a skull base approach, but this depends on size, location and ability to preserve lower cranial nerve function. This can be extremely challenging and is accompanied by high mortality risk; therefore, a more conservative option must be considered. This case report highlights the difficulty in management of patients with jugular fossa meningiomas, including appropriate investigations, analysis of surgical versus conservative treatment and associated complications. Furthermore, we elaborate the decision-making process pertaining to the tailoring of the surgical route used for the resection of jugular foramen meningiomas. (Jugular Foramen Meningioma, cerebellopontine angle). PMID:26486157

  20. Genetic/molecular alterations of meningiomas and the signaling pathways targeted

    PubMed Central

    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Ruiz, Laura; Miranda, David; Sousa, Pablo; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2015-01-01

    Meningiomas are usually considered to be benign central nervous system tumors; however, they show heterogenous clinical, histolopathological and cytogenetic features associated with a variable outcome. In recent years important advances have been achieved in the identification of the genetic/molecular alterations of meningiomas and the signaling pathways involved. Thus, monosomy 22, which is often associated with mutations of the NF2 gene, has emerged as the most frequent alteration of meningiomas; in addition, several other genes (e.g. AKT1, KLF4, TRAF7, SMO) and chromosomes have been found to be recurrently altered often in association with more complex karyotypes and involvement of multiple signaling pathways. Here we review the current knowledge about the most relevant genes involved and the signaling pathways targeted by such alterations. In addition, we summarize those proposals that have been made so far for classification and prognostic stratification of meningiomas based on their genetic/genomic features. PMID:25965831

  1. Meningiomas and Proteomics: Focus on New Potential Biomarkers and Molecular Pathways.

    PubMed

    Abbritti, Rosaria Viola; Polito, Francesca; Cucinotta, Maria; Lo Giudice, Claudio; Caffo, Maria; Tomasello, Chiara; Germanò, Antonino; Aguennouz, Mohammed

    Meningiomas are one of the most common tumors affecting the central nervous system, exhibiting a great heterogeneity in grading, treatment and molecular background. This article provides an overview of the current literature regarding the molecular aspect of meningiomas. Analysis of potential biomarkers in serum, cerebrospinal fluid (CSF) and pathological tissues was reported. Applying bioinformatic methods and matching the common proteic profile, arising from different biological samples, we highlighted the role of nine proteins, particularly related to tumorigenesis and grading of meningiomas: serpin peptidase inhibitor alpha 1, ceruloplasmin, hemopexin, albumin, C3, apolipoprotein, haptoglobin, amyloid-P-component serum and alpha-1-beta-glycoprotein. These proteins and their associated pathways, including complement and coagulation cascades, plasma lipoprotein particle remodeling and lipid metabolism could be considered possible diagnostic, prognostic biomarkers, and eventually therapeutic targets. Further investigations are needed to better characterize the role of these proteins and pathways in meningiomas. The role of new therapeutic strategies are also discussed. PMID:27566655

  2. Benign Sphenoid Wing Meningioma Presenting with an Acute Intracerebral Hemorrhage – A Case Report

    PubMed Central

    Frič, Radek; Hald, John K.; Antal, Ellen-Ann

    2016-01-01

    BACKGROUND AND STUDY OBJECT We report an unusual case of a benign lateral sphenoid wing meningioma that presented with, and was masked by, an acute intracerebral hemorrhage. CASE REPORT A 68-year-old woman was admitted after sudden onset of coma. Computed tomography (CT) revealed an intracerebral hemorrhage, without any underlying vascular pathology on CT angiography. During the surgery, we found a lateral sphenoid wing meningioma with intratumoral bleeding that extended into the surrounding brain parenchyma. RESULTS We removed the hematoma and resected the tumor completely in the same session. The histopathological classification of the tumor was a WHO grade I meningothelial meningioma. The patient recovered very well after surgery, without significant neurological sequelae. CONCLUSIONS: Having reviewed the relevant references from the medical literature, we consider this event as an extremely rare presentation of a benign sphenoid wing meningioma in a patient without any predisposing medical factors. The possible mechanisms of bleeding from this tumor type are discussed. PMID:27127413

  3. Hormone-dependent shrinkage of a sphenoid wing meningioma after pregnancy: case report.

    PubMed

    Kerschbaumer, Johannes; Freyschlag, Christian F; Stockhammer, Günter; Taucher, Susanne; Maier, Hans; Thomé, Claudius; Seiz-Rosenhagen, Marcel

    2016-01-01

    Meningiomas are known to be associated with female sex hormones. Worsening neurological symptoms or newly diagnosed meningiomas have been described in the context of elevated levels of sex hormones, for example, in pregnancy. To the authors' knowledge, tumor shrinkage after the normalization of hormones has not been described, even if it is known that neurological deficits due to meningioma compression may improve after giving birth. A 32-year-old female patient presented with severe headache and vision disturbances at the end of her second pregnancy. Magnetic resonance imaging revealed an extended mass at the lateral left-sided sphenoid wing that was suspected to be a meningioma. After delivery, the patient's symptoms improved, and MRI obtained 2 months postpartum showed significant shrinkage of the lesion. Significant tumor shrinkage can occur after pregnancy. Thus, repeat imaging is indicated in these patients. PMID:26162042

  4. Meningioma: The role of a foreign body and irradiation in tumor formation

    SciTech Connect

    Saleh, J.; Silberstein, H.J.; Salner, A.L.; Uphoff, D.F. )

    1991-07-01

    A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented. 47 references.

  5. Regression of Intracranial Meningioma during Treatment with α1-Adrenoceptor Blocker.

    PubMed

    Hoegestoel, Einar August; Berg-Johnsen, Jon

    2016-03-01

    Background Regression of meningioma has been reported after hemorrhage or hormonal withdrawal. Here, we report a case of an incidentally diagnosed meningioma that regressed in association with α1-adrenoceptor antagonist. Case report A 59-year old male patient with an incidentally diagnosed lateral sphenoid wing meningioma was followed with serial magnetic resonance imaging. The tumor with a maximum diameter of 43 mm showed progressive regression, and after 3 years the size was reduced to 22% of the initial volume. During follow-up the patient was treated with an α1-adrenoceptor antagonist (tamsulosin) for benign prostatic hyperplasia. Possible mechanisms are discussed, including our main hypothesis of reduced mitogenic effects through phospholipase C-signal transduction. Conclusion This is the first report of regression of an incidentally diagnosed meningioma associated with α1-adrenoceptor antagonist treatment. PMID:27175325

  6. Unilateral proptosis and blindness caused by meningioma in a patient treated with cyproterone acetate

    PubMed Central

    Sys, Celine; Kestelyn, Philippe

    2015-01-01

    Cyproterone has antiandrogenic, antigonadotropic, and progestagenic activity. High-dose preparations are used for treatment of prostate cancer and for treatment of hypersexuality. We describe a patient who was referred to our clinic with slowly progressive unilateral proptosis and blindness of the left eye. He had been treated with high-dose cyproterone actate (CPA) for 23 years. An obvious proptosis and exodeviation of his left eye was noted on ophthalmic examination. Fundoscopy showed left optic atrophy. The literature suggests a link between long-term high-dose exogenous progesterone agonist exposure and the progression and/or development of meningioma. MRI of the brain was performed and revealed multiple meningiomas. One large meningioma located in the anterior temporal lobe extended into the left orbit and caused the proptosis and blindness. Treatment with CPA was stopped and follow-up imaging 11 months later showed a significant decrease in size of the largest meningiomas.

  7. Radiation-induced cerebellar chondrosarcoma. Case report

    SciTech Connect

    Bernstein, M.; Perrin, R.G.; Platts, M.E.; Simpson, W.J.

    1984-07-01

    The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation.

  8. Improving cerebellar segmentation with statistical fusion

    NASA Astrophysics Data System (ADS)

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-03-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multiatlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non- Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

  9. Improving Cerebellar Segmentation with Statistical Fusion

    PubMed Central

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-01-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multi-atlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non-Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution. PMID:27127334

  10. Inverse Stochastic Resonance in Cerebellar Purkinje Cells

    PubMed Central

    Häusser, Michael; Gutkin, Boris S.; Roth, Arnd

    2016-01-01

    Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

  11. Cerebellar Disease in an Adult Cow

    PubMed Central

    Oz, H. H.; Nicholson, S. S.; Al-Bagdadi, F. K.; Zeman, D. H.

    1986-01-01

    This is the report of clinical signs and lesions of a cerebellar disorder in an adult four year old Limousin cow grazing perennial ryegrass (Lolium perenne). The most striking histopathological lesion was a marked paucity of Purkinje cells throughout the cerebellum. ImagesFigure 1.Figure 2. PMID:17422607

  12. Inverse Stochastic Resonance in Cerebellar Purkinje Cells.

    PubMed

    Buchin, Anatoly; Rieubland, Sarah; Häusser, Michael; Gutkin, Boris S; Roth, Arnd

    2016-08-01

    Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

  13. A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.

    PubMed

    Li, Chiao-Zhu; Li, Chiao-Ching; Lin, Meng-Chi; Chih-Chuan, Hsieh; Chen, Nan-Fu; Chen, Chun-Lin; Tang, Chi-Tun

    2015-11-01

    Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma. PMID:26566041

  14. Differential Diagnosis of Meningeal SFT-HPC and Meningioma: Which Immunohistochemical Markers Should Be Used?

    PubMed

    Macagno, Nicolas; Figarella-Branger, Dominique; Mokthari, Karima; Metellus, Philippe; Jouvet, Anne; Vasiljevic, Alexandre; Loundou, Anderson; Bouvier, Corinne

    2016-02-01

    Meningeal solitary fibrous tumors-hemangiopericytomas (SFT-HPC) and meningiomas can be difficult to distinguish on histologic examination. STAT6 immunohistochemistry (IHC) is a reliable diagnostic marker of SFT-HPCs. Recently, GRIA2 has also been reported to be a diagnostic marker of SFT-HPC, although no extensive data are available for meningeal SFT-HPCs yet. The aim of this study was to test their diagnostic performance in a large cohort of SFT-HPCs and meningiomas. IHC analyses for GRIA2 and STAT6 were performed on tissue microarrays containing 76 SFT-HPCs and 181 meningiomas. Results were compared with previous data with ALDH1 and CD34. Two different anti-STAT6 antibodies were tested: SC-20 polyclonal and YE361 monoclonal antibody. Ninety-six percent of meningeal SFT-HPCs but no meningioma displayed nuclear STAT6 positivity. With SC-20 antibody, concomitant cytoplasmic staining for STAT6 was observed in >50% of all cases, including meningiomas. However, using YE361 antibody, cytoplasmic staining was absent, and nuclear signal intensity was stronger leading to better interpretation of STAT6 IHC. GRIA2 was positive in 84% of SFT-HPCs and in 16% of meningiomas. STAT6 had excellent sensitivity (96%) and specificity (100%), ALDH1 and GRIA2 had same sensitivity (84%), but ALDH1 and CD34 had better specificity than GRIA2 (97% and 96% vs. 84%, respectively). For the differential diagnosis of SFT-HPCs versus meningiomas, the best diagnostic approach is to perform STAT6, followed by ALDH1 and CD34 in the case of uncommon STAT6-negative cases. Because of meningioma positivity, GRIA2 seems less useful in this indication. PMID:26448189

  15. Triad of Intraspinal Meningioma, Schwannoma, and Ependymoma: Report of an Extremely Rare Case.

    PubMed

    Rasheed, Faiza; Fatima, Saira; Ahmad, Zubair

    2016-02-01

    Mixed tumors composed of schwannoma and meningioma are extremely rare and are usually associated with neurofibromatosis type 2. So far, all the cases reported have involved the cerebellopontine angle. Only 3 reported cases did not have a clear association with neurofibromatosis type 2. We report a mixed tumor comprising schwannoma admixed with meningioma and ependymoma in the cervical spinal cord of a 22-year-old male. PMID:26316051

  16. Expression of ZIC family genes in meningiomas and other brain tumors

    PubMed Central

    2010-01-01

    Background Zic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Although human ZIC genes are known to be molecular markers for medulloblastomas, their expression in meningioma has not been addressed to date. Methods We examined the mRNA and protein expression of human ZIC1, ZIC2, ZIC3, ZIC4 and ZIC5 genes in meningiomas in comparison to other brain tumors, using RT-PCR, analysis of published microarray data, and immunostaining. Results ZIC1, ZIC2 and ZIC5 transcript levels in meningiomas were higher than those in whole brain or normal dura mater, whereas all five ZIC genes were abundantly expressed in medulloblastomas. The expression level of ZIC1 in public microarray data was greater in meningiomas classified as World Health Organization Grade II (atypical) than those classified as Grade I (benign). Immunoscreening using anti-ZIC antibodies revealed that 23 out of 23 meningioma cases were ZIC1/2/3/5-immunopositive. By comparison, nuclear staining by the anti-ZIC4 antibody was not observed in any meningioma case, but was strongly detected in all four medulloblastomas. ZIC-positive meningiomas included meningothelial, fibrous, transitional, and psammomatous histological subtypes. In normal meninges, ZIC-like immunoreactivities were detected in vimentin-expressing arachnoid cells both in human and mouse. Conclusions ZIC1, ZIC2, and ZIC5 are novel molecular markers for meningiomas whereas ZIC4 expression is highly selective for medulloblastomas. The pattern of ZIC expression in both of these tumor types may reflect the properties of the tissues from which the tumors are derived. PMID:20199689

  17. MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma.

    PubMed

    Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

    2015-05-01

    MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan-Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan-Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. PMID:25783051

  18. Improved segmentation of cerebellar structures in children

    PubMed Central

    Narayanan, Priya Lakshmi; Boonazier, Natalie; Warton, Christopher; Molteno, Christopher D; Joseph, Jesuchristopher; Jacobson, Joseph L; Jacobson, Sandra W; Zöllei, Lilla; Meintjes, Ernesta M

    2016-01-01

    Background Consistent localization of cerebellar cortex in a standard coordinate system is important for functional studies and detection of anatomical alterations in studies of morphometry. To date, no pediatric cerebellar atlas is available. New method The probabilistic Cape Town Pediatric Cerebellar Atlas (CAPCA18) was constructed in the age-appropriate National Institute of Health Pediatric Database asymmetric template space using manual tracings of 16 cerebellar compartments in 18 healthy children (9–13 years) from Cape Town, South Africa. The individual atlases of the training subjects were also used to implement multi atlas label fusion using multi atlas majority voting (MAMV) and multi atlas generative model (MAGM) approaches. Segmentation accuracy in 14 test subjects was compared for each method to ‘gold standard’ manual tracings. Results Spatial overlap between manual tracings and CAPCA18 automated segmentation was 73% or higher for all lobules in both hemispheres, except VIIb and X. Automated segmentation using MAGM yielded the best segmentation accuracy over all lobules (mean Dice Similarity Coefficient 0.76; range 0.55–0.91). Comparison with existing methods In all lobules, spatial overlap of CAPCA18 segmentations with manual tracings was similar or higher than those obtained with SUIT (spatially unbiased infra-tentorial template), providing additional evidence of the benefits of an age appropriate atlas. MAGM segmentation accuracy was comparable to values reported recently by Park et al. (2014) in adults (across all lobules mean DSC = 0.73, range 0.40–0.89). Conclusions CAPCA18 and the associated multi atlases of the training subjects yield improved segmentation of cerebellar structures in children. PMID:26743973

  19. Orthostatic hypotension in acute cerebellar infarction.

    PubMed

    Kim, Hyun-Ah; Lee, Hyung

    2016-01-01

    To investigate the frequency and pattern of orthostatic hypotension (OH) associated with acute isolated cerebellar infarction, and to identify the cerebellar structure(s) potentially responsible for OH, 29 patients (mean age 60.0) with acute isolated cerebellar infarction performed a standard battery of autonomic function tests including the head up tilt test using Finapres for recording of the beat-to-beat BP response during the acute period. Cerebellar infarction related OH was defined as fall in BP (>20 mmHg systolic BP) on tilting in patients without any disease(s) that could potentially cause autonomic dysfunction, or in patients who had a potential cause of autonomic dysfunction, but showed the absence of OH during a follow-up test. The severity and distribution of autonomic dysfunction were measured by the composite autonomic severity score (CASS). Nine patients (31 %) had OH (range 24-53 mmHg) on tilting during the acute period. Most patients (7/9) had a remarkable decrement in systolic BP immediately upon tilting, but OH rapidly normalized. Mean of maximal decrease in systolic BP during head up tilt test was 37.0 mmHg. The OH group showed mild autonomic dysfunctions (CASS, 3.7) with adrenergic sympathetic dysfunction appearing as the most common abnormality. Lesion subtraction analyses revealed that damage to the medial part of the superior semilunar lobule (Crus I) and tonsil was more frequent in OH group compared to non-OH group. Cerebellar infarction may cause a brief episode of OH. The medial part of the superior semilunar lobule and tonsil may participate in regulating the early BP response during orthostasis. PMID:26530504

  20. Group I Paks as therapeutic targets in NF2-deficient meningioma

    PubMed Central

    Duron, Sergio G.; Campbell, David A.; Ong, Christy C.; Hoeflich, Klaus P.; Chang, Long-Sheng; Welling, D. Bradley; Yang, Zeng-jie; Chernoff, Jonathan

    2015-01-01

    Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of NF2 is found in 40–60% of sporadic meningiomas, but the molecular mechanisms underlying malignant changes of meningioma cells remain unclear. Because group I p21-activated kinases (Paks) bind to and are inhibited by the NF2-encoded protein Merlin, we assessed the signaling and anti-tumor effects of three group-I specific Pak inhibitors - Frax597, 716 and 1036 - in NF2−/− meningiomas in vitro and in an orthotopic mouse model. We found that these Pak inhibitors suppressed the proliferation and motility of both benign (Ben-Men1) and malignant (KT21-MG1) meningiomas cells. In addition, we found a strong reduction in phosphorylation of Mek and S6, and decreased cyclin D1 expression in both cell lines after treatment with Pak inhibitors. Using intracranial xenografts of luciferase-expressing KT21-MG1 cells, we found that treated mice showed significant tumor suppression for all three Pak inhibitors. Similar effects were observed in Ben-Men1 cells. Tumors dissected from treated animals exhibited an increase in apoptosis without notable change in proliferation. Collectively, these results suggest that Pak inhibitors might be useful agents in treating NF2-deficient meningiomas. PMID:25596744

  1. Spinal meningiomas in dogs: Description of 8 cases including a novel radiological and histopathological presentation

    PubMed Central

    José-López, Roberto; de la Fuente, Cristian; Pumarola, Martí; Añor, Sonia

    2013-01-01

    Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis. PMID:24155414

  2. Spinal meningiomas in dogs: description of 8 cases including a novel radiological and histopathological presentation.

    PubMed

    José-López, Roberto; de la Fuente, Cristian; Pumarola, Martí; Añor, Sonia

    2013-10-01

    Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis. PMID:24155414

  3. Glucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study

    SciTech Connect

    Di Chiro, G.; Hatazawa, J.; Katz, D.A.; Rizzoli, H.V.; De Michele, D.J.

    1987-08-01

    Seventeen patients with intracranial meningiomas were studied with positron emission tomography and fluorine-18-2-fluorodeoxyglucose (PET-FDG) to assess the glucose utilization of these tumors. Four meningiomas followed for 3-5 years after PET-FDG and surgery showed no evidence of recurrence. These tumors had significantly lower glucose utilization rates (1.9 mg/dl/min +/- 1.0) than 11 recurrent or regrowing meningiomas (4.5 mg/dl/min +/- 1.96). The glucose metabolic rates of meningiomas correlated with tumor growth, as estimated from changes in tumor size on repeated computed tomographic scans. Histopathologically, a syncytial (atypical) meningioma had the highest glucose utilization rate, followed by a papillary meningioma and an angioblastic meningioma. Individual transitional and syncytial (typical) meningiomas showed marked differences in glucose metabolism despite similar microscopic appearance. Glucose utilization rate appears to be at least as reliable as histologic classification and other proposed criteria for predicting the behavior and recurrence of intracranial meningiomas.

  4. Ponto-bulbar palsy with deafness (Brown-Vialetto-Van Laere syndrome).

    PubMed

    Gallai, V; Hockaday, J M; Hughes, J T; Lane, D J; Oppenheimer, D R; Rushworth, G

    1981-05-01

    The authors describe the clinical and electrophysiological features in 2 cases of ponto-bulbar palsy with deafness, and the clinical course and post-mortem findings in a sibling of one of these, who died in infancy, and who appears to have suffered from the same disease. The cases are compared with 17 previously published cases, and the disease is discussed in relation to other progressive neurological diseases of childhood. PMID:7229669

  5. Primary Intracranial Myoepithelial Neoplasm: A Potential Mimic of Meningioma.

    PubMed

    Choy, Bonnie; Pytel, Peter

    2016-05-01

    Myoepithelial neoplasms were originally described in the salivary glands but their spectrum has been expanding with reports in other locations, including soft tissue. Intracranial cases are exceptionally rare outside the sellar region where they are assumed to be arising from Rathke pouch rests. Two cases of pediatric intracranial myoepithelial neoplasm in the interhemispheric fissure and the right cerebral hemisphere are reported here. Imaging studies suggest that the second case was associated with cerebrospinal fluid dissemination. Both cases showed typical variation in morphology and immunophenotype between more epithelioid and more mesenchymal features. The differential diagnosis at this particular anatomic location includes meningioma, which can show some overlap in immunophenotype since both tumors express EMA as well as GLUT1. One case was positive for EWSR1 rearrangement by fluorescence in situ hybridization. One patient is disease free at last follow-up while the other succumbed to the disease within days illustrating the clinical spectrum of these tumors. PMID:26510861

  6. Optic Nerve Sheath Meningioma Masquerading as Optic Neuritis

    PubMed Central

    Alroughani, R.; Behbehani, R.

    2016-01-01

    Optic neuritis is a common presentation of demyelinating disorders such as multiple sclerosis. It typically presents with acute painful monocular vision loss, whereas chronic optic neuropathy can be caused by compressive lesions along the anterior visual pathway, genetic, toxic, or nutritional causes. We report an unusual presentation mimicking optic neuritis, which was subsequently diagnosed as optic nerve sheath meningioma (ONSM). Misinterpretation of white matter lesions on MRI of brain and the failure to image the optic nerves at the time of acute loss of vision led to the misdiagnosis of optic neuritis in this case. A comprehensive accurate history and ordering the appropriate imaging modality remain paramount in diagnosing progressive visual deterioration. PMID:26904329

  7. Meningioma as a cause of chronic orofacial pain: case reports.

    PubMed

    Cook, R J; Sharif, I; Escudier, M

    2008-09-01

    We describe two middle-aged men whose chronic orofacial pain was caused by underlying meningiomas. In both cases treatment was delayed because evolving dentoalveolar and possible chronic idiopathic facial pain had been investigated before presentation. Subsequent disturbances of the ipsilateral VII (and later VIII) nerves prompted magnetic resonance imaging (MRI) of one patient, while the possibility of a central lesion was recognised at presentation in the second, whose atypical focus of trigeminal neuralgia was labile within the ipsilateral distribution of the trigeminal nerve. Both cases highlight the importance of considering proximal intracranial lesions as a possible cause of atypical or refractory chronic orofacial pain so unnecessary delay in the diagnosis of otherwise operable tumours can be avoided. PMID:18304709

  8. Optic Nerve Sheath Meningioma Masquerading as Optic Neuritis.

    PubMed

    Alroughani, R; Behbehani, R

    2016-01-01

    Optic neuritis is a common presentation of demyelinating disorders such as multiple sclerosis. It typically presents with acute painful monocular vision loss, whereas chronic optic neuropathy can be caused by compressive lesions along the anterior visual pathway, genetic, toxic, or nutritional causes. We report an unusual presentation mimicking optic neuritis, which was subsequently diagnosed as optic nerve sheath meningioma (ONSM). Misinterpretation of white matter lesions on MRI of brain and the failure to image the optic nerves at the time of acute loss of vision led to the misdiagnosis of optic neuritis in this case. A comprehensive accurate history and ordering the appropriate imaging modality remain paramount in diagnosing progressive visual deterioration. PMID:26904329

  9. A carcinoid tumor mimicking an isolated intracranial meningioma. Case report.

    PubMed

    Deshaies, Eric M; Adamo, Matthew A; Qian, Jiang; DiRisio, Darryl A

    2004-11-01

    This 79-year-old woman presented with progressively worsening dementia, abulia, flat affect, urinary incontinence, and profuse watery diarrhea. Results of computerized tomography and magnetic resonance studies indicated an extraaxial, dural-based mass compressing the right frontal lobe and consistent with a convexity meningioma. A right frontal craniotomy was performed and the dural-based mass was resected. Histopathological features on immunostaining of the lesion were consistent with a carcinoid tumor (low-grade neuroendocrine carcinoma). Further evaluation revealed no primary carcinoid tumor in the foregut from which they typically originate. The authors concluded that this intracranial carcinoid tumor was the primary lesion despite its unusual location and that it should be included in the differential diagnosis of dural-based, extraaxial brain lesions. PMID:15540927

  10. Hypofractionated stereotactic radiation therapy in skull base meningiomas.

    PubMed

    Navarria, Pierina; Pessina, Federico; Cozzi, Luca; Clerici, Elena; Villa, Elisa; Ascolese, Anna Maria; De Rose, Fiorenza; Comito, Tiziana; Franzese, Ciro; D'Agostino, Giuseppe; Lobefalo, Francesca; Fogliata, Antonella; Reggiori, Giacomo; Fornari, Maurizio; Tomatis, Stefano; Bello, Lorenzo; Scorsetti, Marta

    2015-09-01

    To investigate the role of hypo-fractionated stereotactic radiation treatment (HSRT) in the management of skull base meningioma. Twenty-six patients were included in the study and treated with a dose of 30 Gy in 5 fractions with volumetric modulated arc therapy (RapidArc). Eighteen patients were symptomatic before treatment. Endpoints were local toxicity and relief from symptoms. Tumors were located in anterior skull base in 4/27 cases, in middle skull base in 12/27 and in posterior skull base in 11/27. HSRT was performed as first treatment in 17 (65 %) patients, in 9 (35 %) patients it followed a previous partial resection. Median follow up was 24.5 months (range 5-57 months). clinical remission of symptoms, complete or partial, was obtained in the vast majority of patients after treatment. Out of the 18 symptomatic patients, partial remission occurred in 9 (50 %) patients and complete remission in 9 (50 %). All asymptomatic patients retained their status after treatment. No severe neurologic toxicity grade III-IV was recorded. No increase of meningioma in the same site of treatment occurred; 16 (62 %) patients had stable disease and 9 (38 %) patients had tumor reduction. The mean tumor volume after treatment was 10.8 ± 17.8 cm(3) compared with 13.0 ± 19.1 cm(3) before treatment (p = 0.02). The mean actuarial OS was 54.4 ± 2.8 months. The 1- and 2-years OS was 92.9 ± 0.7 %. HSRT proved to be feasible for these patients not eligible to full surgery or to ablative radiation therapy. Local control and durability of results suggest for a routine application of this approach in properly selected cases. PMID:26040487

  11. Anatomy and approaches along the cerebellar-brainstem fissures.

    PubMed

    Matsushima, Ken; Yagmurlu, Kaan; Kohno, Michihiro; Rhoton, Albert L

    2016-01-01

    OBJECT Fissure dissection is routinely used in the supratentorial region to access deeply situated pathology while minimizing division of neural tissue. Use of fissure dissection is also practical in the posterior fossa. In this study, the microsurgical anatomy of the 3 cerebellar-brainstem fissures (cerebellomesencephalic, cerebellopontine, and cerebellomedullary) and the various procedures exposing these fissures in brainstem surgery were examined. METHODS Seven cadaveric heads were examined with a microsurgical technique and 3 with fiber dissection to clarify the anatomy of the cerebellar-brainstem and adjacent cerebellar fissures, in which the major vessels and neural structures are located. Several approaches directed along the cerebellar surfaces and fissures, including the supracerebellar infratentorial, occipital transtentorial, retrosigmoid, and midline suboccipital approaches, were examined. The 3 heads examined using fiber dissection defined the anatomy of the cerebellar peduncles coursing in the depths of these fissures. RESULTS Dissections directed along the cerebellar-brainstem and cerebellar fissures provided access to the posterior and posterolateral midbrain and upper pons, lateral pons, floor and lateral wall of the fourth ventricle, and dorsal and lateral medulla. CONCLUSIONS Opening the cerebellar-brainstem and adjacent cerebellar fissures provided access to the brainstem surface hidden by the cerebellum, while minimizing division of neural tissue. Most of the major cerebellar arteries, veins, and vital neural structures are located in or near these fissures and can be accessed through them. PMID:26274986

  12. Correlation of leptin receptor expression with BMI in differential grades of human meningiomas

    PubMed Central

    RUTKOWSKI, ROBERT; RESZEC, JOANNA; HERMANOWICZ, ADAM; CHRZANOWSKI, ROBERT; LYSON, TOMASZ; MARIAK, ZENON; CHYCZEWSKI, LECH

    2016-01-01

    Meningioma is one of the most common primary brain tumor, especially in postmenopausal women. The most important risk factors include radiation, primary head injury or genetic alterations, however it is currently unclear why postmenopausal women are predominantly affected. The aim of the present study was to evaluate leptin receptor (LEPR) expression and body mass index (BMI) in patients with meningiomas of differential grades. Specimens of 158 meningiomas were classified as either G1 (low-grade meningiomas, n=114) or G2/G3 (high-grade meningiomas, n=44). Immunohistochemistry was performed to assess LEPR expression. The mean BMIs of the female and male patient groups were 28.43±5.29 and 23.93±4.66, respectively. Mean BMI was significantly higher in the female group, by ~4.50 kg/m2. Patient age significantly correlated with LEPR expression, with the highly positive (++) and positive (+) groups having mean ages of 62.3±12.07 and 52.3±13.04, respectively. A strong positive correlation (r=0.73) was observed between leptin receptor expression and BMI, with the LEPR (++) group having a mean BMI of 30.11±4.49, compared to 22.12±2.48 for the LEPR (+) group. Furthermore, in the low-grade meningioma group, mean BMI was higher in female patients than male patients (28.13±5.54 and 25.38±4.57, respectively; P=0.01). Additionally, there was strong positive correlation between BMI and leptin receptor expression in the low-grade meningioma group (r=0.69). For the high-grade meningioma group, mean BMI was 29.49±4.26 and 21.76±3.98 in female and male patients, respectively, and LEPR expression strongly correlated with BMI in this group (r=0.80). The present study demonstrates a correlation between patient BMI, age, and LEPR expression status in low- and high-grade meningiomas. Our results indicate that in addition to endogenous hormones, such as estrogen or progesterone, or fatty tissue-associated proinflammatory cytokines, LEPR expression status may be a risk factor for

  13. Crossed Cerebellar Diaschisis: Three Case Reports Imaging Using a Tri-Modality PET/CT-MR System.

    PubMed

    Han, Shuguang; Wang, Xiaopeng; Xu, Kai; Hu, Chunfeng

    2016-01-01

    Crossed cerebellar diaschisis (CCD) describes a depression of oxidative metabolism glucose and blood flow in the cerebellum secondary to a supratentorial lesion in the contralateral cerebral hemisphere. PET/MR has the potential to become a powerful tool for demonstrating and imaging intracranial lesions .We herein report 3 cases of CCD imaging using a tri-modality PET/CT-MR set-up for investigating the value of adding MRI rather than CT to PET in clinical routine.We describe 3 patients with CCD and neurological symptoms in conjunction with abnormal cerebral fluorodeoxyglucose (FDG) positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT-MR) manifestations including arterial spin-labeling (ASL) and T2-weighted images. In all, 18FDG-PET/CT detected positive FDG uptake in supratentorial lesions, and hypometabolism with atrophy in the contralateral cerebellum. More than that, hybrid PET/MRI provided a more accurate anatomic localization and ASL indicated disruption of the cortico-ponto-cerebellar pathway.Using pathology or long-term clinical follow-up to confirm the PET and ASL findings, the supratentorial lesions of the 3 patients were respectively diagnosed with cerebral infarction, recurrent glioma, and metastasis.The reports emphasize the significance of multimodality radiological examinations. Multimodality imaging contributes to proper diagnosis, management, and follow-up of supratentorial lesions with CCD. PMID:26765477

  14. Cerebellar ataxia as presenting feature of hypothyroidism.

    PubMed

    Kotwal, Suman Kumar; Kotwal, Shalija; Gupta, Rohan; Singh, Jang Bhadur; Mahajan, Annil

    2016-04-01

    Symptoms and signs of the hypothyroidism vary in relation to the magnitude and acuteness of the thyroid hormone deficiency. The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Hypothyroidism should be suspected in all cases of ataxia, as it is easily treatable. A 40 year-old male presented with the history facial puffiness, hoarseness of voice and gait-ataxia. Investigations revealed frank primary hypothyroidism. Anti-TPO antibody was positive. Thyroxine was started and patient improved completely within eight weeks. Hypothyroidism can present with ataxia as presenting feature. Hypothyroidism should be considered in all cases of cerebellar ataxia as it is a reversible cause of ataxia. PMID:26886095

  15. An update on Spino-cerebellar ataxias

    PubMed Central

    Mondal, Banashree; Paul, Pritikanta; Paul, Madhuparna; Kumar, Hrishikesh

    2013-01-01

    The dominantly inherited ataxias, also known as Spino-cerebellar ataxias (SCAs), are rapidly expanding entities. New mutations are being identified at remarkable regularity. Recent awareness of molecular abnormalities in SCAs has addressed some of the long sought questions, but gaps in knowledge still exist. Three major categories of SCAs, according to molecular mechanisms, have evolved over recent few years: Polyglutamate expansion ataxia, non-coding zone repeat ataxia, and ataxia due to conventional mutation. Using the fulcrum of these mechanisms, the article provides an update of SCAs. Shared and specific clinical features, genetic abnormalities, and possible links between molecular abnormalities and cerebellar degeneration have been discussed. Emphasis has been placed on the mechanisms of polyglutamate toxicity. PMID:24101804

  16. Identification of a third protein 4.1 tumor suppressor, protein 4.1R, in meningioma pathogenesis

    SciTech Connect

    Robb, Victoria A.; Li, Wen; Gascard, Philippe; Perry, Arie; Mohandas, Narla; Gutmann, David H.

    2003-06-11

    Meningiomas are common tumors of the central nervous system, however, the mechanisms under lying their pathogenesis are largely undefined. Two members of the Protein 4.1 super family, the neuro fibromatosis 2 (NF2) gene product (merlin/schwannomin) and Protein 4.1B have been implicated as meningioma tumor suppressors. In this report, we demonstrate that another Protein 4.1 family member, Protein 4.1R, also functions as a meningioma tumor suppressor. Based on the assignment of the Protein 4.1R gene to chromosome 1p32-36, a common region of deletion observed in meningiomas, we analyzed Protein 4.1R expression in meningioma cell lines and surgical tumor specimens. We observed loss of Protein 4.1R protein expression in two meningioma cell lines (IOMM-Lee, CH157-MN) by Western blotting as well as in 6 of 15 sporadic meningioma as by immuno histo chemistry (IHC). Analysis of a subset of these sporadic meningiomas by fluorescent in situ hybridization (FISH) with a Protein 4.1R specific probe demonstrated 100 percent concordance with the IHC results. In support of a meningioma tumor suppressor function, over expression of Protein 4.1R resulted in suppression of IOMM-Lee and CH157MN cell proliferation. Similar to the Protein 4.1B and merlin meningioma tumor suppressors, Protein 4.1R localization in the membrane fraction increased significantly under conditions of growth arrest in vitro. Lastly, Protein 4.1R interacted with some known merlin/Protein 4.1B interactors such as CD44 and bII-spectrin, but did not associate with the Protein 4.1B interactors 14-3-3 and PRMT3 or the merlin binding proteins SCHIP-1 and HRS. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor important in the molecular pathogenesis of meningioma.

  17. Possible interaction between ionizing radiation, smoking, and gender in the causation of meningioma.

    PubMed

    Flint-Richter, Pazit; Mandelzweig, Lori; Oberman, Bernice; Sadetzki, Siegal

    2011-03-01

    Data on the association between smoking and meningioma are inconsistent. The aim of this study was to assess the role of smoking in radiation- and non-radiation-related meningiomas. The study was designed as a 4-group case-control study, balanced for irradiation, including 160 irradiated meningioma case patients, 145 irradiated control subjects, 82 nonirradiated case patients, and 135 nonirradiated control subjects. The sources of these groups included a cohort of individuals who underwent radiotherapy (mean dose, 1.5 Gy to the brain) during childhood for treatment of tinea capitis, claims filed for radiation damage in the framework of a compensation law, and the Israel Cancer Registry. All tests of statistical significance were 2-sided. A statistically significantly elevated risk of meningioma was found among men who had ever smoked, compared with those who were never smokers (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.09-4.15), increasing with smoking pack-years from 1.67 to 2.69 for <10 to >20 pack-years, respectively. Among women, an interaction between radiation and smoking was observed, expressed by a significant protective effect for meningioma (OR, 0.32; 95% CI, 0.14-0.77), with a strong dose-response association (P < .01) in non-irradiated women and a nonsignificant increased risk of meningioma among those who were irradiated (OR, 1.23; 95% CI, 0.68-2.23). Variation in the association between smoking and meningioma may be explained by effects of distinct host factors, such as past exposure to ionizing radiation and/or hormonal factors. PMID:21339193

  18. Visual Outcome in Meningiomas Around Anterior Visual Pathways Treated With Linear Accelerator Fractionated Stereotactic Radiotherapy

    SciTech Connect

    Stiebel-Kalish, Hadas; Reich, Ehud; Gal, Lior; Rappaport, Zvi Harry; Nissim, Ouzi; Pfeffer, Raphael; Spiegelmann, Roberto

    2012-02-01

    Purpose: Meningiomas threatening the anterior visual pathways (AVPs) and not amenable for surgery are currently treated with multisession stereotactic radiotherapy. Stereotactic radiotherapy is available with a number of devices. The most ubiquitous include the gamma knife, CyberKnife, tomotherapy, and isocentric linear accelerator systems. The purpose of our study was to describe a case series of AVP meningiomas treated with linear accelerator fractionated stereotactic radiotherapy (FSRT) using the multiple, noncoplanar, dynamic conformal rotation paradigm and to compare the success and complication rates with those reported for other techniques. Patients and Methods: We included all patients with AVP meningiomas followed up at our neuro-ophthalmology unit for a minimum of 12 months after FSRT. We compared the details of the neuro-ophthalmologic examinations and tumor size before and after FSRT and at the end of follow-up. Results: Of 87 patients with AVP meningiomas, 17 had been referred for FSRT. Of the 17 patients, 16 completed >12 months of follow-up (mean 39). Of the 16 patients, 11 had undergone surgery before FSRT and 5 had undergone FSRT as first-line management. Tumor control was achieved in 14 of the 16 patients, with three meningiomas shrinking in size after RT. Two meningiomas progressed, one in an area that was outside the radiation field. The visual function had improved in 6 or stabilized in 8 of the 16 patients (88%) and worsened in 2 (12%). Conclusions: Linear accelerator fractionated RT using the multiple noncoplanar dynamic rotation conformal paradigm can be offered to patients with meningiomas that threaten the anterior visual pathways as an adjunct to surgery or as first-line treatment, with results comparable to those reported for other stereotactic RT techniques.

  19. Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression

    PubMed Central

    Schulten, Hans-Juergen; Hussein, Deema; Al-Adwani, Fatima; Karim, Sajjad; Al-Maghrabi, Jaudah; Al-Sharif, Mona; Jamal, Awatif; Al-Ghamdi, Fahad; Baeesa, Saleh S.; Bangash, Mohammed; Chaudhary, Adeel; Al-Qahtani, Mohammed

    2016-01-01

    Meningiomas are the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although meningiomas are stratified according to their histology and clinical behavior, the underlying molecular genetics predicting aggressiveness are not thoroughly understood. We performed whole transcript expression profiling in 10 grade I and four grade II meningiomas, three of which invaded the brain. Microarray expression analysis identified deleted in colorectal cancer (DCC) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into DCC low expression (3 grade I and 3 grade II tumors), DCC medium expression (2 grade I and 1 grade II tumors), and DCC high expression (5 grade I tumors) groups. Comparison between the DCC low expression and DCC high expression groups resulted in 416 DEGs (p-value < 0.05; fold change > 2). The most significantly downregulated genes in the DCC low expression group comprised DCC, phosphodiesterase 1C (PDE1C), calmodulin-dependent 70kDa olfactomedin 2 (OLFM2), glutathione S-transferase mu 5 (GSTM5), phosphotyrosine interaction domain containing 1 (PID1), sema domain, transmembrane domain (TM) and cytoplasmic domain, (semaphorin) 6D (SEMA6D), and indolethylamine N-methyltransferase (INMT). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (C5orf63), homeodomain interacting protein kinase 2 (HIPK2), and basic helix-loop-helix family, member e40 (BHLHE40). Biofunctional analysis identified as predicted top upstream regulators beta-estradiol, TGFB1, Tgf beta complex, LY294002, and dexamethasone and as predicted top regulator effectors NFkB, PIK3R1, and CREBBP. The microarray expression data served also for a comparison between meningiomas from female and male patients and for a comparison between brain invasive and non-invasive meningiomas resulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, DCC may constitute

  20. Combined treatment by octreotide and everolimus: Octreotide enhances inhibitory effect of everolimus in aggressive meningiomas.

    PubMed

    Graillon, Thomas; Defilles, Céline; Mohamed, Amira; Lisbonis, Christophe; Germanetti, Anne-Laure; Chinot, Olivier; Figarella-Branger, Dominique; Roche, Pierre-Hugues; Adetchessi, Tarek; Fuentes, Stéphane; Metellus, Philippe; Dufour, Henry; Enjalbert, Alain; Barlier, Anne

    2015-08-01

    Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas. To investigate new therapeutic strategies, we evaluated the activity of everolimus (mTOR inhibitor), BKM-120 and BEZ-235 (new Pi3K/Akt/mTOR inhibitors), octreotide and a combined treatment (octreotide plus everolimus), on cell proliferation, signaling pathways, and cell cycle proteins, respectively. The in vitro study was conducted on human meningioma primary cells extracted from fresh tumors, allowing the assessment of somatostatin analogs at the concentration levels used in patients. The results were correlated to WHO grades. Further, everolimus decreased cell viability of human meningiomas, but concomitantly, induced Akt activation, reducing the antiproliferative effect of the drug. The new Pi3K inhibitors were not more active than everolimus alone, limiting their clinical relevance. In contrast, a clear cooperative inhibitory effect of octreotide and everolimus was observed on cell proliferation in all tested meningiomas, including WHO grades II-III. Octreotide not only reversed everolimus-induced Akt phosphorylation but also displayed additive and complementary effects with everolimus on downstream proteins involved in translation (4EB-P1), and controlling cell cycle (p27Kip1 and cyclin D1). We have demonstrated a co-operative action between everolimus and octreotide on cell proliferation in human meningiomas, including aggressive ones, establishing the basis for a clinical trial. PMID:26015296

  1. [Diagnostic and treatment of hypertensive cerebellar hematomas].

    PubMed

    Krylov, V V; Dash'ian, V G; Murashko, A A; Burov, S A

    2009-01-01

    Authors analyzed the results of treatment of 56 patients with hypertensive cerebellar hemorrhages (volume 0,5-41 cm3). Brain stem symptoms were found in 45 (80%) of patients. The dislocation of brain stem was observed in 38 (68%) cases, occlusive hydrocephaly - in 22 (39%), intraventricular hemorrhage - in 26 (46%). Severity of state depended on character of disease course, presence of stem symptoms, awakening level, volume and localization of cerebellar hematoma, development of intraventricular hemorrhage, occlusive hydrocephaly and dislocation of brain stem. Thirty-six patients were operated. After the neurosurgical intervention, 22 (61%) patients were discharged without or with the minimal neurological deficit, 1 (3%) with marked disability and 13 (36%) patients died. In conclusion, the removal of hematoma is recommended in dislocation of brain stem and disturbance of consiousnes: the ventricular drainage - in occlusive hydrocephaly developed as a consequence of hemotamponade of IV ventricular. The surgical treatment is not recommended to patients with cerebellar hematomas with the volume less than 7 cm3. PMID:19491806

  2. Learning of Sensory Sequences in Cerebellar Patients

    PubMed Central

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for age, sex, handedness, musicality, and level of education were tested. Auditory and visual sensory sequences were presented out of different sensory pattern categories (tones with different acoustic frequencies and durations, visual stimuli with different spatial locations and colors, sequential vision of irregular shapes) and different ranges of inter-cue time intervals (fast and slow). Motor requirements were small, with vocal responses and no time restrictions. Perception of visual and acoustic stimuli was generally preserved in patients and controls. The number of errors was significantly higher in the faster tempo of sequence presentation in learning of sequences of tones of different frequencies and in learning of sequences of visual stimuli of different spatial locations and different colors. No difference in tempo between the groups was shown. The total number of errors between the two groups was identical in the sequence conditions. No major disturbances in acquisition or discrimination of various sensory sequences were observed in the group of cerebellar patients. Sequence learning may be impaired only in tasks with significant motor demands. PMID:15169865

  3. From cerebellar texture to movement optimization.

    PubMed

    Sultan, Fahad

    2014-10-01

    The cerebellum is a major site for supervised procedural learning and appears to be crucial for optimizing sensorimotor performance. However, the site and origin of the supervising signal are still elusive. Furthermore, its relationship with the prominent neuronal circuitry remains puzzling. In this paper, I will review the relevant information and seek to synthesize a working hypothesis that explains the unique cerebellar structure. The aim of this review was to link the distinctive functions of the cerebellum, as derived from cerebellar lesion studies, with potential elementary computations, as observed by a bottom-up approach from the cerebellar microcircuitry. The parallel fiber geometry is ideal for performing millisecond computations that extract instructive signals. In this scenario, the higher time derivatives of kinematics such as acceleration and/or jerk that occur during motor performance are detected via a tidal wave mechanism and are used (with appropriate gating) as the instructive signal to guide motor smoothing. The advantage of such a mechanism is that movements are optimized by reducing "jerkiness" which, in turn, lowers their energy requirements. PMID:25037239

  4. Cavernous angioma with olivary hypertrophy and contralateral cerebellar diaschisis.

    PubMed

    Komaba, Y; Nomoto, T; Kitamura, S; Terashi, A

    1997-07-01

    We describe a 66-year-old man with a 20-year history of ataxic gait who suddenly developed diplopia on rightward gaze. Neurologic examination revealed right hemi-ataxia and hemi-hypesthesia, and left internuclear ophthalmoplegia. MRI showed a cavernous angioma in the left tectum, mild right cerebellar atrophy, and left interior olivary hypertrophy. Single photon emission computed tomography (SPECT) imaging demonstrated contralateral cerebellar diaschisis. We discuss the findings and review the literature concerning contralateral cerebellar diaschisis. PMID:9240502

  5. Cerebro-cerebellar circuits in autism spectrum disorder

    PubMed Central

    D'Mello, Anila M.; Stoodley, Catherine J.

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD. PMID:26594140

  6. Cerebellar liponeurocytoma in two siblings suggests a possible familial predisposition.

    PubMed

    Pikis, Stylianos; Fellig, Yakov; Margolin, Emil

    2016-10-01

    There is limited data on the genetic origin and natural history of cerebellar liponeurocytoma. To the best of our knowledge there has been only one report of a familial presentation of this rare entity. We report a 72-year-old female with a posterior fossa tumor presenting with progressive cerebellar signs and symptoms. The patient underwent total tumor resection via an uncomplicated sub-occipital craniotomy. Histopathologic examination was diagnostic for cerebellar liponeurocytoma. Her sister was previously treated for a similar tumor. Our report provides further evidence for the possible existence of a hereditary abnormality predisposing afflicted families to cerebellar liponeurocytoma development. PMID:27349466

  7. Outcome of Elderly Patients with Meningioma after Image-Guided Stereotactic Radiotherapy: A Study of 100 Cases

    PubMed Central

    Budach, Volker; Graaf, Lukas; Gollrad, Johannes; Badakhshi, Harun

    2015-01-01

    Introduction. Incidence of meningioma increases with age. Surgery has been the mainstay treatment. Elderly patients, however, are at risk of severe morbidity. Therefore, we conducted this study to analyze long-term outcomes of linac-based fractionated stereotactic radiotherapy (FSRT) for older adults (aged ≥65 years) with meningioma and determine prognostic factors. Materials and Methods. Between October 1998 and March 2009, 100 patients (≥65, median age, 71 years) were treated with FSRT for meningioma. Two patients were lost to follow-up. Eight patients each had grade I and grade II meningiomas, and five patients had grade III meningiomas. The histology was unknown in 77 cases (grade 0). Results. The median follow-up was 37 months, and 3-year, 5-year, and 10-year progression-free survival (PFS) rates were 93.7%, 91.1%, and 82%. Patients with grade 0/I meningioma showed 3- and 5-year PFS rates of 98.4% and 95.6%. Patients with grade II or III meningiomas showed 3-year PFS rates of 36%. 93.8% of patients showed local tumor control. Multivariate analysis did not indicate any significant prognostic factors. Conclusion. FSRT may play an important role as a noninvasive and safe method in the clinical management of older patients with meningioma. PMID:26101778

  8. Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene

    PubMed Central

    Garaci, Francesco; Marsili, Luisa; Riant, Florence; Marziali, Simone; Cécillon, Michaelle; Pasquarelli, Roberto; Sangiuolo, Federica; Floris, Roberto; Novelli, Giuseppe; Tournier-Lasserve, Elisabeth

    2015-01-01

    Multiple familial meningiomas occur in rare genetic syndromes, particularly neurofibromatosis type 2. The association of meningiomas and cerebral cavernous malformations (CCMs) has been reported in few patients in the medical literature. The purpose of our study is to corroborate a preferential association of CCMs and multiple meningiomas in subjects harbouring mutations in the PDCD10 gene (also known as CCM3). Three members of an Italian family affected by seizures underwent conventional brain Magnetic Resonance Imaging (MRI) with gadolinium contrast agent including gradient echo (GRE) imaging. The three CCM-causative genes were sequenced by Sanger method. Literature data reporting patients with coexistence of CCMs and meningiomas were reviewed. MRI demonstrated dural-based meningioma-like lesions associated to multiple parenchymal CCMs in all affected individuals. A disease-causative mutation in the PDCD10 gene (p.Gln112PhefsX13) was identified. Based on neuroradiological and molecular data as well as on literature review, we outline a consistent association between PDCD10 mutations and a syndrome of CCMs with multiple meningiomas. This condition should be considered in the differential diagnosis of multiple/familial meningioma syndromes. In case of multiple/familial meningioma the use of appropriate MRI technique may include GRE and/or susceptibility-weighted imaging (SWI) to rule out CCM. By contrast, proper post-gadolinium scans may aid defining dural lesions in CCM patients and are indicated in PDCD10-mutated individuals. PMID:26246098

  9. MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma

    SciTech Connect

    Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

    2015-05-01

    MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan–Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan–Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. - Highlights: • MiR-224 expression is correlates with prognosis in meningioma patients. • ERG2 is a novel downstream target of miR-224. • MiR-224 suppressed cell growth and enhanced apoptosis in IOMM-Lee and CH157 cells. • MiR-224 is an upstream regulator of the ERG2

  10. The cognitive and behavioral effects of meningioma lesions involving the ventromedial prefrontal cortex.

    PubMed

    Abel, Taylor J; Manzel, Kenneth; Bruss, Joel; Belfi, Amy M; Howard, Matthew A; Tranel, Daniel

    2016-06-01

    OBJECT Anterior skull base meningiomas are frequently associated with changes in personality and behavior. Although such meningiomas often damage the ventromedial prefrontal cortex (vmPFC), which is important for higher cognition, the cognitive and behavioral effects of these meningiomas remain poorly understood. Using detailed neuropsychological assessments in a large series of patients, this study examined the cognitive and behavioral effects of meningioma lesions involving the vmPFC. METHODS The authors reviewed neuropsychology and lesion mapping records of 70 patients who underwent resection of meningiomas. The patients were drawn from the Neurological Patient Registry at the University of Iowa. Patients were sorted into 2 groups: those with lesions involving the vmPFC and those with lesions that did not involve the vmPFC. Neuropsychological data pertaining to a comprehensive array of cognitive and behavioral domains were available preoperatively in 20 patients and postoperatively in all 70 patients. RESULTS No change occurred in basic cognitive functions (e.g., attention, perception, memory, construction and motor performance, language, or executive functions) from the preoperative to postoperative epochs for the vmPFC and non-vmPFC groups. There was a significant decline in the behavioral domain, specifically adaptive function, for both the vmPFC and non-vmPFC groups, and this decline was more pronounced for the vmPFC group. Additionally, postoperative data indicated that the vmPFC group had a specific deficit in value-based decision making, as evidenced by poor performance on the Iowa Gambling Task, compared with the non-vmPFC group. The vmPFC and non-vmPFC groups did not differ postoperatively on other cognitive measures, including intellect, memory, language, and perception. CONCLUSIONS Lesions of the vmPFC resulting from meningiomas are associated with specific deficits in adaptive function and value-based decision making. Meningioma patients showed a

  11. Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

    SciTech Connect

    Maclean, Jillian; Fersht, Naomi; Bremner, Fion; Stacey, Chris; Sivabalasingham, Suganya; Short, Susan

    2013-03-15

    Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.

  12. CD133-positive cells might be responsible for efficient proliferation of human meningioma cells.

    PubMed

    Tang, Hailiang; Gong, Ye; Mao, Ying; Xie, Qing; Zheng, Mingzhe; Wang, Daijun; Zhu, Hongda; Wang, Xuanchun; Chen, Hong; Chen, Xiancheng; Zhou, Liangfu

    2012-01-01

    Owing to lack of appropriate model systems, investigations of meningioma biology have come to a stop. In this study, we developed a comprehensive digestion method and defined a culture system. Using this method and system, primary meningioma cells in conditioned suspension medium and a hypoxic environment could be amplified in spheres and were passaged for more than ten generations. Meningioma sphere cells were positive for meningioma cell markers and negative for markers of neural cell types. Importantly, we found the cells expressed the stem cell marker, CD133, but not nestin. All of the tumor sphere cell populations showed a slower degree of cell proliferation than that of human glioma cells and fetal neural stem cells (NSCs). Further studies showed that the proliferative rate was positively correlated with CD133 expression. The higher the CD133 expression, the faster the cell proliferation. With the increase in cell generations, the cell proliferation rate gradually slowed down, and CD133 expression also decreased. Single CD133(+) cells rather than CD133(-) cells could form spheres. Thus, the results above indicated that those cells expressing CD133 in spheres might be stem-like cells, which may be responsible for efficient amplification of human meningioma cells. Decreased expression of CD133 may lead to the failure of long-term passaging. PMID:22754374

  13. Recurrence of Skull Base Meningiomas: The Role of Aggressive Removal in Surgical Treatment.

    PubMed

    da Silva, Carlos Eduardo; Peixoto de Freitas, Paulo Eduardo

    2016-06-01

    Objectives The recurrence of meningiomas is a crucial aspect that must be considered during the planning of treatment strategy. The Simpson grade classification is the most relevant surgical aspect to predict the recurrence of meningiomas. We report on a series of patients with recurrent skull base meningiomas who were treated with the goal of radical removal. Design A retrospective study. Setting Hospital Ernesto Dornelles, Porto Alegre, Brazil. Participants Patients with recurrent skull base meningiomas. Main Outcomes Measures The goal of obtaining aggressive resection (i.e., Simpson grades I and II). Results The average age was 54 years, the mean follow-up period was 52.1 months, and Simpson grades I and II were obtained in 82%. The overall mortality was 5.8%. Transient cranial nerve deficits occurred in 11.7%; the definitive morbidity was also 5.8%. A second recurrence occurred in 5.8%. Conclusions Radical removal of recurrent skull base meningiomas is achievable and should be considered an option with a good outcome and an acceptable morbidity. The common surgical finding that was responsible for recurrence in this study was incomplete removal during the first surgery. We recommend extensive dura and bone removal in the surgical treatment of such recurrent lesions. PMID:27175316

  14. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    SciTech Connect

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-08-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.

  15. Estrophilin immunoreactivity versus estrogen receptor binding activity in meningiomas: evidence for multiple estrogen binding sites

    SciTech Connect

    Lesch, K.P.; Schott, W.; Gross, S.

    1987-09-01

    The existence of estrogen receptors in human meningiomas has long been a controversial issue. This may be explained, in part, by apparent heterogeneity of estrogen binding sites in meningioma tissue. In this study, estrogen receptors were determined in 58 meningiomas with an enzyme immunoassay using monoclonal antibodies against human estrogen receptor protein (estrophilin) and with a sensitive radioligand binding assay using /sup 125/I-labeled estradiol (/sup 125/I-estradiol) as radioligand. Low levels of estrophilin immunoreactivity were found in tumors from 62% of patients, whereas radioligand binding activity was demonstrated in about 46% of the meningiomas examined. In eight (14%) tissue samples multiple binding sites for estradiol were observed. The immunoreactive binding sites correspond to the classical, high affinity estrogen receptors: the Kd for /sup 125/I-estradiol binding to the receptor was approximately 0.2 nM and the binding was specific for estrogens. The second, low affinity class of binding sites considerably influenced measurement of the classical receptor even at low ligand concentrations. The epidemiological and clinical data from patients with meningiomas, and the existence of specific estrogen receptors confirmed by immunochemical detection, may be important factors in a theory of oncogenesis.

  16. [Cerebellar Control of Ocular Movements: Application to the Topographical Diagnosis of Cerebellar Lesions].

    PubMed

    Hirose, Genjiro

    2016-03-01

    Over the last decade, substantial information on cerebellar oculomotor control has been provided by the use of sophisticated neuroanatomical, neurophysiological, and imaging techniques. We now know that an intact cerebellum is a prerequisite for normal oculomotor performance. This review clarifies the current knowledge on structure-function correlations of the cerebellum in relation to ocular movements and allows them to be applied to topographical diagnosis of cerebellar lesions. The cerebellar regions most closely related to oculomotor function are: (1) the flocculus/paraflocculus for VOR suppression, cancellation, smooth pursuit eye movement and gaze-holding, (2) the nodulus/ventral uvula for velocity storage and low frequency prolonged vestibular response, and (3) the dorsal oculomotor vermis (declive VI, folium VII) and the posterior portion of the fastigial nucleus (fastigial oculomotor region) for saccades and smooth pursuit initiation. Symptomatically, defects in the flocculus/parflocculus cause saccadic pursuit, downbeat nystagmus, and impairments to visual suppression of the VOR. Lesions of the nodulus/uvula reveal as periodic alternating nystagmus. Lesions of the oculomotor vermis and the fastigial nucleus can induce saccadic dysmetria, while fastigial nucleus lesions may also cause ocular flutter/opsoclonus. A detailed knowledge of cerebellar anatomy and the physiology of eye movements enables localization of lesions to specific areas of the cerebellum. PMID:27001776

  17. Surgical implications of frontoethmoidal pneumosinus dilatans-associated proptosis caused by meningioma.

    PubMed

    Raheja, Amol; Abou Al-Shaar, Hussam; Patel, Bhupendra C; Couldwell, William T

    2016-08-01

    Pneumosinus dilatans (PSD) involves paranasal sinus enlargement without radiologic evidence of localized bone destruction, hyperostosis, or mucous membrane thickening. We discuss the surgical implications of PSD-associated proptosis in patients with anterior skull-base meningioma. A 20-year-old man with proptosis, hypoglobus, and lateral globe displacement had WHO grade I anterior skull-base and orbital meningiomas. Aggressive resection using anterior/medial orbitotomy and an anterior interhemispheric skull-base approach achieved Simpson grade I resection. Postoperatively, his symptoms improved, with no recurrence at 2-year follow-up. Although PSD-associated proptosis is relatively uncommon, it carries important clinical implications in surgical management of skull-base and orbital meningiomas. PMID:27246632

  18. [A case of multiple meningiomas: two lesions have different clinicopathological features, respectively].

    PubMed

    Oshita, Jumpei; Sogabe, Takashi; Maeda, Hitoshi; Sato, Hitoshi; Sugiyama, Kazuhiko; Kurisu, Kaoru

    2007-09-01

    A 60-year-old man presented with general convulsion. Computed tomographic (CT) scans and magnetic resonance (MR) imaging showed two meningiomas located at the bilateral frontal convex respectively. In spite of the similar tumor size, the left tumor only had marked peritumoral edema. Angiography showed that the left lesion was more amply supplied from the internal carotid artery than the right one was. These two tumors were totally resected. The left tumor adhered to the surrounding brain tissue more intensely than the right one. Both tumors were microscopically diagnosed as angiomatous meningioma. The left tumor cells have a stronger immunopositivity for VEGF than the right ones. We suggest that pial-blood supply, adhesion to brain tissue and VEGF expression influence the development of meningioma-associated peritumoral edema. PMID:17867314

  19. Electroconvulsive therapy in the presence of a metallic skull plate after meningioma resection.

    PubMed

    Ling, Ted; Manepalli, Jothika; Grossberg, George

    2010-06-01

    Electroconvulsive therapy (ECT) is an effective and safe treatment even in the frail and in the medically ill. A case report of ECT being administered to a patient with a history of a recently resected meningioma and the presence of a metallic skull plate is presented here. The patient has a history of bipolar disorder in remission but had an acute manic episode with psychotic features after resection of suprasellar meningioma. He presented with superimposed delirium that complicated the presentation. Because there was no effective resolution with medications, ECT was administered. This case documents the safe administration of ECT in complicated situations such as these. This case also demonstrates that ECT can be successfully administered in the presence of superimposed delirium and after a recent meningioma resection. Clinical skills and expertise are required to safely and effectively administer ECT in such cases. PMID:19935094

  20. Nondural-based lumbar clear cell meningioma. Case report.

    PubMed

    Holtzman, R N; Jormark, S C

    1996-02-01

    This 32-year-old man had noticed right leg pain for 4 years and developed classic right sciatica after heavy lifting, followed by episodes of buckling of both legs 1 month prior to admission. His medical history included congenital left abducens palsy. Examination revealed a right Lasègue's sign and Fajersztajn's sign with mild weakness of the right extensor hallucis longus. Magnetic resonance imaging revealed a 1.5 x 2.0-cm enhancing intradural lesion at the L3-4 level. Following laminectomy of L-3 and L-4 and intradural exposure, the tumor was found to be draped loosely by the roots of the cauda equina and attached to a single root without any adherence to dura. Transection of the adherent fascicles and typical microdissection of arachnoidal filaments permitted its complete removal without violation of the capsule, allowing the preservation of a large fascicle. The patient's recovery was uneventful. Postoperatively, a mild right lateral foot hypalgesia and diminution of the right ankle jerk implicated the S-1 root. Histological and immunohistochemical analyses diagnosed the specimen as a clear cell meningioma. PMID:8592230

  1. Tissue Engineering Strategies as Tools for Personalized Meningioma Treatment.

    PubMed

    Ferroni, Letizia; Della Puppa, Alessandro; D'Avella, Domenico; Isola, Maurizio; Scienza, Renato; Gardin, Chiara; Zavan, Barbara

    2015-07-01

    Pharmacogenomics, the science of how genetic makeup influences an individual's reaction to drugs, is an innovative tool for providing critical insights into how a patient will respond to a particular treatment. In the present work, we constructed cancer-like tissues to be used as tools for determining the most effective drug for an individual patient. Using tissue engineering strategies, we generated two different solid tumor-like tissues in vitro, a neuronal tumor (meningioma) and a nonmelanoma skin cancer. Samples were tested by both histological and genetic approaches (using a comparative genomic hybridization array, and the relative World Health Organization classification of the samples was compared with the results obtained by the molecular analyses. Our data confirmed the ability of the cells to maintain their phenotype in three-dimensional scaffolds as well as the strong relationship between chromosomal alterations and histological malignancy grades. We then validated the in vitro construction of tumor-like tissues as a potential tool for developing personalized drug treatments. PMID:25894852

  2. Meningothelial meningioma in a Malayan sun bear (Helarctos malayanus).

    PubMed

    Chien, Yao-Chun; Lien, Chen-Yeh; Guo, Jun-Cheng; Chin, Shih-Chien; Chang, Ya-Pei; Liu, Chen-Hsuan

    2013-09-01

    A 24-year-old, spayed female Malayan sun bear (Helarctos malayanus) in the Taipei Zoo (Taipei, Taiwan) showed clinical signs of slowly progressive anorexia, dullness, compulsive pacing, and circling. The animal subsequently developed acute severe stupor and persistent recumbency. Postcontrast study of computed tomography revealed a spheroid, extra-axial mass with strong but heterogeneous hyperattenuation in the left temporal lobe of the cerebrum. At necropsy, a solitary, well-circumscribed intracranial mass measuring 3 cm × 2.5 cm × 2 cm was attached to the left pyriform lobe with compression of the adjacent neuroparenchyma. Cytological examination obtained from the mass revealed large clumps and sheets of cohesive polyhedral cells with round nuclei, wispy cytoplasm, and indistinct cell borders. Microscopically, the mass was composed of densely packed round to polygonal cells arranged in lobules and small nests. Psammoma bodies, xanthomatous change, and cholesterol deposition were also noted. Immunohistochemical staining of the tumor was positive for vimentin, pancytokeratin, cytokeratin (CK)34BE12, neuron-specific enolase, and epithelial membrane antigen, but negative for glial fibrillary acidic protein and S100 protein. The cytological, histological, and immunohistochemical features were compatible with a meningothelial meningioma. PMID:23942899

  3. Management of Recurrent Trigeminal Neuralgia Associated with Petroclival Meningioma.

    PubMed

    Bir, Shyamal C; Maiti, Tanmoy Kumar; Bollam, Papireddy; Nanda, Anil

    2016-02-01

    Objective Petroclival meningioma (PM) presents with trigeminal neuralgia (TN) in < 5% of cases. Neurosurgeons often face the dilemma of formulating a treatment protocol when TN recurs. In this study, we sought to set up a protocol in patients with PM who had a recurrent TN. Materials and Methods We performed a retrospective review of 57 patients with PM. Of the 57 patients, only 7 patients presented with TN, and six patients experienced recurrent TN. The study population was evaluated clinically and radiographically after treatment. Results Overall improvement of pain control after various treatments was 67%, and tumor control was 100%. The pain-free period was 2 years for the Gamma Knife radiosurgery (GKRS) group and 4 years for the resection group when treated as a primary treatment (p = 0.034). Of the six patients, four patients had Barrow Neurosurgical Institute (BNI) score I (no TN, no medication), and two patients had BNI score III (some pain controlled with medication). The Karnofsky performance scale score was significantly improved after treatment compared with the pretreated status (78 versus 88; p = 0.044). Conclusion Microsurgical resection is superior to GKRS in achieving and maintaining pain-free status in patients with recurrent trigeminal pain associated with PM. PMID:26949588

  4. Foxc1 dependent mesenchymal signalling drives embryonic cerebellar growth

    PubMed Central

    Haldipur, Parthiv; Gillies, Gwendolyn S; Janson, Olivia K; Chizhikov, Victor V; Mithal, Divakar S; Miller, Richard J; Millen, Kathleen J

    2014-01-01

    Loss of Foxc1 is associated with Dandy-Walker malformation, the most common human cerebellar malformation characterized by cerebellar hypoplasia and an enlarged posterior fossa and fourth ventricle. Although expressed in the mouse posterior fossa mesenchyme, loss of Foxc1 non-autonomously induces a rapid and devastating decrease in embryonic cerebellar ventricular zone radial glial proliferation and concurrent increase in cerebellar neuronal differentiation. Subsequent migration of cerebellar neurons is disrupted, associated with disordered radial glial morphology. In vitro, SDF1α, a direct Foxc1 target also expressed in the head mesenchyme, acts as a cerebellar radial glial mitogen and a chemoattractant for nascent Purkinje cells. Its receptor, Cxcr4, is expressed in cerebellar radial glial cells and conditional Cxcr4 ablation with Nes-Cre mimics the Foxc1−/− cerebellar phenotype. SDF1α also rescues the Foxc1−/− phenotype. Our data emphasizes that the head mesenchyme exerts a considerable influence on early embryonic brain development and its disruption contributes to neurodevelopmental disorders in humans. DOI: http://dx.doi.org/10.7554/eLife.03962.001 PMID:25513817

  5. Cerebellar atrophy and prognosis after temporal lobe resection.

    PubMed Central

    Specht, U; May, T; Schulz, R; Rohde, M; Ebner, A; Schmidt, R C; Schütz, M; Wolf, P

    1997-01-01

    OBJECTIVE: Experimental data indicate inhibitory effects of the cerebellum on seizure activity. Structural damage such as cerebellar atrophy, which is a common finding in patients with chronic epilepsy, may reduce these effects. METHODS: Outcome after temporal lobectomy was studied in 78 consecutive patients, with or without cerebellar atrophy diagnosed by MRI. RESULTS: Thirty five patients (45%) showed cerebellar atrophy. At a mean follow up of 14.6 (range, 6-40) months, 50 patients (64%) had no postoperative seizures. In these patients, the frequency of cerebellar atrophy was significantly lower (34%) than in patients who relapsed (64%, p < 0.01). Occurrence of generalised tonic-clonic seizures (GTCS) within two years before surgery, occurrence of GTCS at any time preoperatively, long duration of epilepsy, and older age at surgery were also associated with recurrence of seizures. Multiple logistic regression analysis suggested occurrence of GTCS within two years before surgery and cerebellar atrophy as the main predictive indicators. When both factors were present, the percentage of patients remaining seizure free since surgery fell to 30%, compared with 60% when only GTCS were present, 78.6% when only cerebellar atrophy was present, and 87.5% when both factors were absent. CONCLUSIONS: Cerebellar atrophy shown by MRI was a frequent finding in surgically treated patients with temporal lobe epilepsy. The presence of cerebellar atrophy seems to worsen the prognosis after temporal lobe resection. Images PMID:9153610

  6. Pre- and Postnatal Neuroimaging of Congenital Cerebellar Abnormalities.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-02-01

    The human cerebellum has a protracted development that makes it vulnerable to a broad spectrum of developmental disorders including malformations and disruptions. Starting from 19 to 20 weeks of gestation, prenatal magnetic resonance imaging (MRI) can reliably study the developing cerebellum. Pre- and postnatal neuroimaging plays a key role in the diagnostic work-up of congenital cerebellar abnormalities. Diagnostic criteria for cerebellar malformations and disruptions are based mostly on neuroimaging findings. The diagnosis of a Dandy-Walker malformation is based on the presence of hypoplasia, elevation, and counterclockwise upward rotation of the cerebellar vermis and cystic dilatation of the fourth ventricle, which extends posteriorly filling out the posterior fossa. For the diagnosis of Joubert syndrome, the presence of the molar tooth sign (thickened, elongated, and horizontally orientated superior cerebellar peduncles and an abnormally deep interpeduncular fossa) is needed. The diagnostic criteria of rhombencephalosynapsis include a complete or partial absence of the cerebellar vermis and continuity of the cerebellar hemispheres across the midline. Unilateral cerebellar hypoplasia is defined by the complete aplasia or hypoplasia of one cerebellar hemisphere. Familiarity with these diagnostic criteria as well as the broad spectrum of additional neuroimaging findings is important for a correct pre- and postnatal diagnosis. A correct diagnosis is essential for management, prognosis, and counseling of the affected children and their family. PMID:26166429

  7. De novo cerebellar malignant glioma: A case report

    PubMed Central

    Matsumoto, Hiroaki; Yoshida, Yasuhisa

    2016-01-01

    Introduction Gliomas of the cerebellum are rare in adults, and their natural history and clinical behavior are not well known. Because cerebellar glioma is not usually diagnosed until clinical symptoms have appeared, no reports have described the developmental process of new cerebellar gliomas. We describe a case of de novo cerebellar anaplastic astrocytoma in which the developmental process was detected on magnetic resonance imaging (MRI). Presentation of case A 78-year-old man with a history of cerebral infarction was undergoing follow-up MRI every 6 months. This follow-up revealed a small abnormality in the left cerebellar hemisphere without clinical symptoms. Subsequent MRI showed lesion growth accompanying clinical symptoms. As cerebellar tumor was suspected, the lesion was extirpated. The histological diagnosis was anaplastic astrocytoma. Local recurrence developed and the patient died 20 months postoperatively. Discussion Cerebellar gliomas sometimes do not exhibit the common MRI findings of supratentorial gliomas, leading to difficulty with preoperative diagnosis. In this case, we initially diagnosed asymptomatic cerebellar infarction because the lesion was small and asymptomatic. The abnormal lesion gradually grew and clinical symptoms appeared. Cerebellar glioma may show few signs characteristic of tumor on MRI in the initial stages. Conclusion When MRI detects a new, faint abnormality in the cerebellum, close follow-up of clinical symptoms and MRI on suspicion of glioma is warranted PMID:27017277

  8. Increased cerebellar volume and BDNF level following quadrato motor training.

    PubMed

    Ben-Soussan, Tal Dotan; Piervincenzi, Claudia; Venditti, Sabrina; Verdone, Loredana; Caserta, Micaela; Carducci, Filippo

    2015-01-01

    Using whole-brain structural measures coupled to analysis of salivary brain-derived neurotrophic factor (BDNF), we demonstrate sensory motor training-induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level. PMID:25311848

  9. Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

    PubMed Central

    Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

    2015-01-01

    Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

  10. Humor and laughter in patients with cerebellar degeneration.

    PubMed

    Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

    2012-06-01

    Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation. PMID:22012411

  11. Distinct Critical Cerebellar Subregions for Components of Verbal Working Memory

    ERIC Educational Resources Information Center

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2012-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between…

  12. Cerebellar control of gait and interlimb coordination.

    PubMed

    Vinueza Veloz, María Fernanda; Zhou, Kuikui; Bosman, Laurens W J; Potters, Jan-Willem; Negrello, Mario; Seepers, Robert M; Strydis, Christos; Koekkoek, Sebastiaan K E; De Zeeuw, Chris I

    2015-11-01

    Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more complex, multi-joint motor behaviors, such as locomotion performance and adaptation during obstacle crossing, is not well understood. Here, we investigated these functions using the Erasmus Ladder in cell-specific mouse mutant lines that suffer from impaired Purkinje cell output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Δγ2), and granule cell output (α6-Cacna1a). We found that locomotion performance was severely impaired with small steps and long step times in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Δγ2 and not significantly affected in α6-Cacna1a mice. Locomotion adaptation triggered by pairing obstacle appearances with preceding tones at fixed time intervals was impaired in all four mouse lines, in that they all showed inaccurate and inconsistent adaptive walking patterns. Furthermore, all mutants exhibited altered front-hind and left-right interlimb coordination during both performance and adaptation, and inconsistent walking stepping patterns while crossing obstacles. Instead, motivation and avoidance behavior were not compromised in any of the mutants during the Erasmus Ladder task. Our findings indicate that cell type-specific abnormalities in cerebellar microcircuitry can translate into pronounced impairments in locomotion performance and adaptation as well as interlimb coordination, highlighting the general role of the cerebellar cortex in spatiotemporal control of complex multi-joint movements. PMID:25139623

  13. DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma.

    PubMed

    Rajaraman, Preetha; Hutchinson, Amy; Wichner, Sara; Black, Peter M; Fine, Howard A; Loeffler, Jay S; Selker, Robert G; Shapiro, William R; Rothman, Nathaniel; Linet, Martha S; Inskip, Peter D

    2010-01-01

    Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case-control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR(CT/TT) = 3.5; 95% confidence interval: 1.8-6.9; P(trend) .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P(trend) .01); MUTYH rs3219466 (P(trend) .02), and PCNA rs25406 (P(trend) .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P(trend) .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P(trend) .03) and ERCC5 rs17655 (P(trend) .05) variants and decreased for the PARP1 rs1136410 (P(trend) .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P(trend) .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma. PMID:20150366

  14. Yes-Associated Protein 1 Is Activated and Functions as an Oncogene in Meningiomas

    PubMed Central

    Baia, Gilson S.; Caballero, Otavia L.; Orr, Brent A.; Lal, Anita; Ho, Janelle S.Y.; Cowdrey, Cynthia; Tihan, Tarik; Mawrin, Christian; Riggins, Gregory J.

    2015-01-01

    The Hippo signaling pathway is functionally conserved in Drosophila melanogaster and mammals, and its proposed function is to control tissue homeostasis by regulating cell proliferation and apoptosis. The core components are composed of a kinase cascade that culminates with the phosphorylation and inhibition of Yes-associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm. In the absence of Hippo signaling, YAP1 translocates to the nucleus, associates with co-activators TEAD1-4, and functions as a transcriptional factor promoting the expression of key target genes. Components of the Hippo pathway are mutated in human cancers, and deregulation of this pathway plays a role in tumorigenesis. Loss of the NF2 tumor suppressor gene is the most common genetic alteration in meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo pathway. Here, we show that primary meningioma tumors have high nuclear expression of YAP1. In meningioma cells, Merlin expression is associated with phosphorylation of YAP1. Using an siRNA transient knockdown of YAP1 in NF2-mutant meningioma cells, we show that suppression of YAP1 impaired cell proliferation and migration. Conversely, YAP1 overexpression led to a strong augment of cell proliferation and anchorage-independent growth and restriction of cisplatin-induced apoptosis. In addition, expression of YAP1 in nontransformed arachnoidal cells led to the development of tumors in nude mice. Together, these findings suggest that in meningiomas, deregulation of the Hippo pathway is largely observed in primary tumors and that YAP1 functions as an oncogene promoting meningioma tumorigenesis. PMID:22618028

  15. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma.

    PubMed

    Norden, Andrew D; Raizer, Jeffrey J; Abrey, Lauren E; Lamborn, Kathleen R; Lassman, Andrew B; Chang, Susan M; Yung, W K Alfred; Gilbert, Mark R; Fine, Howard A; Mehta, Minesh; Deangelis, Lisa M; Cloughesy, Timothy F; Robins, H Ian; Aldape, Kenneth; Dancey, Janet; Prados, Michael D; Lieberman, Frank; Wen, Patrick Y

    2010-01-01

    There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29-81) and median Karnofsky performance status (KPS) score 90 (range 60-100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted. PMID:19562255

  16. Phase II Trials of Erlotinib or Gefitinib in Patients with Recurrent Meningioma

    PubMed Central

    Norden, Andrew D.; Raizer, Jeffrey J.; Abrey, Lauren E.; Lamborn, Kathleen R.; Lassman, Andrew B.; Chang, Susan M.; Yung, W.K. Alfred; Gilbert, Mark R.; Fine, Howard A.; Mehta, Minesh; DeAngelis, Lisa M.; Cloughesy, Timothy F.; Robins, H. Ian; Aldape, Kenneth; Dancey, Janet; Prados, Michael D.; Lieberman, Frank; Wen, Patrick Y.

    2013-01-01

    There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29–81) and median Karnofsky performance status (KPS) score 90 (range 60–100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted. PMID:19562255

  17. Characterization of a gene which is disrupted by a balanced translocation in a meningioma

    SciTech Connect

    Zwarthoff, E.C.; Riegman, P.H.J.; Groen, N.A.

    1994-09-01

    Meningiomas are tumors of the central nervous system in which loss of heterozygosity for markers on the long arm of chromosome 22 is a frequent event. We have previously described a balanced t(4;22)(p16;q11), which was observed in meningioma 32. We have cloned a gene (MN1), which is disrupted by the translocation breakpoint. The gene spans about 70 kb on chromosome 22q11. A total of 7.5 kb of overlapping cDNA clones were isolated. A comparison of the cDNA clones with the genomic cosmid contig from this region shows that the MN1 gene consists of at least two large exons of approximately 4.7 kb and 2.8 kb. Sequence analysis of the MN1 cDNA revealed two open reading frames (ORFs) of 1 and 2.3 kb which are separated by a region of approximately 1 kb with stop codons in all reading frames. The second ORF is disrupted by the t(4;22) translocation. In the region between the ORFs 2 CAG repeats have been found. These repeats do not display length variation in meningiomas. There is no obvious homology in the nucleotide and putative amino acid sequences with other known genes. The MN1 gene is highly conserved in evolution. The approximately 8 kb MN1 mRNA is ubiquitously expressed with an alternative 4.5 kb transcript in skeletal muscle. In meningiomas the expression pattern is very variable and a 6.5 kb transcript is sometimes also observed. Some, including meningioma 32, show no expression suggesting that the gene could function as a tumor suppressor gene for meningeal cells. Paradoxically, however, a very high expression is sometimes also observed in meningiomas.

  18. Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas

    SciTech Connect

    Deprez, R.H.L.; Groen, N.A.; Zwarthoff, E.C.; Hagemeijer, A.; Van Drunen, E.; Bootsma, D.; Koper, J.W.; Avezaat, C.J.J. ); Bianchi, A.B.; Seizinger, B.R. )

    1994-06-01

    The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-related tumors, the authors have used reverse transcriptase-PCR amplification followed by SSCP and DNA sequence analysis to screen for mutations in the coding region of the NF2 gene. Analysis of the NF2 gene transcript in 53 unrelated patients with meningiomas and vestibular schwannomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tumors the NF2 gene functions as a recessive tumor-suppressor gene. The mutations detected resulted mostly in frameshifts, predicting truncations starting within the N-terminal half of the putative protein. 23 refs., 2 figs. 3 tabs.

  19. Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system.

    PubMed

    Yuzawa, Sayaka; Nishihara, Hiroshi; Yamaguchi, Shigeru; Mohri, Hiromi; Wang, Lei; Kimura, Taichi; Tsuda, Masumi; Tanino, Mishie; Kobayashi, Hiroyuki; Terasaka, Shunsuke; Houkin, Kiyohiro; Sato, Norihiro; Tanaka, Shinya

    2016-07-01

    Recent genetic analyses using next-generation sequencers have revealed numerous genetic alterations in various tumors including meningioma, which is the most common primary brain tumor. However, their use as routine laboratory examinations in clinical applications for tumor genotyping is not cost effective. To establish a clinical sequencing system for meningioma and investigate the clinical significance of genotype, we retrospectively performed targeted amplicon sequencing on 103 meningiomas and evaluated the association with clinicopathological features. We designed amplicon-sequencing panels targeting eight genes including NF2 (neurofibromin 2), TRAF7, KLF4, AKT1, and SMO. Libraries prepared with genomic DNA extracted from PAXgene-fixed paraffin-embedded tissues of 103 meningioma specimens were sequenced using the Illumina MiSeq. NF2 loss in some cases was also confirmed by interphase-fluorescent in situ hybridization. We identified NF2 loss and/or at least one mutation in NF2, TRAF7, KLF4, AKT1, and SMO in 81 out of 103 cases (79%) by targeted amplicon sequencing. On the basis of genetic status, we categorized meningiomas into three genotype groups: NF2 type, TRAKLS type harboring mutation in TRAF7, AKT1, KLF4, and/or SMO, and 'not otherwise classified' type. Genotype significantly correlated with tumor volume, tumor location, and magnetic resonance imaging findings such as adjacent bone change and heterogeneous gadolinium enhancement, as well as histopathological subtypes. In addition, multivariate analysis revealed that genotype was independently associated with risk of recurrence. In conclusion, we established a rapid clinical sequencing system that enables final confirmation of meningioma genotype within 7 days turnaround time. Our method will bring multiple benefits to neuropathologists and neurosurgeons for accurate diagnosis and appropriate postoperative management. PMID:27102344

  20. Assessment of Autoantibodies to Meningioma in a Population-based Study

    PubMed Central

    Wiemels, Joseph L.; Bracci, Paige M.; Wrensch, Margaret; Schildkraut, Joellen; Bondy, Melissa; Pfefferle, Jon; Zhou, Mi; Sison, Jennette; Calvocoressi, Lisa; Claus, Elizabeth B.

    2013-01-01

    Meningioma is an intracranial tumor with few confirmed risk factors. Recent research points to an impact on meningioma risk from factors related to immune function and development, such as allergy, immunoglobulin E, and Varicella infection status. To further explore an association with immune function, the authors assessed individual seroreactivity to meningioma tumor-associated antigens among participants enrolled in a multicenter, population-based US case-control study of meningioma (2006–2009). Serum samples from cases (n = 349) and controls (n = 348) were screened for autoantibody reactivity to 3 proteins identified in previous studies: enolase 1 (ENO1), NK-tumor recognition protein (NKTR), and nuclear mitotic apparatus protein 1 (NUMA1). Case-control differences were not strong overall (adjusted odds ratio (OR)ENO1 (continuous) = 1.1, 95% confidence interval (CI): 0.6, 1.9 (Ptrend = 0.3); adjusted ORNKTR (continuous) = 1.3, 95% CI: 0.7, 2.4 (Ptrend = 0.02); and adjusted ORNUMA1 (continuous) = 1.1, 95% CI: 0.7, 1.8 (Ptrend = 0.06)); however, antibodies to NKTR and NUMA1 were detected at higher levels in cases than in controls, particularly among men (for men, adjusted ORENO1 (continuous) = 1.6, 95% CI: 0.5, 4.7 (Ptrend = 0.24); adjusted ORNKTR (continuous) = 4.3, 95% CI: 1.2, 15 (Ptrend = 0.009); and adjusted ORNUMA1 (continuous) = 3.6, 95% CI: 1.1, 11 (Ptrend = 0.006)). These results indicate that men with meningioma commonly react with a serologic antimeningioma response; if supported by further research, this finding suggests a distinctive etiology for meningioma in men. PMID:23221727

  1. Does Histologic Subtype Influence the Post-Operative Outcome in Spinal Meningioma?

    PubMed Central

    Zham, Hanieh; Moradi, Afshin; Rakhshan, Azadeh; Zali, Alireza; Rahbari, Ali; Raee, Mohammadreza; Ashrafi, Farzad; Ahadi, Mahsa; Larijani, Leila; Baikpour, Masoud; Khayamzadeh, Maryam

    2016-01-01

    Background Postoperative outcome of spinal meningiomas is an important issue in surgery decision-making. There are limited and conflicting data in the literature about the prognostic factors influencing recovery, especially about the histopathologic subtypes. Objectives This study was carried out to evaluate the effect of some of these factors on postoperative outcome. Patients and Methods This study was performed on 39 patients operated for spinal meningioma between October 1998 and January 2012; their histopathologic subtype was determined according to WHO criteria. The follow up period ranged between 8 - 120 months. The influence of histopathologic subtype, grade, age, sex, surgical approach, local adhesion and anatomical location was assessed according to Frankel classification of neurologic deficit. Results From a total number of 39 spinal meningiomas, 34 cases were WHO grade I, from which 15 cases were psammomatous, 7 cases were meningothelial, 9 cases were transitional and 3 cases were fibroblastic. Five cases were grade II, 3 of which had clear cell appearance and the remaining 2 had chordoid appearance. The mean age was 51.6 (22 to 76) years; 25 cases were female and 14 cases were male. This study revealed that grade II meningioma cases had poor prognosis in all 5 cases and psammomatous subtype had poor postoperative outcome in 40% of cases while the other subtypes had good outcome in all cases (P = 0.026). Cervical location of the tumor was also related with poor outcome in 37.5% of the cases, while 22.5% had poor outcome in other locations (P = 0.029). Age below and above 45 years and sex had no significant influence on the outcome. Conclusions Spinal meningiomas of psammomatous type and grade II spinal meningiomas are associated with less favorable postoperative neurologic outcome. Cervical location has also a negative correlation with a good outcome. PMID:27482326

  2. Differentiation between meningiomas and other CNS tumors by simultaneous somatostatin receptor and brain scintigraphy

    SciTech Connect

    Haldemann, A.R.; Luescher, D.; Sulzer, M.

    1994-05-01

    Since the differentiation between meningiomas and some other CNS tumors may be difficult in certain localizations, biopsy is mandatory, even in patients with meningiomas who are to be treated with percutaneous radiotherapy alone. The high density of somatostatin receptors (SSR) in meningiomas has led us to compare patients with meningiomas and other CNS tumors by simultaneous SSR and brain scintigraphy (BS) using 74 MBq 111In octreotide and 740 MBq 99mTc DTPA injected two hours later. SPECT was performed on a 3-head gamma camera 4 hours after 111In octreotide injection in multiple peak acquisition mode in 35 patients with radiologically documented CNS tumors. In positive scans, a tumor ROI was defined manually in the transverse 111In slice with highest tumor contrast and the identical tumor ROI was transferred to the corresponding 99mTc slice. A SSR to BS index was then calculated from the ratio of 111In to 99mTc counts after normalizing for identical total counts in the slices. in negative scans, the SSR to BS index was set to be 1.0. In 7 meningiomas, the SSR to BS index was 2.64{plus_minus}0.76. In 28 other CNS tumors (7 gliomas I-111, 4 neurinomas, 3 glial reactions, 3 metastases, 3 gliomas IV, 2 ependymomas, 1 chordoma, 1 NHL; plus 4 inoperable, radiologically diagnosed glioblastomas) 1.06{plus_minus}0.13. Thus, a highly significant difference was found between these two groups (p<0.0001). It is concluded that combined SSR and BS allows excellent discrimination between meningiomas and other CNS tumors and may become a non-invasive alternative to biopsy in selected clinical situations.

  3. Characterization of insulin-like growth factor I and epidermal growth factor receptors in meningioma

    SciTech Connect

    Kurihara, M.; Tokunaga, Y.; Tsutsumi, K.; Kawaguchi, T.; Shigematsu, K.; Niwa, M.; Mori, K. )

    1989-10-01

    Receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were localized and characterized in eight samples of human meningioma (four fibrous, two meningothelial, and two angioblastic types), using quantitative autoradiographic techniques. Effects of both growth factors on deoxyribonucleic acid (DNA) synthesis in the cultured meningioma cells were examined. High numbers of specific binding sites for both IGF-I and EGF were homogeneously present in tissue sections derived from fibrous and meningothelial types of meningiomas, whereas binding sites for these growth factors were not detectable in adjacent leptomeninges. While relatively large numbers of IGF-I binding sites were located in the wall of the intratumoral vasculature, the number of binding sites in the stromal component was lower in angioblastic-type meningiomas, including a low number of EGF binding sites detected only in the stromal portion. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for both IGF-I and EGF in the meningiomas examined (dissociation constant (Kd) = 0.6 to 2.9 nM, and the maximum number of binding sites (Bmax) = 16 to 80 fmol/mg for IGF-I; and Kd = 0.6 to 4.0 nM, Bmax = 3 to 39 fmol/mg for EGF). Both growth factors increased the synthesis of DNA, in a dose-dependent manner, as measured by 3H-thymidine incorporation. The combination of IGF-I and EGF synergistically stimulated the synthesis of DNA, and the effects seen with 10% fetal bovine serum could be reproduced at a concentration of 10(-10) M. These observations can be interpreted to mean that both IGF-I and EGF may be involved in the growth modulation of meningiomas, possibly through paracrine or autocrine mechanisms.

  4. Otogenic cerebellar abscess: a case report.

    PubMed

    Richter, Gresham T; Smith, Jason A; Dornhoffer, John L

    2009-04-01

    This case report describes the gradual deterioration of a healthy, highly functioning man who initially presented with a draining right ear. The patient's indolent neurologic decline and referral to an otologist ultimately led to the diagnosis and treatment of an otogenic cerebellar abscess, an increasingly rare intracranial complication of otitis media. We report this case to illustrate that severe complications of chronic otitis media still occur in the United States, to stress the importance of clinical suspicion in the postantibiotic era, and to review the literature regarding the most appropriate time to perform the otologic portion of the surgery. PMID:19358116

  5. The physiological basis of therapies for cerebellar ataxias.

    PubMed

    Mitoma, Hiroshi; Manto, Mario

    2016-09-01

    Cerebellar ataxias represent a group of heterogeneous disorders impacting on activities of daily living and quality of life. Various therapies have been proposed to improve symptoms in cerebellar ataxias. This review examines the physiological background of the various treatments currently administered worldwide. We analyze the mechanisms of action of drugs with a focus on aminopyridines and other antiataxic medications, of noninvasive cerebellar stimulation, and of motor rehabilitation. Considering the cerebellum as a controller, we propose the novel concept of 'restorable stage'. Because of its unique anatomical architecture and its diffuse connectivity in particular with the cerebral cortex, keeping in mind the anatomophysiology of the cerebellar circuitry is a necessary step to understand the rationale of therapies of cerebellar ataxias and develop novel therapeutic tools. PMID:27582895

  6. New evidence for the cerebellar involvement in personality traits

    PubMed Central

    Picerni, Eleonora; Petrosini, Laura; Piras, Fabrizio; Laricchiuta, Daniela; Cutuli, Debora; Chiapponi, Chiara; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    Following the recognition of its role in sensory-motor coordination and learning, the cerebellum has been involved in cognitive, emotional, and even personality domains. This study investigated the relationships between cerebellar macro- and micro-structural variations and temperamental traits measured by Temperament and Character Inventory (TCI). High resolution T1-weighted, and Diffusion Tensor Images of 100 healthy subjects aged 18–59 years were acquired by 3 Tesla Magnetic Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM) or White Matter (WM) volumes, GM Mean Diffusivity (MD), and WM Fractional Anisotropy (FA) were used as dependent variables, TCI scores as regressors, gender, age, and education years as covariates. Novelty Seeking scores were associated positively with the cerebellar GM volumes and FA, and negatively with MD. No significant association between Harm Avoidance, Reward Dependence or Persistence scores and cerebellar structural measures was found. The present data put toward a cerebellar involvement in the management of novelty. PMID:24106465

  7. The physiological basis of therapies for cerebellar ataxias

    PubMed Central

    Mitoma, Hiroshi; Manto, Mario

    2016-01-01

    Cerebellar ataxias represent a group of heterogeneous disorders impacting on activities of daily living and quality of life. Various therapies have been proposed to improve symptoms in cerebellar ataxias. This review examines the physiological background of the various treatments currently administered worldwide. We analyze the mechanisms of action of drugs with a focus on aminopyridines and other antiataxic medications, of noninvasive cerebellar stimulation, and of motor rehabilitation. Considering the cerebellum as a controller, we propose the novel concept of ‘restorable stage’. Because of its unique anatomical architecture and its diffuse connectivity in particular with the cerebral cortex, keeping in mind the anatomophysiology of the cerebellar circuitry is a necessary step to understand the rationale of therapies of cerebellar ataxias and develop novel therapeutic tools. PMID:27582895

  8. Radiation-induced meningiomas after BNCT in patients with malignant glioma.

    PubMed

    Kageji, T; Sogabe, S; Mizobichi, Y; Nakajima, K; Shinji, N; Nakagawa, Y

    2015-12-01

    Of the 180 patients with malignant brain tumors whom we treated with boron neutron capture therapy (BNCT) since 1968, only one (0.56%) developed multiple radiation-induced meningiomas. The parasagittal meningioma that had received 42 Gy (w) for BNCT showed more rapid growth on Gd-enhanced MRI scans and more atypical features on histopathologic studies than the temporal convexity tumor that had received 20 Gy (w). Long-term follow up MRI studies are necessary in long-survivors of malignant brain tumors treated by BNCT. PMID:26122975

  9. Diagnostic and prognostic significance of genetic regional heterogeneity in meningiomas1

    PubMed Central

    Pfisterer, Wolfgang K.; Hank, Nicole C.; Preul, Mark C.; Hendricks, William P.; Pueschel, Jeanette; Coons, Stephen W.; Scheck, Adrienne C.

    2004-01-01

    We analyzed the frequency and regional distribution of cells with genetic abnormalities of chromosomes 1, 14, and 22 in meningiomas. This data was evaluated for correlation to the clinical outcome of the patients. Eight defined areas of each of 77 paraffin-embedded meningioma samples (59 grade I, 13 grade II, and 5 grade III) were analyzed by fluorescent in situ hybridization using bacterial artificial chromosome probes localized to chromosomes 1p36.32, 1q25.3, 14q13.3, 14q32.12, 22q11.2, and 22q12.1-3. Chromosome deletion was considered to be regionally heterogeneous if <7 regions showed cells with chromosome deletions. Deletion of 1p occurred in 35% of the grade I tumors. Distribution of cells with 1p deletion was regionally heterogeneous in 25% and homogeneous in 10% of grade I tumors. Distribution of cells with deletion of 1p was regionally heterogeneous in 23% and homogeneous in 69% of the grade II tumors. All grade III meningiomas had homogeneous distribution of cells with deletion of chromosome 1p. Distribution of cells with deletion of 14q was regionally heterogeneous in 27% and homogeneous in 2% of the grade I meningiomas, heterogeneous in 31% and homogeneous in 62% of the grade II tumors, and heterogeneous in 40% and homogeneous in 60% of the grade III meningiomas. Distribution of cells with deletion of 22q was regionally heterogeneous in 15% and homogeneous in 3% of the grade I tumors, heterogeneous in 15% and homogeneous in 31% of grade II tumors, and homogeneous in 20% of the grade III meningiomas. Distribution of cells with trisomy 22q was regionally heterogeneous in 10% of grade I tumors, heterogeneous in 23% of grade II, and homogeneous in 80% of grade III meningiomas. The proportion of patients with a deletion of 22q (either homogeneous or heterogeneous) who had recurrence was greater than the proportion of those without 22q deletion who had recurrence, and deletion of 22q was significantly associated with radiologically detected recurrence (P < 0

  10. Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

    PubMed Central

    Bekelis, Kimon; Valdés, Pablo A.; Erkmen, Kadir; Leblond, Frederic; Kim, Anthony; Wilson, Brian C.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

    2011-01-01

    Object Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection. Methods A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches. Results The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological

  11. Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis

    PubMed Central

    Sergentanis, Theodoros N.; Tsivgoulis, Georgios; Perlepe, Christina; Ntanasis-Stathopoulos, Ioannis; Tzanninis, Ioannis-Georgios; Sergentanis, Ioannis N.; Psaltopoulou, Theodora

    2015-01-01

    Objective This meta-analysis aims to examine the association between being overweight/obese and risk of meningiomas and gliomas as well as overall brain/central nervous system (CNS) tumors. Study Design Potentially eligible publications were sought in PubMed up to June 30, 2014. Random-effects meta-analysis and dose-response meta-regression analysis was conducted. Cochran Q statistic, I-squared and tau-squared were used for the assessment of between-study heterogeneity. The analysis was performed using Stata/SE version 13 statistical software. Results A total of 22 studies were eligible, namely 14 cohort studies (10,219 incident brain/CNS tumor cases, 1,319 meningioma and 2,418 glioma cases in a total cohort size of 10,143,803 subjects) and eight case-control studies (1,009 brain/CNS cases, 1,977 meningioma cases, 1,265 glioma cases and 8,316 controls). In females, overweight status/obesity was associated with increased risk for overall brain/CNS tumors (pooled RR = 1.12, 95%CI: 1.03–1.21, 10 study arms), meningiomas (pooled RR = 1.27, 95%CI: 1.13–1.43, 16 study arms) and gliomas (pooled RR = 1.17, 95%CI: 1.03–1.32, six arms). Obese (BMI>30 kg/m2) females seemed particularly aggravated in terms of brain/CNS tumor (pooled RR = 1.19, 95%CI: 1.05–1.36, six study arms) and meningioma risk (pooled RR = 1.48, 95%CI: 1.28–1.71, seven arms). In males, overweight/obesity status correlated with increased meningioma risk (pooled RR = 1.58, 95%CI: 1.22–2.04, nine study arms), whereas the respective association with overall brain/CNS tumor or glioma risk was not statistically significant. Dose-response meta-regression analysis further validated the findings. Conclusion Our findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males. PMID:26332834

  12. Strategic and Technical Considerations for the Endovascular Embolization of Intracranial Meningiomas.

    PubMed

    James, Robert F; Kramer, Daniel R; Page, Paul S; Gaughen, John R; Martin, Lacey B; Mack, William J

    2016-04-01

    Endovascular embolization is a frequently used adjunct to operative resection of meningiomas. Embolization may decrease intraoperative blood loss, operative time, and surgical difficulty associated with resection. The specific clinical applications of this treatment have not been defined clearly. Procedural indications, preferred embolic agent, and latency until tumor resection all differ across operators. It is clear that strategic patient selection, comprehensive anatomic understanding, and sound operative technique are critical to the success of the embolization procedure. This article reviews the management and technical considerations associated with preoperative meningioma embolization. PMID:27012380

  13. Insights into cerebellar development and medulloblastoma.

    PubMed

    Bihannic, Laure; Ayrault, Olivier

    2016-01-01

    Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models. PMID:26688373

  14. Favorable Outcomes of Pediatric Patients Treated With Radiotherapy to the Central Nervous System Who Develop Radiation-Induced Meningiomas

    SciTech Connect

    Galloway, Thomas J.; Indelicato, Daniel J.; Amdur, Robert J.; Swanson, Erika L.; Morris, Christopher G.; Marcus, Robert B.

    2011-01-01

    Purpose: To report the outcome of patients treated at the University of Florida who developed meningiomas after radiation to the central nervous system (CNS) for childhood cancer. Methods and Materials: We retrospectively identified 10 patients aged {<=}19 years who received radiotherapy to sites in the craniospinal axis and subsequently developed a meningioma. We report the histology of the radiation-induced meningioma, treatment received, and ultimate outcome among this cohort of patients. Results: Meningioma was diagnosed at a median of 23.5 years after completion of the primary radiation. Fifty percent of second meningiomas were World Health Organization Grade 2 (atypical) or higher. All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). The actuarial event-free survival and overall survival rate at 5 years after treatment for a radiation-induced meningioma was 89%. Three patients who underwent resection for retreatment experienced a Grade 3 toxicity. Conclusions: Radiation-induced meningiomas after treatment of pediatric CNS tumors are effectively managed with single-modality therapy. Such late-effect data inform the overall therapeutic ratio and support the continued role of selective irradiation in managing pediatric CNS malignancies.

  15. Fractionated Stereotactic Radiotherapy in Patients With Optic Nerve Sheath Meningioma

    SciTech Connect

    Paulsen, Frank; Doerr, Stefan; Wilhelm, Helmut; Becker, Gerd; Bamberg, Michael; Classen, Johannes

    2012-02-01

    Purpose: To evaluate the effectiveness of fractionated stereotactic radiotherapy (SFRT) in the treatment of optic nerve sheath meningioma (ONSM). Methods and Materials: Between 1993 and 2005, 109 patients (113 eyes) with primary (n = 37) or secondary (n = 76) ONSM were treated according to a prospective protocol with SFRT to a median dose of 54 Gy. All patients underwent radiographic, ophthalmologic, and endocrine analysis before and after SFRT. Radiographic response, visual control, and late side effects were endpoints of the analysis. Results: Median time to last clinical, radiographic, and ophthalmologic follow up was 30.2 months (n = 113), 42.7 months (n = 108), and 53.7 months (n = 91), respectively. Regression of the tumor was observed in 5 eyes and progression in 4 eyes, whereas 104 remained stable. Visual acuity improved in 12, deteriorated in 11, and remained stable in 68 eyes. Mean visual field defects reduced from 33.6% (n = 90) to 17.8% (n = 56) in ipsilateral and from 10% (n = 94) to 6.7% (n = 62) in contralateral eyes. Ocular motility improved in 23, remained stable in 65, and deteriorated in 3 eyes. Radiographic tumor control was 100% at 3 years and 98% at 5 years. Visual acuity was preserved in 94.8% after 3 years and in 90.9% after 5 years. Endocrine function was normal in 90.8% after 3 years and in 81.3% after 5 years. Conclusions: SFRT represents a highly effective treatment for ONSM. Interdisciplinary counseling of the patients is recommended. Because of the high rate of preservation of visual acuity we consider SFRT the standard approach for the treatment of ONSM. Prolonged observation is warranted to more accurately assess late visual impairment. Moderate de-escalation of the radiation dose might improve the preservation of visual acuity and pituitary gland function.

  16. Recurrent petroclival meningiomas: clinical characteristics, management, and outcomes.

    PubMed

    Li, Da; Hao, Shu-Yu; Wang, Liang; Tang, Jie; Xiao, Xin-Ru; Jia, Gui-Jun; Wu, Zhen; Zhang, Li-Wei; Zhang, Jun-Ting

    2015-01-01

    This study seeks to elucidate the prognostic predictors and outcomes of recurrent/progressive petroclival meningiomas (PCMs). We reviewed our cohort of 39 recurrent/progressive PCMs (27 females, 69.2%) and analyzed the results from the literature. Twenty-three patients underwent reoperations, 2 received radiotherapy alone, and 14 declined any treatment. During a follow-up of 70.4 months, 7 patients experienced a 2nd recurrence/progression (R/P) and 18 patients died. In the 23 patients, gross total resection (GTR), subtotal resection (STR), and partial resection (PR) were achieved in 8, 8, and 7 patients, respectively. The percentage of the 2nd R/P-free survival of GTR, STR, and PR was 88%, 67%, and 40%, respectively. The overall survival following the 1st R/P of GTR, STR, and PR was 88%, 63%, and 33%, respectively. Patients rejecting treatment suffered from significantly poor overall survival (7%; p = 0.001) and short survival duration (42.0 months; p = 0.016) compared with that of the patients receiving treatment (67% and 86.9 months). The GTR was the only independent favorable predictor. In the 21 included studies with 98 recurrent/progressive PCM patients, 17 patients presented with a 2nd R/P and 10 died of a 2nd R/P; patients undergoing observation had a significantly poor tumor regrowth control rate compared with patients undergoing surgery (p = 0.004) or radiotherapy alone (p < 0.001). Proactive treatment should be performed for patients with recurrent/progressive PCMs. Observation can lead to relentless outcome. GTR as a preferential therapeutic strategy should be pursued as far as possible on the condition of minimal functional impairment. PMID:25319087

  17. Prenatal Cerebellar Disruptions: Neuroimaging Spectrum of Findings in Correlation with Likely Mechanisms and Etiologies of Injury.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    There is increasing evidence that the cerebellum is susceptible to prenatal infections and hemorrhages and that congenital morphologic anomalies of the cerebellum may be caused by disruptive (acquired) causes. Starting from the neuroimaging pattern, this report describes a spectrum of prenatal cerebellar disruptions including cerebellar agenesis, unilateral cerebellar hypoplasia, cerebellar cleft, global cerebellar hypoplasia, and vanishing cerebellum in Chiari type II malformation. The neuroimaging findings, possible causative disruptive events, and clinical features of each disruption are discussed. Recognition of cerebellar disruptions and their differentiation from cerebellar malformations is important in terms of diagnosis, prognosis, and genetic counselling. PMID:27423799

  18. Substantia nigra reticulata neurons during sleep-waking states: relation with ponto-geniculo-occipital waves.

    PubMed

    Datta, S; Curró Dossi, R; Paré, D; Oakson, G; Steriade, M

    1991-12-01

    We have previously hypothesized that the spike bursts of brainstem peribrachial (PB) neurons, leading to ponto-geniculo-occipital (PGO) waves in thalamocortical systems, are triggered by phasic hyperpolarizations of sufficient magnitude or by excitatory inputs reaching a steadily hyperpolarized membrane. We have proposed that the source of these hyperpolarizing actions are substantia nigra pars reticulata (SNr) cells that project to, and exert inhibitory effects upon, PB neurons. Here we tested this hypothesis by recording antidromically identified SNr-PB cells in chronically implanted, naturally sleeping cats. A subpopulation of SNr-PB cells exhibited tonically increased firing preceding by 70-200 ms the thalamic PGO wave. These data support the hypothesis that an enhancement in SNr-cells' discharges may lead to hyperpolarization of PB neurons, with the consequence of spike bursts in one class of PGO-related PB-thalamic neurons. PMID:1814553

  19. Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

    PubMed Central

    Passot, Jean-Baptiste; Sheynikhovich, Denis; Duvelle, Éléonore; Arleo, Angelo

    2012-01-01

    Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation. PMID:22485133

  20. Neural correlates of impaired emotional face recognition in cerebellar lesions.

    PubMed

    Adamaszek, Michael; Kirkby, Kenneth C; D'Agata, Fedrico; Olbrich, Sebastian; Langner, Sönke; Steele, Christopher; Sehm, Bernhard; Busse, Stefan; Kessler, Christof; Hamm, Alfons

    2015-07-10

    Clinical and neuroimaging data indicate a cerebellar contribution to emotional processing, which may account for affective-behavioral disturbances in patients with cerebellar lesions. We studied the neurophysiology of cerebellar involvement in recognition of emotional facial expression. Participants comprised eight patients with discrete ischemic cerebellar lesions and eight control patients without any cerebrovascular stroke. Event-related potentials (ERP) were used to measure responses to faces from the Karolinska Directed Emotional Faces Database (KDEF), interspersed in a stream of images with salient contents. Images of faces augmented N170 in both groups, but increased late positive potential (LPP) only in control patients without brain lesions. Dipole analysis revealed altered activation patterns for negative emotions in patients with cerebellar lesions, including activation of the left inferior prefrontal area to images of faces showing fear, contralateral to controls. Correlation analysis indicated that lesions of cerebellar area Crus I contribute to ERP deviations. Overall, our results implicate the cerebellum in integrating emotional information at different higher order stages, suggesting distinct cerebellar contributions to the proposed large-scale cerebral network of emotional face recognition. PMID:25912431

  1. Cerebellar Processing of Sensory Inputs Primes Motor Cortex Plasticity

    PubMed Central

    Velayudhan, B.; Hubsch, C.; Pradeep, S.; Roze, E.; Vidailhet, M.; Meunier, S.; Kishore, A.

    2013-01-01

    Plasticity of the human primary motor cortex (M1) has a critical role in motor control and learning. The cerebellum facilitates these functions using sensory feedback. We investigated whether cerebellar processing of sensory afferent information influences the plasticity of the primary motor cortex (M1). Theta-burst stimulation protocols (TBS), both excitatory and inhibitory, were used to modulate the excitability of the posterior cerebellar cortex and to condition an ongoing M1 plasticity. M1 plasticity was subsequently induced in 2 different ways: by paired associative stimulation (PAS) involving sensory processing and TBS that exclusively involves intracortical circuits of M1. Cerebellar excitation attenuated the PAS-induced M1 plasticity, whereas cerebellar inhibition enhanced and prolonged it. Furthermore, cerebellar inhibition abolished the topography-specific response of PAS-induced M1 plasticity, with the effects spreading to adjacent motor maps. Conversely, cerebellar excitation had no effect on the TBS-induced M1 plasticity. This demonstrates the key role of the cerebellum in priming M1 plasticity, and we propose that it is likely to occur at the thalamic or olivo-dentate nuclear level by influencing the sensory processing. We suggest that such a cerebellar priming of M1 plasticity could shape the impending motor command by favoring or inhibiting the recruitment of several muscle representations. PMID:22351647

  2. Developmental dyslexia and widespread activation across the cerebellar hemispheres.

    PubMed

    Baillieux, Hanne; Vandervliet, Everhard J M; Manto, Mario; Parizel, Paul M; De Deyn, Peter P; Mariën, Peter

    2009-02-01

    Developmental dyslexia is the most common learning disability in school-aged children with an estimated incidence of five to ten percent. The cause and pathophysiological substrate of this developmental disorder is unclear. Recently, a possible involvement of the cerebellum in the pathogenesis of dyslexia has been postulated. In this study, 15 dyslexic children and 7 age-matched control subjects were investigated by means of functional neuroimaging (fMRI) using a noun-verb association paradigm. Comparison of activation patterns between dyslexic and control subjects revealed distinct and significant differences in cerebral and cerebellar activation. Control subjects showed bilaterally well-defined and focal activation patterns in the frontal and parietal lobes and the posterior regions of the cerebellar hemispheres. The dyslexic children, however, presented widespread and diffuse activations on the cerebral and cerebellar level. Cerebral activations were found in frontal, parietal, temporal and occipital regions. Activations in the cerebellum were found predominantly in the cerebellar cortex, including Crus I, Crus II, hemispheric lobule VI, VII and vermal lobules I, II, III, IV and VII. This preliminary study is the first to reveal a significant difference in cerebellar functioning between dyslexic children and controls during a semantic association task. As a result, we propose a new hypothesis regarding the pathophysiological mechanisms of developmental dyslexia. Given the sites of activation in the cerebellum in the dyslexic group, a defect of the intra-cerebellar distribution of activity is suspected, suggesting a disorder of the processing or transfer of information within the cerebellar cortex. PMID:18986695

  3. Update on the pharmacotherapy of cerebellar and central vestibular disorders.

    PubMed

    Kalla, Roger; Teufel, Julian; Feil, Katharina; Muth, Caroline; Strupp, Michael

    2016-04-01

    An overview of the current pharmacotherapy of central vestibular syndromes and the most common forms of central nystagmus as well as cerebellar disorders is given. 4-aminopyridine (4-AP) is recommended for the treatment of downbeat nystagmus, a frequent form of acquired persisting fixation nystagmus, and upbeat nystagmus. Animal studies showed that this non-selective blocker of voltage-gated potassium channels increases Purkinje cell excitability and normalizes the irregular firing rate, so that the inhibitory influence of the cerebellar cortex on vestibular and deep cerebellar nuclei is restored. The efficacy of 4-AP in episodic ataxia type 2, which is most often caused by mutations of the PQ-calcium channel, was demonstrated in a randomized controlled trial. It was also shown in an animal model (the tottering mouse) of episodic ataxia type 2. In a case series, chlorzoxazone, a non-selective activator of small-conductance calcium-activated potassium channels, was shown to reduce the DBN. The efficacy of acetyl-DL-leucine as a potential new symptomatic treatment for cerebellar diseases has been demonstrated in three case series. The ongoing randomized controlled trials on episodic ataxia type 2 (sustained-release form of 4-aminopyridine vs. acetazolamide vs. placebo; EAT2TREAT), vestibular migraine with metoprolol (PROVEMIG-trial), cerebellar gait disorders (sustained-release form of 4-aminopyridine vs. placebo; FACEG) and cerebellar ataxia (acetyl-DL-leucine vs. placebo; ALCAT) will provide new insights into the pharmacotherapy of cerebellar and central vestibular disorders. PMID:27083881

  4. A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas

    PubMed Central

    Beauchamp, Roberta L.; James, Marianne F.; DeSouza, Patrick A.; Wagh, Vilas; Zhao, Wen-Ning; Jordan, Justin T.; Stemmer-Rachamimov, Anat; Plotkin, Scott R.; Gusella, James F.; Haggarty, Stephen J.; Ramesh, Vijaya

    2015-01-01

    Meningiomas are the most common primary intracranial adult tumor. All Neurofibromatosis 2 (NF2)-associated meningiomas and ~60% of sporadic meningiomas show loss of NF2 tumor suppressor protein. There are no effective medical therapies for progressive and recurrent meningiomas. Our previous work demonstrated aberrant activation of mTORC1 signaling that led to ongoing clinical trials with rapamycin analogs for NF2 and sporadic meningioma patients. Here we performed a high-throughput kinome screen to identify kinases responsible for mTORC1 pathway activation in NF2-deficient meningioma cells. Among the emerging top candidates were the mTORC2-specific target serum/glucocorticoid-regulated kinase 1 (SGK1) and p21-activated kinase 1 (PAK1). In NF2-deficient meningioma cells, inhibition of SGK1 rescues mTORC1 activation, and SGK1 activation is sensitive to dual mTORC1/2 inhibitor AZD2014, but not to rapamycin. PAK1 inhibition also leads to attenuated mTORC1 but not mTORC2 signaling, suggesting that mTORC2/SGK1 and Rac1/PAK1 pathways are independently responsible for mTORC1 activation in NF2-deficient meningiomas. Using CRISPR-Cas9 genome editing, we generated isogenic human arachnoidal cell lines (ACs), the origin cell type for meningiomas, expressing or lacking NF2. NF2-null CRISPR ACs recapitulate the signaling of NF2-deficient meningioma cells. Interestingly, we observe increased SGK1 transcription and protein expression in NF2-CRISPR ACs and in primary NF2-negative meningioma lines. Moreover, we demonstrate that the dual mTORC1/mTORC2 inhibitor, AZD2014 is superior to rapamycin and PAK inhibitor FRAX597 in blocking proliferation of meningioma cells. Importantly, AZD2014 is currently in use in several clinical trials of cancer. Therefore, we believe that AZD2014 may provide therapeutic advantage over rapalogs for recurrent and progressive meningiomas. PMID:26219339

  5. A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas.

    PubMed

    Beauchamp, Roberta L; James, Marianne F; DeSouza, Patrick A; Wagh, Vilas; Zhao, Wen-Ning; Jordan, Justin T; Stemmer-Rachamimov, Anat; Plotkin, Scott R; Gusella, James F; Haggarty, Stephen J; Ramesh, Vijaya

    2015-07-10

    Meningiomas are the most common primary intracranial adult tumor. All Neurofibromatosis 2 (NF2)-associated meningiomas and ~60% of sporadic meningiomas show loss of NF2 tumor suppressor protein. There are no effective medical therapies for progressive and recurrent meningiomas. Our previous work demonstrated aberrant activation of mTORC1 signaling that led to ongoing clinical trials with rapamycin analogs for NF2 and sporadic meningioma patients. Here we performed a high-throughput kinome screen to identify kinases responsible for mTORC1 pathway activation in NF2-deficient meningioma cells. Among the emerging top candidates were the mTORC2-specific target serum/glucocorticoid-regulated kinase 1 (SGK1) and p21-activated kinase 1 (PAK1). In NF2-deficient meningioma cells, inhibition of SGK1 rescues mTORC1 activation, and SGK1 activation is sensitive to dual mTORC1/2 inhibitor AZD2014, but not to rapamycin. PAK1 inhibition also leads to attenuated mTORC1 but not mTORC2 signaling, suggesting that mTORC2/SGK1 and Rac1/PAK1 pathways are independently responsible for mTORC1 activation in NF2-deficient meningiomas. Using CRISPR-Cas9 genome editing, we generated isogenic human arachnoidal cell lines (ACs), the origin cell type for meningiomas, expressing or lacking NF2. NF2-null CRISPR ACs recapitulate the signaling of NF2-deficient meningioma cells. Interestingly, we observe increased SGK1 transcription and protein expression in NF2-CRISPR ACs and in primary NF2-negative meningioma lines. Moreover, we demonstrate that the dual mTORC1/mTORC2 inhibitor, AZD2014 is superior to rapamycin and PAK inhibitor FRAX597 in blocking proliferation of meningioma cells. Importantly, AZD2014 is currently in use in several clinical trials of cancer. Therefore, we believe that AZD2014 may provide therapeutic advantage over rapalogs for recurrent and progressive meningiomas. PMID:26219339

  6. Generation of Noninvasive, Quantifiable, Orthotopic Animal Models for NF2-Associated Schwannoma and Meningioma.

    PubMed

    Burns, Sarah S; Chang, Long-Sheng

    2016-01-01

    Schwannomas and meningiomas are nervous system tumors that can occur sporadically or in patients with neurofibromatosis type 2 (NF2). Mutations of the Neurofibromatosis 2 (NF2) gene are frequently observed in these tumors. Schwannomas and meningiomas cause significant morbidities, and an FDA-approved medical therapy is currently not available. The development of preclinical animal models that accurately capture the clinical characteristics of these tumors will facilitate the evaluation of novel therapeutic agents for the treatment of these tumors, ultimately leading to more productive clinical trials. Here, we describe the generation of luciferase-expressing NF2-deficient schwannoma and meningioma cells and the use of these cells to establish orthotopic tumor models in immunodeficient mice. The growth of these tumors and their response to treatment can be measured effectively by bioluminescence imaging (BLI) and confirmed by small-animal magnetic resonance imaging (MRI). These and other animal models, such as genetically-engineered models, should substantially advance the investigation of promising therapies for schwannomas and meningiomas. PMID:27259921

  7. The unilateral occipital transtentorial approach for pineal region meningiomas: a report of 15 cases.

    PubMed

    Qiu, Bo; Wang, Yong; Ou, Shaowu; Guo, Zongze; Wang, Yunjie

    2014-10-01

    In the current study, we reviewed and re-evaluated the experiences of microsurgical management for pineal region meningiomas via the unilateral occipital transtentorial approach (Poppen's approach). Clinical data were obtained on 15 meningiomas of the pineal region, which underwent microsurgery via unilateral Poppen's approach from March 2009 to June 2012. These patients were hospitalized in our department; their data were collected and analyzed retrospectively. The tumors were removed via the right Poppen's approach in 12 cases and left Poppen's approach in 3 cases, and intraoperative external ventricular drainage was performed for hydrocephalus in 3 cases. As a result, gross total resection was achieved in 11 cases, near total resection in 3 cases and subtotal resection in 1 case. All resected tumors were pathologically confirmed. The postoperative complications included two cases of homonymous hemianopia, and deteriorated Parinaud syndrome and diplopia in one case. Ten cases were followed up (range 1-4 years) and no death occurred. On the basis of the existing literature and our experiences, the unilateral Poppen's approach is appropriate for most meningiomas of the pineal region that are small or intermediate in size. However, gross total resection might be difficult via the unilateral Poppen's approach for large-sized meningiomas with much contralateral infratentorial extension due to limited exposure. For these cases, combined supra-infratentorial or bilateral Poppen's approaches are recommended. Preoperative or intraoperative external ventricular drainage can increase tumor exposure and improve microsurgical effects. PMID:24397496

  8. [Linear accelerator-based stereotactic radiation treatment of patients with medial middle fossa meningiomas].

    PubMed

    Golanov, A V; Cherekaev, V A; Serova, N K; Pronin, I N; Gorlachev, G E; Kotel'nikova, T M; Podoprigora, A E; Kudriavtseva, P A; Galkin, M V

    2010-01-01

    Medial middle fossa meningiomas are challenging for neurosurgical treatment. Invasion of cranial nerves and vessels leads to high risk of complications after removal of such meningiomas. Currently methods of conformal stereotactic radiation treatment are applied wider and wider for the discussed lesions. During a 3.5-year period 80 patients with medial middle fossa meningiomas were treated in Burdenko Moscow Neurosurgical Institute using linear accelerator "Novalis". In 31 case radiation treatment was preceded by surgical resection. In majority of patients symptoms included cranial nerve dysfunction: oculomotor disturbances in 62.5%, trigeminal impairment--in 37.5%, visual deficit--in 43.8%, facial nerve palsy--in 1.25%. 74 patients underwent radiotherapy with classical fractioning, 2--in hypofractionated mode and 4 received radiosurgery. In cases of classical fractioning mean marginal dose reached 46.3 Gy during 28-33 fractions, in hypofractioning (7 fractions)--31.5 Gy, in radiosurgery--16.25 Gy. Mean follow-up period was 18.4 months (6-42 months). Control of tumor growth was achieved in 97.5% of cases (78 patients): in 42 (52.5%) lesion shrinked, in 36 (45%) stabilization was observed. Clinical examination revealed improvement of visual function in 15 patients (18%) and deterioration in 2 (2.5%). No new neuropathies were found. Stereotactic radiation treatment is the method of choice for medial anterior and middle fossa meningiomas due to effective control of tumor progression and minimal rate of complications. PMID:20429360

  9. Postoperative posterior ischemic optic neuropathy (PION) following right pterional meningioma surgery

    PubMed Central

    Maramattom, Boby Varkey; Sundar, Shyam; Thomas, Dalvin; Panikar, Dilip

    2016-01-01

    Postoperative visual loss (POVL) is an unpredictable complication of nonocular surgeries. Posterior ischemic optic neuropathy (PION) is particularly feared in spinal surgeries in the prone position. We report a rare case of PION occurring after surgery for a pterional meningioma and discuss the various factors implicated in POVL.

  10. Postoperative posterior ischemic optic neuropathy (PION) following right pterional meningioma surgery.

    PubMed

    Maramattom, Boby Varkey; Sundar, Shyam; Thomas, Dalvin; Panikar, Dilip

    2016-01-01

    Postoperative visual loss (POVL) is an unpredictable complication of nonocular surgeries. Posterior ischemic optic neuropathy (PION) is particularly feared in spinal surgeries in the prone position. We report a rare case of PION occurring after surgery for a pterional meningioma and discuss the various factors implicated in POVL. PMID:27570391

  11. Dural-Based Cavernoma of the Posterior Cranial Fossa Mimicking a Meningioma: A Case Report

    PubMed Central

    Cruz, Aurora S; Jeyamohan, Shiveindra; Tubbs, R. Shane; Page, Jeni; Chamiraju, Parthasarathi; Tkachenko, Lara; Rostad, Steven; Newell, David W.

    2016-01-01

    Cavernous angiomas usually occur in the parenchyma of both the supra and infratentorial compartments. At times, they can both clinically and radiologically mimic other dural-based lesions. We present a case of a patient with chronic occipital headaches, initially thought to have a meningioma, but proven to be a cavernoma with histological analysis. PMID:27190725

  12. Glioblastoma occurring after radiation therapy for meningioma: case report and review of literature

    SciTech Connect

    Zuccarello, M.; Sawaya, R.; deCourten-Meyers, G.

    1986-07-01

    A 32-year-old man developed an intracranial glioblastoma multiforme 10 years after irradiation for an incompletely resected convexity meningioma. The association of these two tumors is exceedingly rare. Therefore, we propose that this is a case of radiation-induced glioma and review the evidence supporting this view.

  13. INI1 mutations in meningiomas at a potential hotspot in exon 9

    PubMed Central

    Schmitz, U; Mueller, W; Weber, M; Sévenet, N; Delattre, O; Deimling, A von

    2001-01-01

    Rhabdoid tumours have been shown to carry somatic mutations in the INI1 (SMARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for meningiomas, however most of these alterations are considered to be associated with mutations of the NF2 gene. We examined a series of 126 meningiomas for alterations in the INI1 gene. Four identical somatic mutations in exon 9 were detected resulting in an exchange of Arg to His in position 377 of INI1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot therefore appears to be an important target in the formation of a fraction of meningiomas. In addition, 4 novel polymorphisms of INI1 were characterized. Our data indicate that the INI1 is a second tumour suppressor gene on chromosome 22 that may be important for the genesis of meningiomas. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161377

  14. Seizures in supratentorial meningioma: a systematic review and meta-analysis.

    PubMed

    Englot, Dario J; Magill, Stephen T; Han, Seunggu J; Chang, Edward F; Berger, Mitchel S; McDermott, Michael W

    2016-06-01

    OBJECT Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life. METHODS The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses. RESULTS The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30-2.34); an absence of headache (OR 1.77, 95% CI 1.04-3.25); peritumoral edema (OR 7.48, 95% CI 6.13-9.47); and non-skull base location (OR 1.77, 95% CI 1.04-3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants. CONCLUSIONS Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does

  15. WHO grade II meningioma: a retrospective study for outcome and prognostic factor assessment.

    PubMed

    Champeaux, Charles; Wilson, Elena; Shieff, Colin; Khan, Akbar Ali; Thorne, Lewis

    2016-09-01

    To analyse the outcome of patients with WHO grade II meningioma and identify factors that may influence recurrence and survival. Between January 2007 and September 2015, a retrospective search identified 194 WHO grade II meningiomas at the National Hospital for Neurology and Neurosurgery, London. Survival methods were implemented. 31 patients (16 %) had a previous history of grade I meningioma. The patients underwent a total of 344 surgical resections and 43.3 % received radiotherapy. 55 patients (28.4 %) had been re-operated on for a WHO grade II meningioma relapse. Median follow-up was 4.4 years. At the end of the study, 75 patients (40.1 %) had no residual tumour on the last scan. Surgical recurrence free survival at 5 years was 71.6, 95 % CI [63.5, 80.8]. Secondary grade II meningioma (HR = 2.29, p = 0.010), and, Simpson resection grade 1, 2 and 3 vs. 4 and 5 (HR = 0.57, p = 0.050) were associated with the surgical recurrence-free survival. 32 died from meningioma (16.5 %). Overall survival probability at 5 years was 83.2, 95 % CI [76.6, 90.4]. Age at diagnosis (HR = 0.22, p < 0.001), WHO grade I meningioma progressing into grade II (HR = 3.2, p = 0.001), tumour location (HR = 0.19, p < 0.001), and mitosis count (HR = 0.36, p = 0.010) were independently associated with the overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of recurrence nor a longer overall survival (p = 0.310). In our series shorter survival correlated with older age, increased mitoses, progression from grade I to II and location. We were not able to demonstrate a significant improvement in any of the clinical outcomes after radiotherapy. PMID:27311726

  16. MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors.

    PubMed

    Abramovich, C M; Prayson, R A

    1998-12-01

    Predicting tumor behavior in meningiomas based on histology alone has been problematic. This study retrospectively compares histology and MIB-1 (cell proliferation marker) labeling indices (LI) in benign, aggressive, and malignant meningiomas. Six histological features, including mitoses, necrosis, loss of pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared in 90 meningiomas (Fisher's exact test). Tumors with two or more of the above features were designated as aggressive meningiomas. Malignant meningiomas were characterized by brain invasion or metastasis. The MIB-1 LIs (% positive tumor cell nuclei) were compared between the three groups (Kruskal-Wallis test, Wilcoxon two-sample test). Of the benign meningiomas (n=37; mean age, 54 years), 41% had one of the six histological features, with nuclear pleomorphism (n=10) being the most frequent. The aggressive tumors (n=29; mean age, 61 years) were characterized by nuclear pleomorphism (n=28), mitoses (n=20), necrosis (n=16), loss of pattern (n=16), prominent nucleoli (n=6), and hypervascularity/hemosiderin deposition (n=5). Malignant tumors (n=24; mean age, 59 years) were characterized by nuclear pleomorphism (n=22), mitoses (n=21), loss of pattern (n=21), necrosis (n=21), nucleoli (n=17), and hypervascularity/hemosiderin deposition (n=3). Significant differences were found between the aggressive and malignant groups with regard to loss of pattern, necrosis, and nucleoli (P=.0043, .011, and .00029, respectively). Mean MIB-1 LIs for the benign, aggressive, and malignant groups were 1.0% (range, 0 to 5.5%),5.5% (range, 0.1 to 32.5%), and 12.0% (range, 0.3 to 32.5%), respectively. Differences in the mean MIB-1 LI between groups were statistically significant, with P values of <.0001 (benign v aggressive) and .0012 (aggressive v malignant). Mean MIB-1 LIs for recurrent versus nonrecurrent tumors were 7.1% (range, 0 to 32.5%) versus 3.8% (range, 0 to 20.9%) (P=.32

  17. Lessons from surgical outcome for intracranial meningioma involving major venous sinus

    PubMed Central

    Han, Moon-Soo; Kim, Yeong-Jin; Moon, Kyung-Sub; Lee, Kyung-Hwa; Yang, Jung-In; Kang, Woo Dae; Lim, Sa-Hoe; Jang, Woo-Youl; Jung, Tae-Young; Kim, In-Young; Jung, Shin

    2016-01-01

    Abstract Intracranial meningiomas involving the major venous sinus (MVS) pose several complication risks upon performing radical resection. Some surgeons consider MVS invasion a contraindication for a complete resection of meningioma, and others suggest total resection followed by venous reconstruction. The aim of the study was to analyze our surgical results and discuss management strategy for intracranial meningiomas involving the MVS. Between 1993 and 2011, 107 patients with intracranial meningiomas involving MVS underwent surgery in our institution. Clinicoradiological features including pathological features and operative findings were retrospectively analyzed. Median follow-up duration was 60.2 months (range, 6.2–218.2 months). Distributions of tumor cases according to the involved sinus were as follows: 86% parasagittal, 10.3% tentorial, and 3.7% peritorcular. Simpson Grade I/II removal was achieved in 93 of 107 patients (87%). Partially or totally occluded MVS by their meningiomas (Sindou classification IV and V) was found in 39 patients (36%). Progression rate was 12% (13/107) and progression-free survival rates were 89%, 86%, and 80% at 5, 7, and 10 years, respectively. Sindou classification (IV/V) and Karnofsky performance status (KPS) score 6 month after the surgery (KPS < 90) were predictive factors for progression in our study (P = 0.044 and P = 0.001, respectively). The resection degree did not reach statistical significance (P = 0.484). Interestingly, there was no progression in patients that underwent radiation therapy or gamma knife radiosurgery for residual tumor. There were no perioperative deaths. Complication rate was 21% with brain swelling being the most common complication. There was no predictive factor for occurrence of postoperative complication in this study. In conclusion, complete tumor resection with sinus reconstruction did not significantly prevent tumor recurrence in intracranial meningioma involving MVS

  18. Lessons from surgical outcome for intracranial meningioma involving major venous sinus.

    PubMed

    Han, Moon-Soo; Kim, Yeong-Jin; Moon, Kyung-Sub; Lee, Kyung-Hwa; Yang, Jung-In; Kang, Woo Dae; Lim, Sa-Hoe; Jang, Woo-Youl; Jung, Tae-Young; Kim, In-Young; Jung, Shin

    2016-08-01

    Intracranial meningiomas involving the major venous sinus (MVS) pose several complication risks upon performing radical resection. Some surgeons consider MVS invasion a contraindication for a complete resection of meningioma, and others suggest total resection followed by venous reconstruction. The aim of the study was to analyze our surgical results and discuss management strategy for intracranial meningiomas involving the MVS. Between 1993 and 2011, 107 patients with intracranial meningiomas involving MVS underwent surgery in our institution. Clinicoradiological features including pathological features and operative findings were retrospectively analyzed. Median follow-up duration was 60.2 months (range, 6.2-218.2 months). Distributions of tumor cases according to the involved sinus were as follows: 86% parasagittal, 10.3% tentorial, and 3.7% peritorcular. Simpson Grade I/II removal was achieved in 93 of 107 patients (87%). Partially or totally occluded MVS by their meningiomas (Sindou classification IV and V) was found in 39 patients (36%). Progression rate was 12% (13/107) and progression-free survival rates were 89%, 86%, and 80% at 5, 7, and 10 years, respectively. Sindou classification (IV/V) and Karnofsky performance status (KPS) score 6 month after the surgery (KPS < 90) were predictive factors for progression in our study (P = 0.044 and P = 0.001, respectively). The resection degree did not reach statistical significance (P = 0.484). Interestingly, there was no progression in patients that underwent radiation therapy or gamma knife radiosurgery for residual tumor. There were no perioperative deaths. Complication rate was 21% with brain swelling being the most common complication. There was no predictive factor for occurrence of postoperative complication in this study. In conclusion, complete tumor resection with sinus reconstruction did not significantly prevent tumor recurrence in intracranial meningioma involving MVS. Considering the

  19. Variant PTA Terminating in Cerebellar Artery, Associated with Multiple Aneurysms

    PubMed Central

    Hwang, Yeong Uk

    2016-01-01

    Persistent trigeminal artery (PTA) is one of the remnant fetal anastomoses between the carotid artery and basilar artery. PTAs are classified according to angiographic appearance and various connection. Among them, those directly terminating in the cerebellar arteries are rare subtype. In addition, aneurysms of the PTA are unusual in the literature and have not previously accompanied this subtype of PTA connecting cerebellar artery. We present the first case of an aneurysm of the PTA which is directly terminating in the cerebellar arteries and combined with multiple aneurysms. PMID:27446623

  20. Variant PTA Terminating in Cerebellar Artery, Associated with Multiple Aneurysms.

    PubMed

    Hwang, Yeong Uk; Kim, Jin Woo

    2016-01-01

    Persistent trigeminal artery (PTA) is one of the remnant fetal anastomoses between the carotid artery and basilar artery. PTAs are classified according to angiographic appearance and various connection. Among them, those directly terminating in the cerebellar arteries are rare subtype. In addition, aneurysms of the PTA are unusual in the literature and have not previously accompanied this subtype of PTA connecting cerebellar artery. We present the first case of an aneurysm of the PTA which is directly terminating in the cerebellar arteries and combined with multiple aneurysms. PMID:27446623

  1. Ferumoxytol-enhanced MRI differentiation of meningioma from dural metastases: a pilot study with immunohistochemical observations.

    PubMed

    Hamilton, Bronwyn E; Woltjer, Randall L; Prola-Netto, Joao; Nesbit, Gary M; Gahramanov, Seymur; Pham, Thao; Wagner, Jaime; Neuwelt, Edward A

    2016-09-01

    Malignant dural neoplasms are not reliably distinguished from benign dural neoplasms with contrast-enhanced magnetic resonance imaging (MRI). MRI enhancement in central nervous system (CNS) diseases imaged with ferumoxytol has been attributed to intracellular uptake in macrophages rather than vascular leakage. We compared imaging to histopathology and immunohistochemistry in meningiomas and dural metastases having ferumoxytol-enhanced MRI (FeMRI) and gadolinium-enhanced MRI (GdMRI) in order to correlate enhancement patterns to macrophage presence and vascular state. All patients having extraaxial CNS tumors were retrospectively selected from one of two ongoing FeMRI studies. Enhancement was compared between GdMRI and FeMRI. Diagnoses were confirmed histologically and/or by characteristic imaging. Tumor and vascular histology was reviewed. Immunohistochemical staining for CD68 (a macrophage marker), Connexin-43 (Cx43) (a marker of normal gap junctions), and smooth muscle actin (SMA) as a marker of vascularity, was performed in seven study cases with available tissue. Immunohistochemistry was performed on archival material from 33 subjects outside of the current study as controls: 20 WHO grade I cases of meningioma and 13 metastatic tumors. Metastases displayed marked delayed enhancement on FeMRI, similar to GdMRI. Four patients with dural metastases and one patient with meningioma showed similar enhancement on FeMRI and GdMRI. Five meningiomas with typical enhancement on GdMRI lacked enhancement on FeMRI. Enhancement on FeMRI was better associated with decreased Cx43 expression than intralesional macrophages. These pilot data suggest that FeMRI may better differentiate metastatic disease from meningiomas than GdMRI, and that differences in tumor vasculature rather than macrophage presence could underlie differences in contrast enhancement. PMID:27393348

  2. 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

    PubMed Central

    Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

    2014-01-01

    BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

  3. Intracranial meningiomas: Prognostic factors and treatment outcome in patients undergoing postoperative radiation therapy

    PubMed Central

    Anvari, Kazem; Hosseini, Sare; Rahighi, Saeid; Toussi, Mehdi Seilanian; Roshani, Nasrin; Torabi-Nami, Mohammad

    2016-01-01

    Background: Meningioma constitutes 20% of the intracranial neoplasms. Followed by surgery as the primary treatment for most patients, radiotherapy becomes indicated in high-grade tumors with incomplete surgical removal. We evaluated the prognostic factors and overall outcome in meningioma patients who underwent radiotherapy. Materials and Methods: In this retrospective analysis, data from all patients with documented diagnosis of meningioma who referred to the Omid and Ghaem Oncology Centers (Mashhad, Iran) from 2002 to 2013 were included. We calculated the overall survival rates using the Kaplan–Meier method and compared the survival curves between groups by the log-rank test. Results: Eighty-three patients with a median age of 50 years (ranging: 16–84) were included. Grade I, II, and III meningiomas were seen in 40 (48%), 31 (37%), and 12 (15%) patients, respectively. Radiation therapy was indicated due to tumor recurrence, incomplete excision, or tumor grade in 32, 8, and 43 patients, respectively. Tumor grade had a significant effect on the overall survival with a 3-year overall survival of 76.7%, 43.5%, and 13.3% in Grade I, II, and III, respectively (P < 0.001). Gender, age, and tumor location were not correlated with the overall survival. Moreover, patients with Grade II and III who underwent total resection had a significantly higher overall survival than those with subtotal resection or biopsy alone (5-year survival rates of 82% vs. 17.1%, respectively; P = 0.008). Conclusion: Tumor grade was the most important prognostic factor in meningioma patients undergoing radiation therapy. In patients with Grade II and III tumors, the extent of surgical resection is significantly correlated with the overall survival. PMID:27274498

  4. Effects of intracranial meningioma location, size, and surgery on neurocognitive functions: a 3-year prospective study.

    PubMed

    Liouta, Evangelia; Koutsarnakis, Christos; Liakos, Faidon; Stranjalis, George

    2016-06-01

    OBJECT Current recommendations stress the need for cognitive parameters to be integrated in the evaluation of outcomes for intracranial meningioma surgery. The aim of this prospective study was to examine neurocognitive function in meningioma patients pre- and postoperatively. METHODS Patients with skull base (anterior and middle fossa) and convexity (anterior and posterior) meningiomas (n = 54) underwent neuropsychological examination prior to and 1 year after surgery. A control group (n = 52) of healthy volunteers matched for age, sex, and education underwent the same examination. Assessments included executive, memory, and motor functions with standardized testing. Patients with convexity meningiomas were clinically assessed for parietal association cortex functions. RESULTS All patients performed significantly worse (p < 0.05) in most neurocognitive domains than controls. The skull base group showed more disturbances in memory than the convexity group (p < 0.05). The anterior convexity group showed more deficits in executive function than the posterior convexity group, which presented with parietal association cortex deficits. Verbal deficits were more pronounced in the left hemisphere than in the right hemisphere. Patients with a large tumor (> 4 cm) had more severe neurocognitive deficits than those with a small tumor (< 4 cm). Postoperatively, patients showed no deterioration in neurocognitive function. Instead, significant improvement (p < 0.05) was observed in some executive, motor, and parietal association cortex functions. CONCLUSIONS According to the authors' findings, intracranial meningiomas may cause neurocognitive deficits in patients. Surgery does not cause a deterioration in cognitive function; instead, it may lead to improvements in some functions. Permanent neuropsychological postoperative deficits should be interpreted as tumor-induced rather than due to surgery. PMID:26636380

  5. Hereditary Cerebellar Ataxias: A Korean Perspective

    PubMed Central

    Kim, Ji Sun; Cho, Jin Whan

    2015-01-01

    Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes. PMID:26090078

  6. Cucurbitacin I blocks cerebrospinal fluid and platelet derived growth factor-BB stimulation of leptomeningeal and meningioma DNA synthesis

    PubMed Central

    2013-01-01

    Background Currently, there are no consistently effective chemotherapies for recurrent and inoperable meningiomas. Recently, cucurbitacin I (JSI-124), a naturally occurring tetracyclic triterpenoid compound used as folk medicines has been found to have cytoxic and anti-proliferative properties in several malignancies thru inhibition of activator of transcription (STAT3) activation. Previously, we have found STAT3 to be activated in meningiomas, particularly higher grade tumors. Methods Primary leptomeningeal cultures were established from 17, 20 and 22 week human fetuses and meningioma cell cultures were established from 6 World Health Organization (WHO) grade I or II meningiomas. Cells were treated with cerebrospinal fluid from patients without neurologic disease. The effects of cucurbitacin I on cerebrospinal fluid stimulation of meningioma cell DNA synthesis phosphorylation/activation of JAK1, STAT3, pMEK1/2, p44/42MAPK, Akt, mTOR, Rb and caspase 3 activation were analyzed in human leptomeningeal and meningioma cells. Results Cerebrospinal fluid significantly stimulated DNA synthesis in leptomeningeal cells. Co-administration of cucurbitacin I (250 nM) produces a significant blockade of this effect. Cucurbitacin I alone also produced a significant reduction in basal DNA synthesis. In grade I and II meningiomas, cerebrospinal fluid also significantly stimulated DNA synthesis. Co-administration of cucurbitacin I (250 nM) blocked this effect. In the leptomeningeal cultures, cerebrospinal fluid stimulated STAT3 phosphorylation but not p44/42MAPK, Akt or mTOR. Cucurbitacin I had no effect on basal STAT3 phosphorylation but co-administration with cerebrospinal fluid blocked cerebrospinal fluid stimulation of STAT3 phosphorylation in each. In the grade I meningiomas, cerebrospinal fluid stimulated phosphorylation of STAT3 and decreased MEK1/2 and cucurbitacin I had no effect on basal STAT3, p44/42MAPK, Akt, JAK1, mTOR, or Rb phosphorylation. In the grade II

  7. Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia

    PubMed Central

    Yang, Yang; Chen, Bao-Guo; Zhang, Yi-Wei; Bi, Hong-Yan

    2016-01-01

    The cerebellar deficit hypothesis for developmental dyslexia claims that cerebellar dysfunction causes the failures in the acquisition of visuomotor skills and automatic reading and writing skills. In people with dyslexia in the alphabetic languages, the abnormal activation and structure of the right or bilateral cerebellar lobes have been identified. Using a typical implicit motor learning task, however, one neuroimaging study demonstrated the left cerebellar dysfunction in Chinese children with dyslexia. In the present study, using voxel-based morphometry, we found decreased gray matter volume in the left cerebellum in Chinese children with dyslexia relative to age-matched controls. The positive correlation between reading performance and regional gray matter volume suggests that the abnormal structure in the left cerebellum is responsible for reading disability in Chinese children with dyslexia. PMID:27047403

  8. Cerebellar transcranial direct current stimulation in neurological disease.

    PubMed

    Ferrucci, Roberta; Bocci, Tommaso; Cortese, Francesca; Ruggiero, Fabiana; Priori, Alberto

    2016-01-01

    Several studies have highlighted the therapeutic potential of transcranial direct current stimulation (tDCS) in patients with neurological diseases, including dementia, epilepsy, post-stroke dysfunctions, movement disorders, and other pathological conditions. Because of this technique's ability to modify cerebellar excitability without significant side effects, cerebellar tDCS is a new, interesting, and powerful tool to induce plastic modifications in the cerebellum. In this report, we review a number of interesting studies on the application of cerebellar tDCS for various neurological conditions (ataxia, Parkinson's disease, dystonia, essential tremor) and the possible mechanism by which the stimulation acts on the cerebellum. Study findings indicate that cerebellar tDCS is a promising therapeutic tool in treating several neurological disorders; however, this method's efficacy appears to be limited, given the current data. PMID:27595007

  9. Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia.

    PubMed

    Yang, Ying-Hui; Yang, Yang; Chen, Bao-Guo; Zhang, Yi-Wei; Bi, Hong-Yan

    2016-01-01

    The cerebellar deficit hypothesis for developmental dyslexia claims that cerebellar dysfunction causes the failures in the acquisition of visuomotor skills and automatic reading and writing skills. In people with dyslexia in the alphabetic languages, the abnormal activation and structure of the right or bilateral cerebellar lobes have been identified. Using a typical implicit motor learning task, however, one neuroimaging study demonstrated the left cerebellar dysfunction in Chinese children with dyslexia. In the present study, using voxel-based morphometry, we found decreased gray matter volume in the left cerebellum in Chinese children with dyslexia relative to age-matched controls. The positive correlation between reading performance and regional gray matter volume suggests that the abnormal structure in the left cerebellum is responsible for reading disability in Chinese children with dyslexia. PMID:27047403

  10. Novel Approaches to Studying the Genetic Basis of Cerebellar Development

    PubMed Central

    Sajan, Samin A.; Waimey, Kathryn E.

    2010-01-01

    The list of genes that when mutated cause disruptions in cerebellar development is rapidly increasing. The study of both spontaneous and engineered mouse mutants has been essential to this progress, as it has revealed much of our current understanding of the developmental processes required to construct the mature cerebellum. Improvements in brain imaging, such as magnetic resonance imaging (MRI) and the emergence of better classification schemes for human cerebellar malformations, have recently led to the identification of a number of genes which cause human cerebellar disorders. In this review we argue that synergistic approaches combining classical molecular techniques, genomics, and mouse models of human malformations will be essential to fuel additional discoveries of cerebellar developmental genes and mechanisms. PMID:20387026

  11. Malignant cerebellar peduncle lesions - rapid progression and poor outcome

    PubMed Central

    Singla, Navneet; Kapoor, Ankur; Savardekar, Amey; Radotra, B. D.; Chatterjee, Debjyoti; Gupta, Sunil K.

    2016-01-01

    Background: Tumors arising from cerebellar peduncle are extremely rare and behave aggressively. The inclusion of these into either cerebellar or brainstem gliomas is contentious. Case Description: We performed clinicopathological review of three patients treated at our institute and surveyed the literature for previous such reported cases. Mean duration of symptoms in our patients was 2 weeks. Subtotal tumor resection was performed in two patients while the third underwent stereotactic biopsy followed by chemoradiotherapy. Histopathology revealed glioblastoma in initial two patients and medulloblastoma Grade IV in the third. The two patients who underwent surgical excision succumbed to the illness within 2 days and a month, respectively. Conclusion: Malignant cerebellar peduncular lesions have poor overall survival despite surgical debulking. It is not confirmed whether these tumors should be considered as cerebellar lesions or brainstem gliomas due to aggressive clinical behavior, and so the ideal line of management is not yet known. PMID:27057396

  12. The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review.

    PubMed

    Motekallemi, Arash; Jeltema, Hanne-Rinck; Metzemaekers, Jan D M; van Dam, Gooitzen M; Crane, Lucy M A; Groen, Rob J M

    2015-10-01

    Meningiomas are the second most common primary tumors affecting the central nervous system. Surgical treatment can be curative in case of complete resection. 5-aminolevulinic acid (5-ALA) has been established as an intraoperative tool in malignant glioma surgery. A number of studies have tried to outline the merits of 5-ALA for the resection of intracranial meningiomas. In the present paper, we review the existing literature about the application of 5-ALA as an intraoperative tool for the resection of intracranial meningiomas. PubMed was used as the database for search tasks. We included articles published in English without limitations regarding publication date. Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study. PMID:25736455

  13. Esophoria or esotropia in adulthood: a sign of cerebellar dysfunction?

    PubMed

    Hüfner, Katharina; Frenzel, Claudia; Kremmyda, Olympia; Adrion, Christine; Bardins, Stanislavs; Glasauer, Stefan; Brandt, Thomas; Strupp, Michael

    2015-03-01

    Convergent strabismus is a common diagnosis in early childhood, when it is mostly considered benign. If it develops later in life, strabismus can, however, be a sign of neurological disease. In these cases the underlying pathophysiological mechanisms are largely unknown. In this retrospective case-control study we analyzed the neuro-ophthalmological examination reports of 400 adult patients who presented at the German Center for Vertigo and Balance Disorders to determine an association between ocular misalignment and cerebellar dysfunction. Patients with cerebellar signs (i.e., cerebellar ataxia and/or cerebellar ocular motor signs) had a 4.49 (95 % CI [1.60; 13.78]) times higher frequency of ocular misalignment and specifically a 13.3 (95 % CI [3.80; 55.73]) times increased frequency of esophoria/esotropia (ESO) during distant gaze than patients without cerebellar dysfunction. ESO when looking into the distance was associated with saccadic smooth pursuit, dysmetria of saccades, and downbeat nystagmus (DBN) (χ (2) test, p < 0.0001 for all associations). Patients with cerebellar dysfunction also showed mildly impaired eye abduction (χ (2) test, left eye and right eye: p < 0.0001), associated with horizontal gaze-evoked nystagmus (χ (2) test, p < 0.0001). The association of ESO and DBN implicates a pathophysiological involvement of the cerebellar flocculus, while the association with dysmetric saccades suggests involvement of the oculomotor vermis. This is compatible with animal studies showing that the pathways of the flocculus/posterior interposed nucleus and vermis/nucleus fastigii are both involved in vergence movements and static binocular alignment. From a clinical point of view, a newly diagnosed esophoria/esotropia only during distant gaze may be a sign of a cerebellar disease. PMID:25522697

  14. Cerebellar contributions to neurological soft signs in healthy young adults.

    PubMed

    Hirjak, Dusan; Thomann, Philipp A; Kubera, Katharina M; Stieltjes, Bram; Wolf, Robert C

    2016-02-01

    Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin, e.g., in patients with schizophrenia and autism. Yet NSS are also present in healthy individuals suggesting a neurodevelopmental signature of motor function, probably as a continuum between health and disease. So far, little is known about the neural mechanisms underlying these motor phenomena in healthy persons, and it is even less known whether the cerebellum contributes to NSS expression. Thirty-seven healthy young adults (mean age = 23 years) were studied using high-resolution structural magnetic resonance imaging (MRI) and "resting-state" functional MRI at three Tesla. NSS levels were measured using the "Heidelberg Scale." Cerebellar gray matter volume was investigated using cerebellum-optimized voxel-based analysis methods. Cerebellar function was assessed using regional homogeneity (ReHo), a measure of local network strength. The relationship between cerebellar structure and function and NSS was analyzed using regression models. There was no significant relationship between cerebellar volume and NSS (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). Positive associations with cerebellar lobule VI activity were found for the "motor coordination" and "hard signs" NSS domains. A negative relationship was found between lobule VI activity and "complex motor task" domain (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). The data indicate that in healthy young adults, distinct NSS domains are related to cerebellar activity, specifically with activity of cerebellar subregions with known cortical somatomotor projections. In contrast, cerebellar volume is not predictive of NSS in healthy persons. PMID:25708455

  15. Primary cerebellar agenesis presenting as isolated cognitive impairment

    PubMed Central

    Ashraf, Obaid; Jabeen, Shumyla; Khan, Azhar; Shaheen, Feroze

    2016-01-01

    Primary cerebellar agenesis is a rare entity. To the best of our knowledge, eleven living cases have been reported till date. Most of these were associated with some degree of motor impairment. We present a case of cerebellar agenesis in a child who presented with cognitive abnormalities leading to poor performance at school. No motor impairment was seen. Among the eleven cases reported earlier, only one case showed lack of motor impairment.

  16. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    PubMed

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration. PMID:26155762

  17. Emotions and their cognitive control in children with cerebellar tumors.

    PubMed

    Hopyan, Talar; Laughlin, Suzanne; Dennis, Maureen

    2010-11-01

    A constellation of deficits, termed the cerebellar cognitive affective syndrome (CCAS), has been reported following acquired cerebellar lesions. We studied emotion identification and the cognitive control of emotion in children treated for acquired tumors of the cerebellum. Participants were 37 children (7-16 years) treated for cerebellar tumors (19 benign astrocytomas (AST), 18 malignant medulloblastomas (MB), and 37 matched controls (CON). The Emotion Identification Task investigated recognition of happy and sad emotions in music. In two cognitive control tasks, we investigated whether children could identify emotion in situations in which the emotion in the music and the emotion in the lyrics was either congruent or incongruent. Children with cerebellar tumors identified emotion as accurately and quickly as controls (p > .05), although there was a significant interaction of emotions and group (p < .01), with the MB group performing less accurately identifying sad emotions, and both cerebellar tumor groups were impaired in the cognitive control of emotions (p < .01). The fact that childhood acquired cerebellar tumors disrupt cognitive control of emotion rather than emotion identification provides some support for a model of the CCAS as a disorder, not so much of emotion as of the regulation of emotion by cognition. PMID:20887648

  18. Disrupted cortico-cerebellar connectivity in older adults

    PubMed Central

    Bernard, Jessica A.; Peltier, Scott J.; Wiggins, Jillian Lee; Jaeggi, Susanne M.; Buschkuehl, Martin; Fling, Brett W.; Kwak, Youngbin; Jonides, John; Monk, Christopher S.; Seidler, Rachael D.

    2013-01-01

    Healthy aging is marked by declines in a variety of cognitive and motor abilities. A better understanding of the aging brain may aid in elucidating the neural substrates of these behavioral effects. Investigations of resting state functional brain connectivity have provided insights into pathology, and to some degree, healthy aging. Given the role of the cerebellum in both motor and cognitive behaviors, as well as its known volumetric declines with age, investigating cerebellar networks may shed light on the neural bases of age-related functional declines. We mapped the resting state networks of the lobules of the right hemisphere and the vermis of the cerebellum in a group of healthy older adults and compared them to those of young adults. We report disrupted cortico-cerebellar resting state network connectivity in older adults. These results remain even when controlling for cerebellar volume, signal-to-noise ratio, and signal-to-fluctuation noise ratio. Specifically, there was consistent disruption of cerebellar connectivity with both the striatum and the medial temporal lobe. Associations between connectivity strength and both sensorimotor and cognitive task performance indicate that cerebellar engagement with the default mode network and striatal pathways is associated with better performance for older adults. These results extend our understanding of the resting state networks of the aging brain to include cortico-cerebellar networks, and indicate that age differences in network connectivity strength are important for behavior. PMID:23792980

  19. Verbal memory impairments in children after cerebellar tumor resection

    PubMed Central

    Kirschen, Matthew P.; Davis-Ratner, Mathew S.; Milner, Marnee W.; Annabel Chen, S.H.; Schraedley-Desmond, Pam; Fisher, Paul G.; Desmond, John E.

    2009-01-01

    This study was designed to investigate cerebellar lobular contributions to specific cognitive deficits observed after cerebellar tumor resection. Verbal working memory (VWM) tasks were administered to children following surgical resection of cerebellar pilocytic astrocytomas and age-matched controls. Anatomical MRI scans were used to quantify the extent of cerebellar lobular damage from each patient’s resection. Patients exhibited significantly reduced digit span for auditory but not visual stimuli, relative to controls, and damage to left hemispheral lobule VIII was significantly correlated with this deficit. Patients also showed reduced effects of articulatory suppression and this was correlated with damage to the vermis and hemispheral lobule IV/V bilaterally. Phonological similarity and recency effects did not differ overall between patients and controls, but outlier patients with abnormal phonological similarity effects to either auditory or visual stimuli were found to have damage to hemispheral lobule VIII/VIIB on the left and right, respectively. We postulate that damage to left hemispheral lobule VIII may interfere with encoding of auditory stimuli into the phonological store. These data corroborate neuroimaging studies showing focal cerebellar activation during VWM paradigms, and thereby allow us to predict with greater accuracy which specific neurocognitive processes will be affected by a cerebellar tumor resection. PMID:19491473

  20. Oxidative injury in multiple sclerosis cerebellar grey matter.

    PubMed

    Kemp, Kevin; Redondo, Juliana; Hares, Kelly; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2016-07-01

    Cerebellar dysfunction is a significant contributor to disability in multiple sclerosis (MS). Both white matter (WM) and grey matter (GM) injury occurs within MS cerebellum and, within GM, demyelination, inflammatory cell infiltration and neuronal injury contribute to on-going pathology. The precise nature of cerebellar GM injury is, however, unknown. Oxidative stress pathways with ultimate lipid peroxidation and cell membrane injury occur extensively in MS and the purpose of this study was to investigate these processes in MS cerebellar GM. Post-mortem human cerebellar GM from MS and control subjects was analysed immunohistochemically, followed by semi-quantitative analysis of markers of cellular injury, lipid peroxidation and anti-oxidant enzyme expression. We have shown evidence for reduction in myelin and neuronal markers in MS GM, coupled to an increase in expression of a microglial marker. We also show that the lipid peroxidation product 4-hydroxynonenal co-localises with myelin and its levels negatively correlate to myelin basic protein levels. Furthermore, superoxide dismutase (SOD1 and 2) enzymes, localised within cerebellar neurons, are up-regulated, yet the activation of subsequent enzymes responsible for the detoxification of hydrogen peroxide, catalase and glutathione peroxidase are relatively deficient. These studies provide evidence for oxidative injury in MS cerebellar GM and further help define disease mechanisms within the MS brain. PMID:27086975

  1. Voltage-gated calcium channel autoimmune cerebellar degeneration

    PubMed Central

    McKasson, Marilyn; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Carlson, Noel; Bromberg, Mark; Greenlee, John E.

    2016-01-01

    Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. Results: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. Conclusions: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early. PMID:27088118

  2. Cell-mediated immune response of patients with meningiomas defined in vitro by a [3H]proline microcytotoxicity test.

    PubMed Central

    Pees, H W; Seidel, B

    1976-01-01

    Cell-mediated cytotoxicity (CTX) of meningioma patients was assessed postoperatively by a [3H]proline microcytotoxicity test. Autologous and allogeneic tumour cells were used for prelabelling with isotope and peripheral blood lymphocytes added in a ratio of 200:1. After 60 hg the plates were washed and residual CMP counted. Control target cells consisted of normal skin fibroblasts. CTX was calculated in percentage reduction compared to cultures incubated with control lymphocytes. Specific CTX on meningioma cells (i.e. not destroying control cells) greater than 20% was considered 'positive' if significant at P less than 0-05. Fifteen of twenty-three meningiomas showed specific CTX (65%). Among eight CNS tumours of different type and thirteen non-malignant diseases and normals only three (14%) were specifically cytotoxic for meningioma cells. A cross-reaction could be demonstrated between autologous and allogeneic meningioma target cells. However, no activity of lymphocytes from patients with meningiomas on glioblastoma cells and foetal brain tissue could be found at the ratio used for evaluation. Evidence is presented indicating that a cellular immune response as measured in the microcytotoxic test may be dependent on a residual or recurrent tumour in the body. PMID:1277580

  3. A nationwide cohort study on the incidence of meningioma in women using postmenopausal hormone therapy in Finland.

    PubMed

    Korhonen, Katariina; Auvinen, Anssi; Lyytinen, Heli; Ylikorkala, Olavi; Pukkala, Eero

    2012-02-15

    The authors conducted a nationwide cohort study to evaluate the association between postmenopausal hormone therapy and meningioma incidence in Finland. All women who had used hormone therapy at least for 6 months at the age of 50 years or older during 1994-2009 were included. Women who had used postmenopausal hormone therapy were identified from the medical reimbursement register of the Social Insurance Institution (131,480 estradiol users and 131,248 estradiol-progestin users), and meningioma cases were identified from the Finnish Cancer Registry. During the average 9 years of follow-up, 289 estradiol users and 196 estradiol-progestin users were diagnosed with meningioma. Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P < 0.001) than in the background population. In contrast, this risk was not increased in users of combination therapy (standardized incidence ratio = 0.93, 95% confidence interval: 0.80, 1.06). There was no difference in risk between continuous and sequential use of hormone therapy. Estradiol-only therapy was accompanied with a slightly increased risk of meningioma. PMID:22287638

  4. Identification of a third Protein 4.1 tumor suppressor, Protein 4.1R, in meningioma pathogenesis.

    PubMed

    Robb, Victoria A; Li, Wen; Gascard, Philippe; Perry, Arie; Mohandas, Narla; Gutmann, David H

    2003-08-01

    Meningiomas are common central nervous system tumors; however, the mechanisms underlying their pathogenesis are largely undefined. In this report, we demonstrate that a third Protein 4.1 family member, Protein 4.1R, functions as a meningioma tumor suppressor. We observed loss of Protein 4.1R expression in two meningioma cell lines (IOMM-Lee, CH157-MN) by Western blotting as well as in 6 of 15 sporadic meningiomas by immunohistochemistry and fluorescence in situ hybridization. In support of a meningioma tumor suppressor function, Protein 4.1R overexpression resulted in reduced IOMM-Lee and CH157-MN cell proliferation. Similar to the Protein 4.1B and merlin tumor suppressors, Protein 4.1R membrane localization increased significantly under conditions of growth arrest in vitro. Lastly, we show that Protein 4.1R interacted with a subset of merlin/Protein 4.1B interactors including CD44 and betaII-spectrin. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor in the molecular pathogenesis of meningioma. PMID:12901833

  5. HMGN5 blockade by siRNA enhances apoptosis, suppresses invasion and increases chemosensitivity to temozolomide in meningiomas.

    PubMed

    He, Jing; Liu, Chaoyang; Wang, Bin; Li, Na; Zuo, Guoqin; Gao, Dewei

    2015-10-01

    The high-mobility group nucleosome-binding protein-5 (HMGN5) is frequently overexpressed in various malignant cancers. However, the potential correlation between HMGN5 and prognosis in patients with meningiomas remains unknown. In the present study, we explored the expression of HMGN5 in meningiomas with immunohistochemistry and correlated the results to the patient outcome. Potential effects of HMGN5 on tumor growth, apoptosis and invasion were also examined in representative cell lines (IOMM-Lee and CH157) by downregulating HMGN5 with RNA interference (siRNA). We demonstrate that there is a positive association between HMGN5 expression and meningioma histological grade. Statistical analysis reveals that lower HMGN5 expression predict lower meningioma recurrence. In addition, downregulation of HMGN5 inhibits IOMM-Lee and CH157 cell proliferation, enhances cell apoptosis and suppresses tumor invasion. Our results further revealed that HMGN5 inhibition decreased P-glycoprotein (MDR-1) expression without affecting multidrug resistance associated proteins 1 (MRP-1) expression to increase chemosensitivity to temozolomide (TMZ) of meningioma cells. Collectively, this study indicates that HMGN5 is a novel target for developing effective therapeutic strategies for malignant meningiomas. PMID:26315299

  6. Altered cerebellar connectivity in Parkinson's patients ON and OFF L-DOPA medication

    PubMed Central

    Festini, Sara B.; Bernard, Jessica A.; Kwak, Youngbin; Peltier, Scott; Bohnen, Nicolaas I.; Müller, Martijn L. T. M.; Dayalu, Praveen; Seidler, Rachael D.

    2015-01-01

    Although nigrostriatal changes are most commonly affiliated with Parkinson's disease, the role of the cerebellum in Parkinson's has become increasingly apparent. The present study used lobule-based cerebellar resting state functional connectivity to (1) compare cerebellar-whole brain and cerebellar-cerebellar connectivity in Parkinson's patients both ON and OFF L-DOPA medication and controls, and to (2) relate variations in cerebellar connectivity to behavioral performance. Results indicated that, when contrasted to the control group, Parkinson's patients OFF medication had increased levels of cerebellar-whole brain and cerebellar-cerebellar connectivity, whereas Parkinson's patients ON medication had decreased levels of cerebellar-whole brain and cerebellar-cerebellar connectivity. Moreover, analyses relating levels of cerebellar connectivity to behavioral measures demonstrated that, within each group, increased levels of connectivity were most often associated with improved cognitive and motor performance, but there were several instances where increased connectivity was related to poorer performance. Overall, the present study found medication-variant cerebellar connectivity in Parkinson's patients, further demonstrating cerebellar changes associated with Parkinson's disease and the moderating effects of medication. PMID:25954184

  7. Post-Plasmodium vivax malaria cerebellar ataxia and optic neuritis: A new form of delayed cerebellar ataxia or cerebellar variant of acute disseminated encephalomyelitis?

    PubMed Central

    Kasundra, Gaurav M.; Bhargava, Amita Narendra; Bhushan, Bharat; Shubhakaran, Khichar; Sood, Isha

    2015-01-01

    Acute disseminated encephalomyelitis (ADEM) is commonly seen after viral and bacterial infections, immunization, and Plasmodium falciparum (PF) malaria. Plasmodium vivax (PV) rarely causes ADEM. We report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from PV. Magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of ADEM. No specific viral etiology was found on cerebrospinal fluid examination. Patient responded well to treatment without any sequelae. Thus, PV too is an important cause of ADEM along with PF. Two of the previously reported cases had co-infection with falciparum malaria. The only other two reported cases, as also this patient, are from Asia. A geographical or racial predisposition needs to be evaluated. Also, a possibility of post-PV delayed cerebellar ataxia, which is classically described post-PF infection, may be considered as it may be clinically, radiologically, and prognostically indistinguishable from a milder presentation of ADEM. PMID:25878748

  8. PDGF activation in PGDS-positive arachnoid cells induces meningioma formation in mice promoting tumor progression in combination with Nf2 and Cdkn2ab loss.

    PubMed

    Peyre, Matthieu; Salaud, Céline; Clermont-Taranchon, Estelle; Niwa-Kawakita, Michiko; Goutagny, Stephane; Mawrin, Christian; Giovannini, Marco; Kalamarides, Michel

    2015-10-20

    The role of PDGF-B and its receptor in meningeal tumorigenesis is not clear. We investigated the role of PDGF-B in mouse meningioma development by generating autocrine stimulation of the arachnoid through the platelet-derived growth factor receptor (PDGFR) using the RCAStv-a system. To specifically target arachnoid cells, the cells of origin of meningioma, we generated the PGDStv-a mouse (Prostaglandin D synthase). Forced expression of PDGF-B in arachnoid cells in vivo induced the formation of Grade I meningiomas in 27% of mice by 8 months of age. In vitro, PDGF-B overexpression in PGDS-positive arachnoid cells lead to increased proliferation.We found a correlation of PDGFR-B expression and NF2 inactivation in a cohort of human meningiomas, and we showed that, in mice, Nf2 loss and PDGF over-expression in arachnoid cells induced meningioma malignant transformation, with 40% of Grade II meningiomas. In these mice, additional loss of Cdkn2ab resulted in a higher incidence of malignant meningiomas with 60% of Grade II and 30% of Grade III meningiomas. These data suggest that chronic autocrine PDGF signaling can promote proliferation of arachnoid cells and is potentially sufficient to induce meningiomagenesis. Loss of Nf2 and Cdkn2ab have synergistic effects with PDGF-B overexpression promoting meningioma malignant transformation. PMID:26418719

  9. The transducible TAT-RIZ1-PR protein exerts histone methyltransferase activity and tumor-suppressive functions in human malignant meningiomas.

    PubMed

    Ding, Mao-Hua; Wang, Zhen; Jiang, Lei; Fu, Hua-Lin; Gao, Jie; Lin, Xian-Bin; Zhang, Chun-Lei; Liu, Zhen-Yang; Shi, Yi-Fei; Qiu, Guan-Zhong; Ma, Yue; Cui, Da-Xiang; Hu, Guo-Han; Jin, Wei-Lin

    2015-07-01

    Malignant meningiomas are a rare meningioma subtype and tend to have post-surgical recurrence. Significant endeavors have been taken to identify functional therapeutic targets to halt the growth of this aggressive cancer. We have recently discovered that RIZ1 is downregulated in high-grade meningiomas, and RIZ1 overexpression inhibits proliferation while promoting cell apoptosis of the IOMM-Lee malignant meningioma cell line. In this report, we show that the N-terminal PR domain of RIZ1 alone possessed growth-inhibitory activity and anticancer activity in primary human meningioma cells. Interestingly, the effects seem to be dependent on differential RIZ1 protein levels. Transducible TAT-RIZ1-PR protein could also inhibit meningioma tumor growth in nude mice models. We further demonstrate that PR protein exerts histone methyltransferase activity. A microarray analysis of TAT-RIZ1-PR-treated human malignant meningioma cells reveals 969 differentially expressed genes and 848 alternative splicing exons. Moreover, c-Myc and TXNIP, two putative downstream targets of H3K9 methylation, may be involved in regulating RIZ1 tumor-suppressive effects. The reciprocal relationship between RIZ1 and c-Myc was then validated in primary meningioma cells and human tumor samples. These findings provide insights into RIZ1 tumor suppression mechanisms and suggest that TAT-RIZ1-PR protein is a potential new epigenetic therapeutic agent for advanced meningiomas. PMID:25934289

  10. Cerebellar-Motor Dysfunction in Schizophrenia and Psychosis-Risk: The Importance of Regional Cerebellar Analysis Approaches

    PubMed Central

    Bernard, Jessica A.; Mittal, Vijay A.

    2014-01-01

    Motor abnormalities in individuals with schizophrenia and those at-risk for psychosis are well documented. An accumulating body of work has also highlighted motor abnormalities related to cerebellar dysfunction in schizophrenia including eye-blink conditioning, timing, postural control, and motor learning. We have also recently found evidence for motor dysfunction in individuals at ultra high-risk for psychosis (1–3). This is particularly relevant as the cerebellum is thought to be central to the cognitive dysmetria model of schizophrenia, and these overt motor signs may point to more general cerebellar dysfunction in the etiology of psychotic disorders. While studies have provided evidence indicative of motor cerebellar dysfunction in at-risk populations and in schizophrenia, findings with respect to the cerebellum have been mixed. One factor potentially contributing to these mixed results is the whole-structure approach taken when investigating the cerebellum. In non-human primates, there are distinct closed-loop circuits between the cerebellum, thalamus, and brain with motor and non-motor cortical regions. Recent human neuroimaging has supported this finding and indicates that there is a cerebellar functional topography (4), and this information is being missed with whole-structure approaches. Here, we review cerebellar-motor dysfunction in individuals with schizophrenia and those at-risk for psychosis. We also discuss cerebellar abnormalities in psychosis, and the cerebellar functional topography. Because of the segregated functional regions of the cerebellum, we propose that it is important to look at the structure regionally in order to better understand its role in motor dysfunction in these populations. This is analogous to approaches taken with the basal ganglia, where each region is considered separately. Such an approach is necessary to better understand cerebellar pathophysiology on a macro-structural level with respect to the pathogenesis of

  11. Taxonomic Synopsis of the Ponto-Mediterranean Ants of Temnothorax nylanderi Species-Group

    PubMed Central

    Csősz, Sándor; Heinze, Jürgen; Mikó, István

    2015-01-01

    In the current revisionary work, the Temnothorax nylanderi species-group of myrmicine ants is characterized. Eighteen species belonging to this group in the Ponto-Mediterranean region are described or redefined based on an integrative approach that combines exploratory analyses of morphometric data and of a 658bp fragment of the mitochondrial gene for the cytochrome c oxidase subunit I (CO I). The species group is subdivided into five species complexes: T. angustifrons complex, T. lichtensteini complex, T. nylanderi complex, T. parvulus complex, T. sordidulus complex, and two species, T. angulinodis sp. n. and T. flavicornis (Emery, 1870) form their own lineages. We describe seven new species (T. angulinodis sp. n., T. angustifrons sp. n., T. ariadnae sp. n., T. helenae sp. n., T. lucidus sp. n., T. similis sp. n., T. subtilis sp. n.), raise T. tergestinus (FINZI, 1928) stat.n. to species level, and propose a new junior synonymy for T. saxonicus (SEIFERT, 1995) syn.n. (junior synonym of T. tergestinus). We describe the worker caste and provide high quality images and distributional maps for all eighteen species. Furthermore, we provide a decision tree as an alternative identification key that visually gives an overview of this species-group. We make the first application to Formicidae of the Semantic Phenotype approach that has been used in previous taxonomic revisions. PMID:26536033

  12. Molecular analysis of phylogeographic subspecies in three Ponto-Caspian sturgeon species

    PubMed Central

    Dudu, Andreea; Georgescu, Sergiu Emil; Costache, Marieta

    2014-01-01

    Sturgeons (Order Acipenseriformes) represent an extremely valuable natural resource that is now facing depletion. In the current study we evaluate if the traditional classification in subspecies of Acipenser gueldenstaedtii, Acipenser stellatus and Huso huso, endemic to Ponto-Caspian region is sustained by molecular analysis and if these represent Evolutionary Significant Units (ESUs) that should be managed separately in conservation programs. To examine the classification of taxonomic entities we sequenced a fragment of the mitochondrial control region in case of three sturgeon species that inhabit the North-western of Black Sea and migrate for reproduction in the Lower Danube. Beside these sequences, we used previously published sequences from sturgeon individuals sampled in the Black Sea, Azov Sea and Caspian Sea. We determined the genetic diversity and genetic differentiation, conducted a Population Aggregation Analysis (PAA) and inferred an intraspecific molecular phylogeny and haplotype network. The results indicated a low level of genetic differentiation between the geographically designated subspecies and did not support a significant divergence or reciprocal monophyly between them. Our results confirm previous genetic studies with smaller samples sizes, but additional analyses including nuclear markers should be conducted for proper recommendations aiming at the development of conservation programs. PMID:25249783

  13. Tonic inhibition and ponto-geniculo-occipital-related activities shape abducens motoneuron discharge during REM sleep

    PubMed Central

    Escudero, Miguel; Márquez-Ruiz, Javier

    2008-01-01

    Eye movements, ponto-geniculo-occipital (PGO) waves, muscular atonia and desynchronized cortical activity are the main characteristics of rapid eye movement (REM) sleep. Although eye movements designate this phase, little is known about the activity of the oculomotor system during REM sleep. In this work, we recorded binocular eye movements by the scleral search-coil technique and the activity of identified abducens (ABD) motoneurons along the sleep–wake cycle in behaving cats. The activity of ABD motoneurons during REM sleep was characterized by a tonic decrease of their mean firing rate throughout this period, and short bursts and pauses coinciding with the occurrence of PGO waves. We demonstrate that the decrease in the mean firing discharge was due to an active inhibition of ABD motoneurons, and that the occurrence of primary and secondary PGO waves induced a pattern of simultaneous but opposed phasic activation and inhibition on each ABD nucleus. With regard to eye movements, during REM sleep ABD motoneurons failed to codify eye position as during alertness, but continued to codify eye velocity. The pattern of tonic inhibition and the phasic activations and inhibitions shown by ABD motoneurons coincide with those reported in other non-oculomotor motoneurons, indicating that the oculomotor system – contrary to what has been accepted until now – is not different from other motor systems during REM sleep, and that all motor systems are receiving similar command signals during this period. PMID:18499728

  14. Role of cerebellar adrenomedullin in blood pressure regulation.

    PubMed

    Figueira, Leticia; Israel, Anita

    2015-12-01

    Adrenomedullin (AM) and their receptor components, calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP1, RMP2 and RAMP3) are widely expressed in the central nervous system, including cerebellum. We have shown that AM binding sites are altered in cerebellum during hypertension, suggesting a role for cerebellar adrenomedullinergic system in blood pressure regulation. To further evaluate the role of AM in cerebellum, we assessed the expression of AM, RAMP1, RAMP2, RAMP3 and CRLR in the cerebellar vermis of 8 and 16week old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. In addition, the effect of microinjection of AM into rat cerebellar vermis on arterial blood pressure (BP) was determined. Animals were sacrificed by decapitation and cerebellar vermis was dissected for quantification of AM, CRLR, RAMP1, RAMP2 and RAMP3 expression using western blot analysis. Another group of male, 16week old SHR and WKY rats was anesthetized, and a cannula was implanted in the cerebellar vermis. Following recovery AM (0.02 to 200pmol/5μL) or vehicle was injected into cerebellar vermis. BP was determined, before and after treatments, by non-invasive plethysmography. In addition, to establish the receptor subtype involved in AM action in vivo, animals received microinjections of AM22-52 (200pmol/5μL), an AM1 receptor antagonist, or the CGRP1 receptor antagonist, CGRP8-37 (200pmol/5μL) into the cerebellar vermis, administered simultaneously with AM or vehicle microinjection. Cannulation was verified post mortem with the in situ injection of a dye solution. Our findings demonstrated that the expression of CRLR, RAMP1 and RAMP3 was higher in cerebellum of SHR rats, while AM and RAMP2 expression was lower than those of WKY rats, both in 8 and 16week old rats. In vivo microinjection of AM into the cerebellar vermis caused a profound, dose dependent, hypotensive effect in SHR but not in normotensive WKY rats. Coinjections of a

  15. Cerebellar control of postural scaling and central set in stance.

    PubMed

    Horak, F B; Diener, H C

    1994-08-01

    1. The effects of cerebellar deficits in humans on scaling the magnitude of automatic postural responses based on sensory feedback and on predictive central set was investigated. Electromyographic (EMG) and surface reactive torques were compared in patients with anterior lobe cerebellar disorders and in normal healthy adults exposed to blocks of four velocities and five amplitudes of surface translations during stance. Correlations between the earliest postural responses (integrated EMG and initial rate of change of torque) and translation velocity provided a measure of postural magnitude scaling using sensory information from the current displacement. Correlations of responses with translation amplitude provided a measure of scaling dependent on predictive central set based on sequential experience with previous like displacements because the earliest postural responses occurred before completion of the displacements and because scaling to displacement amplitude disappeared when amplitudes were randomized in normal subjects. 2. Responses of cerebellar patients to forward body sway induced by backward surface displacements were hypermetric, that is, surface-reactive torque responses were two to three times larger than normal with longer muscle bursts resulting in overshooting of initial posture. Despite this postural hypermetria, the absolute and relative latencies of agonist muscle bursts at the ankle, knee, and hip were normal in cerebellar patients. 3. Although they were hypermetric, the earliest postural responses of cerebellar patients were scaled normally to platform displacement velocities using somatosensory feedback. Cerebellar patients, however, were unable to scale initial postural response magnitude to expected displacement amplitudes based on prior experience using central set. Randomization of displacement amplitudes eliminated the set effect of amplitude on initial responses in normal subjects, but responses to randomized and blocked trials were not

  16. Abnormal cerebellar volume in acute and remitted major depression.

    PubMed

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Hirjak, Dusan; Thomann, Philipp A; Wolf, Robert C

    2016-11-01

    Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well. PMID:27321187

  17. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test.

    PubMed

    Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F M J

    2014-01-01

    Emulating the input-output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model's inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans. PMID:25152887

  18. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

    PubMed Central

    Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H.; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F. M. J.

    2014-01-01

    Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model’s inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans. PMID:25152887

  19. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

    PubMed

    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications. PMID:25578036

  20. Cerebellar hypoplasia of genetic origin in calves.

    PubMed

    O'Sullivan, B M; McPhee, C P

    1975-10-01

    Within 2 years, following the introduction of 2 Shorthorn bulls from the same stud into an Australian Illawarra Shorthorn (AIS) herd, 16 calves were born with cerebellar hypoplasia. All affected calves were the progeny of one bull mated to the daughters of the other. All other progeny of these bulls, most of which were from AIS dams, were normal. Affected calves exhibited severe ataxia, consistent head movement and abduction of the forelimbs. Microscopic changes in the cerebellum included sparsity of cells of the granular layer, loss of Purkinje cells and narrowing of the molecular layer. Observations on the frequencies of normal and abnormal calves are consistent with the hypothesis that the condition is caused by an autosomal recessive gene for which affected calves were homozygous and which was introduced into the herd in heterozygous condition by both of the Shorthorn bulls. Evidence is given for an unusually high frequency of the gene in the stud of origin of the Shorthorn bulls and a procedure for reducing its frequency is outlined. The possibility of a viral or toxic aetiology is discussed but is considered to be an unlikely explanation for the condition in this herd. PMID:1200928

  1. Multiplexed coding by cerebellar Purkinje neurons

    PubMed Central

    Hong, Sungho; Negrello, Mario; Junker, Marc; Smilgin, Aleksandra; Thier, Peter; De Schutter, Erik

    2016-01-01

    Purkinje cells (PC), the sole output neurons of the cerebellar cortex, encode sensorimotor information, but how they do it remains a matter of debate. Here we show that PCs use a multiplexed spike code. Synchrony/spike time and firing rate encode different information in behaving monkeys during saccadic eye motion tasks. Using the local field potential (LFP) as a probe of local network activity, we found that infrequent pause spikes, which initiated or terminated intermittent pauses in simple spike trains, provide a temporally reliable signal for eye motion onset, with strong phase-coupling to the β/γ band LFP. Concurrently, regularly firing, non-pause spikes were weakly correlated with the LFP, but were crucial to linear encoding of eye movement kinematics by firing rate. Therefore, PC spike trains can simultaneously convey information necessary to achieve precision in both timing and continuous control of motion. DOI: http://dx.doi.org/10.7554/eLife.13810.001 PMID:27458803

  2. Morphological characteristics of the superior cerebellar artery.

    PubMed

    Dodevski, A; Tosovska Lazarova, D; Zhivadinovik, J; Lazareska, M; Stojovska-Jovanovska, E

    2015-01-01

    With the introduction of new techniques in diagnostic and interventional radiology and progress in micro neurosurgery, accurate knowledge of the brain blood vessels is essential for daily clinical work. The aim of this study was to describe the morphological characteristics of the superior cerebellar artery and to emphasize their clinical significance. In this study we examined radiographs of 109 patients who had CT angiography at the University Clinic for Radiology in Skopje, R. Macedonia. This study included 49 females and 60 males, ranging in age from 27 to 83 years; mean age 57.4 ± 11.8 years. In 105 patients SCA arose from the basilar artery on both sides as a single vessel. In two patients SCA arose as a duplicate trunk from the basilar artery. We found unilateral duplication on the right SCA in one patient, and bilateral duplication in one patient. In two patients was noticed origin of the SCA from PCA as a single trunk from adult type of the PCA. Through knowledge of the anatomy and variations of SCA is important for clinicians as well as basic scientists who deal with problems related to intracranial vasculature in daily basis for save performance of diagnostic and interventional procedures. PMID:26076777

  3. Case of Langerhans Cell Histiocytosis That Mimics Meningioma in CT and MRI

    PubMed Central

    Zhu, Ming; Yu, Bing-Bing; Zhai, Ji-Liang

    2016-01-01

    Langerhans cell histiocytosis (LCH) is a rare disorder histologically characterized by the proliferation of Langerhans cells. Here we present the case of a 13-year-old girl with LCH wherein CT and MRI results led us to an initially incorrect diagnosis of meningioma. The diagnosis was corrected to LCH based on pathology findings. An intracranial mass was found mainly in the dura mater, with thickening of the surrounding dura. It appeared to be growing downward from the calvaria, pressing on underlying brain tissue, and had infiltrated the inner skull, causing a bone defect. The lesion was calcified with the typical dural tail sign. The dural origin of the lesion was verified upon surgical dissection. There are no previous reports in the literature describing LCH of dural origin presenting in young patients with typical dural tail signs and meningioma-like imaging findings. The current case report underscores the need for thorough histological and immunocytochemical examinations in LCH differential diagnosis. PMID:26962425

  4. Case of Langerhans Cell Histiocytosis That Mimics Meningioma in CT and MRI.

    PubMed

    Zhu, Ming; Yu, Bing-Bing; Zhai, Ji-Liang; Sun, Gang

    2016-03-01

    Langerhans cell histiocytosis (LCH) is a rare disorder histologically characterized by the proliferation of Langerhans cells. Here we present the case of a 13-year-old girl with LCH wherein CT and MRI results led us to an initially incorrect diagnosis of meningioma. The diagnosis was corrected to LCH based on pathology findings. An intracranial mass was found mainly in the dura mater, with thickening of the surrounding dura. It appeared to be growing downward from the calvaria, pressing on underlying brain tissue, and had infiltrated the inner skull, causing a bone defect. The lesion was calcified with the typical dural tail sign. The dural origin of the lesion was verified upon surgical dissection. There are no previous reports in the literature describing LCH of dural origin presenting in young patients with typical dural tail signs and meningioma-like imaging findings. The current case report underscores the need for thorough histological and immunocytochemical examinations in LCH differential diagnosis. PMID:26962425

  5. 68Ga DOTATATE PET/CT of Synchronous Meningioma and Prolactinoma.

    PubMed

    Basu, Sandip; Ranade, Rohit; Hazarika, Suman

    2016-03-01

    Ga DOTATATE PET/CT in noninvasive characterization of synchronous pituitary neoplasm and meningioma in a 38-year-old man is illustrated. The patient presented with an MRI-detected lobulated enhancing sellar-suprasellar mass with erosion of bony sella measuring 4.5 × 3.5 × 3.4 cm (with differential diagnosis with germ cell tumor) and a right parafalcine mass (2.7 × 2.6 cm) suggesting meningioma. Ga DOTATATE PET/CT demonstrated intense uptake in both lesions, suggesting the sellar mass to be pituitary macroadenoma. The finding of high serum prolactin and normal LH, FSH, cortisol, and testosterone levels suggested diagnosis of prolactinoma, and the patient was started on cabergoline. PMID:26462040

  6. Primary dural non-hodgkin's lymphoma mimicking meningioma: A case report and review of literature.

    PubMed

    Kudrimoti, Jyoti K; Gaikwad, Manish J; Puranik, Shaila C; Chugh, Ashish P

    2015-01-01

    A 42-year-old immunocompetent female presented with headache, vomiting and diminished unilateral vision. Computed tomography and magnetic resonance imaging were suggestive of high-grade meningioma. Neurological examination and routine hematological parameters were within normal limits. Craniotomy was performed; the tumor was arising from the dura mater, which was completely resected. Hematoxylin and eosin showed lesion comprising a tumor mass with monomorphic population of tumor cells arranged in sheets and small follicles. The tumor cells were immunoreactive for leukocyte common antigen and CD20 and immunonegative for glial fibrillary acid protein, epithelial membrane antigen, cytokeratin, CD3 and CD30. Rest of the body scan was normal. A diagnosis of primary dural non-Hodgkin's lymphoma was made. We report this exceedingly rare case of primary dural non-Hodgkin's lymphoma, which mimicked clinically and radiologically as meningioma. PMID:26458614

  7. Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy.

    PubMed

    Vadivelu, Sudhakar; Sharer, Leroy; Schulder, Michael

    2010-05-01

    The authors present the case of a patient that demonstrates the long-standing use of megestrol acetate, a progesterone agonist, and its association with multiple intracranial meningioma presentation. Discontinuation of megestrol acetate led to shrinkage of multiple tumors and to the complete resolution of one tumor. Histological examination demonstrated that the largest tumor had high (by > 25% of tumor cell nuclei) progesterone-positive expression, including progesterone receptor (PR) isoform B, compared with low expression of PR isoform A; there was no evidence of estrogen receptor expression and only unaccentuated collagen expression. This is the first clinical report illustrating a causal relationship between exogenous hormones and modulation of meningioma biology in situ. PMID:19731987

  8. Case-control study of intracranial meningiomas in women in Los Angeles County, California

    SciTech Connect

    Preston-Martin, S.; Paganini-Hill, A.; Henderson, B.E.; Pike, M.C.; Wood, C.

    1980-07-01

    A case-control study was conducted among women in Los Angeles County to investigate possible causes of intracranial meningiomas. Questionnaires sought information from patients and from a neighbor of each one on characteristics and past experiences that might be associated with the development of this disease. Information was obtained on 188 matched patient-neighbor pairs. Three primary factors appeared to be associated with meningioma occurrence: 1) a history of head trauma (odds ratio = 2.0, p = 0.01), 2) consumption of certain cured meats (odds ratio = 2.8, p = less than 0.01), and 3) exposure to medical and dental diagnostic X-rays to the head. For diagnostic X-rays, the strongest association was with early exposure (less than 20 yr old) to full-mouth dental X-ray series (odds ratio = 4.0, p less than 0.01).

  9. LED illumination effects on proliferation and survival of meningioma cellular cultures

    NASA Astrophysics Data System (ADS)

    Solarte, Efrain; Urrea, Hernan; Criollo, William; Gutierrez, Oscar

    2010-02-01

    Meningioma cell cultures were prepared from frozen cell samples in 96 wells culture plates. Semiconductor light sources (LED) in seven different wavelength ranges were used to illuminate the wells, three different irradiation doses were selected per LED. Control cultures using three different concentrations of FBS were processed for comparison. Cell proliferation, viability, and cytotoxicity were measured every 24 hours for 6 days, using the XTT colorimetric assay (RocheR). None of the irradiated cultures exhibit cytotoxicity; but some of them exhibit proliferation inhibition. The larger proliferation was detected at a 0.05J/cm2 dose, for all LEDs; but for the orange and violet LEDs generated the bigger proliferation rate was measured. Results show the improvement of meningioma cell proliferation using illumination in some given wavelength ranges.

  10. A dumbbell-shaped meningioma mimicking a schwannoma in the thoracic spine.

    PubMed

    Kim, Myeong-Soo; Eun, Jong-Pil; Park, Jeong-Soo

    2011-09-01

    A 50-year-old man presented bilateral hypesthesia on and below the T6 dermatome and paresthesia. Magnetic resonance imaging (MRI) showed an intraspinal extradural tumor, which located from the 6th thoracic vertebral body to the upper margin of the 7th vertebral body, continuing dumbbell-like through the intervertebral foramen into the right middle thorax suggesting a neurogenic tumor (neurofibroma or neurilemmoma). With the patient in a prone position, we exposed and excised the tumor via a one stage posterior approach through a hemi-laminictomy of T6. Histologic examination showed a grade 1 meningothelial meningioma, according to the World Health Organization classification. Initially, we assumed the mass was a schwannoma because of its location and dumbbell shape. However, the tumor was actually a meningioma. Postoperatively, hypesthesia resolved completely and motor power of the leg gradually full recovered. A postoperative MRI revealed no evidence of residual tumor. PMID:22102962

  11. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model

    PubMed Central

    Luque, Niceto R.; Garrido, Jesús A.; Naveros, Francisco; Carrillo, Richard R.; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range). PMID:26973504

  12. Natural Compounds as Potential Treatments of NF2-Deficient Schwannoma and Meningioma: Cucurbitacin D and Goyazensolide

    PubMed Central

    Spear, Samuel A.; Burns, Sarah S.; Oblinger, Janet L.; Ren, Yulin; Pan, Li; Kinghorn, A. Douglas; Welling, D. Bradley; Chang, Long-Sheng

    2015-01-01

    Hypothesis Cucurbitacin D and goyazensolide, two plant-derived natural compounds, possess potent growth-inhibitory activity in schwannoma and meningioma cells. Background Currently, no FDA-approved drugs are available for neurofibromatosis type 2 (NF2)-associated schwannomas and meningiomas. Selected natural compounds with antineoplastic activity, such as cucurbitacin and goyazensolide, may be developed as potential treatments for these tumors. Methods The Nf2-deficient mouse schwannoma Sch10545 and human benign meningioma Ben-Men-1 cells were treated with various concentrations of cucurbitacin D and goyazensolide. The effect on cell proliferation was determined using resazurin assays. Flow cytometry was used to assess the cell cycle profiles. Western blot analysis was performed to investigate the expression of various signal molecules related to the cell cycle and the AKT pathway. Results Cucurbitacin D inhibited proliferation of Sch10545 cells (IC50 ~0.75 μM) and Ben-Men-1 cells (IC50 ~0.2 μM). Goyazensolide also reduced cell proliferation of Sch10545 cells (IC50 ~0.9 μM) and Ben-Men-1 cells (IC50 ~1 μM). The G2/M population increased in both Sch10545 and Ben-Men-1 cells treated with cucurbitacin D or goyazensolide around the IC50. Cucurbitacin and goyazensolide substantially reduced the levels of cyclins E and A in treated Sch10545 and Ben-Men-1 cells. Cucurbitacin D also inhibited cyclin B, phospho-AKT and phospho-PRAS40 expression. In addition, goyazensolide reduced the levels of phospho-AKT and NFκB and increased the expression of pro-apoptotic Bim in Sch10545 and Ben-Men-1 cells. Conclusions Both cucurbitacin D and goyazensolide effectively inhibit proliferation of NF2-deficient schwannoma and meningioma cells, suggesting that these natural compounds should be further evaluated as potential treatments for NF2-related tumors. PMID:23928514

  13. Intensity-modulated stereotactic radiotherapy (IMSRT) for skull-base meningiomas

    SciTech Connect

    Yenice, Kamil M. . E-mail: kyenice@radonc.uchicago.edu; Narayana, Ashwatha; Chang, Jenghwa; Gutin, Philip H.; Amols, Howard I.

    2006-11-15

    Purpose: To investigate the potential benefits of a micromultileaf collimator ({mu}MLC) -based intensity-modulated stereotactic radiotherapy (IMSRT) in skull-base meningiomas. Methods and Materials: Seven patients with inoperable or recurrent small-volume (1.7-15.5 cc) skull-base meningiomas were treated with IMSRT to 54 Gy in 30 fractions using a {mu}MLC in the dynamic mode. IMSRT plan quality was evaluated in comparison with the conformal stereotactic radiotherapy technique, using the same beam arrangement and static delivery with the {mu}MLC. Plans were compared using multiple dose distributions and dose-volume histograms for the planning target volume and organs at risk. The conformity and uniformity metrics, as well as normal-tissue complication probabilities, were calculated for the two techniques. Follow-up with MRI and clinical examination was performed at regular intervals. Results: With a mean follow-up of 17 months, local control has been achieved in all cases, and no treatment-related toxicities have been noted. For cavernous sinus tumors overlapping with optic apparatus, IMSRT has improved the dose uniformity within the target on average by 8%, which resulted in a reduction of the estimated chiasm normal-tissue complication probability by up to 65%. Conclusions: Intensity-modulated stereotactic radiotherapy can be safely delivered to improve the dose distributions in select skull-base meningiomas with an appreciable concomitant dose reduction to involved critical structures. Longer follow-up with a larger patient group is necessary to demonstrate sustained tumor control and low morbidity with IMSRT for small inoperable, recurrent, or subtotally resected meningiomas.

  14. Nrf2 Expressions Correlate with WHO Grades in Gliomas and Meningiomas

    PubMed Central

    Tsai, Wen-Chiuan; Hueng, Dueng-Yuan; Lin, Chii-Ruey; Yang, Thomas C. K.; Gao, Hong-Wei

    2016-01-01

    Background: Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as Nrf2) is associated with cellular progression and chemotherapeutic resistance in some human cancers. We tested the relationship between Nrf2 expression and survival of patients with primary brain tumors (PBTs). Methods: In order to realize Nrf2 protein expression in gliomas, Western blot analysis was performed in normal brain tissue and U87MG, LN229, GBM8401 and U118MG glioma cell lines protein lysates. Then, U87MG, LN229, and GBM8401 mRNA were applied to performed quantitative RT-PCR for detect Nrf2 gene expression in glioma cell lines. At last, immunohistochemical analysis was used to determine the expression of Nrf2 in samples from 178 PBTs and 10 non-neoplastic brain tissues. Results: In these included in vitro studies, both Nrf2 protein and mRNA expression in all human glioma cell lines were higher than normal brain tissue. Similarly, on the viewpoint of immunohistochemistry, Nrf2 expression in gliomas were positively correlated with World Health Organization (WHO) grades. Additionally, compared with the expression of Nrf2 in non-neoplastic brain tissue, expression in meningiomas was of a stronger intensity and was present in a higher percentage of cells. Furthermore, scores were significantly higher in WHO grade II than in WHO grade I meningiomas. Finally, overall survival tended to be shorter in patients whose PBTs had higher expression of Nrf2, although the correlation was not statistically significant. Conclusions: Nrf2 overexpression positively correlated with WHO grade in gliomas and meningiomas. On the other hand, Nrf2 immunohistochemical stain could help pathologists to differentiate atypical meningiomas from benign tumors. Therefore, Nrf2 expression may be a useful biomarker to predict WHO grade and cellular behavior of PBTs. PMID:27187376

  15. Cognitive dysfunction might be improved in association with recovered neuronal viability after intracranial meningioma resection.

    PubMed

    Koizumi, Hiroyasu; Ideguchi, Makoto; Iwanaga, Hideyuki; Shirao, Satoshi; Sadahiro, Hirokazu; Oka, Fumiaki; Suehiro, Eiichi; Yoneda, Hiroshi; Ishihara, Hideyuki; Nomura, Sadahiro; Suzuki, Michiyasu

    2014-07-29

    Intracranial meningiomas are the most common types of neoplasms that cause mental disorders. Although higher brain function can be restored and even improved in some patients after tumor resection, the mechanisms remain unclear. We investigated changes in the brains of patients after resection of an intracranial meningioma using (123)I-Iomazenil (IMZ)-single photon emission computed tomography (SPECT). Ten patients underwent IMZ-SPECT within 4 weeks before and 3 months after intracranial meningioma resection. Changes in IMZ accumulation in brain parenchyma were assessed as ratios of counts in the lesion-to-contralateral hemisphere (L/C ratios). Mean Mini-Mental State Examination scores before and after resection of 19.9±11.4 vs. 26.5±3.8, respectively (p=0.03) indicated that the cognitive function of these patients was significantly improved after tumor resection. The average L/C ratios calculated from image counts of IMZ were 0.92±0.05 and 0.98±0.02 before and after surgery, respectively. The L/C ratio of IMZ accumulation was significantly decreased after tumor resection (p=0.0003). In contrast, regional cerebral blood flow calculated from (123)I-Iodoamphetamine-SPECT images did not significantly differ after tumor resection. The recovered binding potential of IMZ in brain parenchyma surrounding the tumor bulk after resection indicates that the viability of central benzodiazepine receptors was reversibly depressed and recoverable after release from compression by the tumor. The recovered neuronal viability revealed by IMZ-SPECT might be responsible for the improved cognitive function after intracranial meningioma resection. PMID:24928615

  16. Surgical limitations in convexity meningiomas en-plaque: Is radical resection necessary?

    PubMed

    Yao, Amy; Sarkiss, Christopher A; Lee, James; Zarzour, Hekmat K; Shrivastava, Raj K

    2016-05-01

    Meningiomas-en-plaque (MEP) comprise 2.5% of all meningiomas. While they typically arise in the sphenoid wing, convexity MEP are comparatively rare and are often confused with meningeal sarcoidosis, osteoma, tuberculoma, or fibrous dysplasia, with very little information published in the literature. We conducted a literature review on PubMed of English-only articles using a keyword search. All studies that described reports of convexity MEP were reviewed for patient demographics, presenting symptoms, radiological reports, surgical management, recurrence rates, histopathological presentation, post-operative complications, and follow-up. This resulted in 12 papers comprising 22 cases of convexity MEP. Seventeen (77%) of the 22 patients were female with an average age of 53.2years. Intitial presenting symptoms included headache in 12/20 (60%), hemiparesis in 5/20 (25%), and visual symptoms in 1/20 (5%). Of the 14 patients who underwent surgical resection, only four were reported as gross total resection. Twelve reports had associated pathology reports, with all 12 tumors graded as World Health Organization Grade I. Convexity MEP, while rare, present a challenge with regard to correct diagnosis and subsequent resection. The easier accessibility of these meningiomas predicts higher surgical success rates and incidence of total resection, though care must be taken to ensure gross total removal of tumor, dural attachments, and any overlying hyperostotic bone. Though hyperostosis is frequently observed with this variant of meningioma, it is neither exclusive nor wholly indicative of MEP. Due to its rarity in both clinical practice and the literature, further studies are warranted to identify modern imaging means to correctly diagnose this condition. PMID:26778515

  17. Anesthetic Management of a Patient with Myasthenia Gravis for Meningioma Surgery - A Case Report.

    PubMed

    Srivastava, V K; Agrawal, S; Ahmed, M; Sharma, S

    2015-01-01

    Myasthenia gravis is a disease of great challenge to the anesthesiologist, because it affects the neuromuscular junction. Anesthetic management involves either muscle relaxant or non-muscle relaxant techniques. This case report documents the safe use of fentanyl, propofol and sevoflurane combination guided by bispectral index, without the use of muscle relaxants in a patient with myasthenia gravis who presented for meningioma surgery. PMID:26620756

  18. Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas.

    PubMed

    Lomas, Jesus; Bello, M Josefa; Arjona, Dolores; Alonso, M Eva; Martinez-Glez, Victor; Lopez-Marin, Isabel; Amiñoso, Cinthia; de Campos, Jose M; Isla, Alberto; Vaquero, Jesus; Rey, Juan A

    2005-03-01

    The role of the NF2 gene in the development of meningiomas has recently been documented; inactivating mutations plus allelic loss at 22q, the site of this gene (at 22q12), have been identified in both sporadic and neurofibromatosis type 2-associated tumors. Although epigenetic inactivation through aberrant CpG island methylation of the NF2 5' flanking region has been documented in schwannoma (another NF2-associated neoplasm), data on participation of this epigenetic modification in meningiomas are not yet widely available. Using methylation-specific PCR (MSP) plus sequencing, we assessed the presence of aberrant promoter NF2 methylation in a series of 88 meningiomas (61 grade I, 24 grade II, and 3 grade III), in which the allelic constitution at 22q and the NF2 mutational status also were determined by RFLP/microsatellite and PCR-SSCP analyses. Chromosome 22 allelic loss, NF2 gene mutation, and aberrant NF2 promoter methylation were detected in 49%, 24%, and 26% of cases, respectively. Aberrant NF2 methylation with loss of heterozygosity (LOH) at 22q was found in five cases, and aberrant methylation with NF2 mutation in another; LOH 22q and the mutation were found in 16 samples. The aberrant methylation of the NF2 gene also was the sole alteration in 15 samples, most of which were from grade I tumors. These results indicate that aberrant NF2 hypermethylation may participate in the development of a significant proportion of sporadic meningiomas, primarily those of grade I. PMID:15609345

  19. A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma.

    PubMed

    Zhi, Feng; Shao, Naiyuan; Li, Bowen; Xue, Lian; Deng, Danni; Xu, Yuan; Lan, Qing; Peng, Ya; Yang, Yilin

    2016-01-01

    Circulating microRNAs (miRNAs) hold great promise as novel clinically blood-based biomarkers for cancer diagnosis and prognosis. However, little is known about their impact in meningioma. The TLDA assay was performed as an initial survey to determine the serum miRNA expression profile in two pooled samples from 20 pre-operative meningiomas and 20 matched healthy controls. Selected candidate miRNAs were subsequently validated individually in another 210 patients and 210 healthy controls from two independent cohorts by qRT-PCR. The serum levels of miR-106a-5p, miR-219-5p, miR-375, and miR-409-3p were significantly increased, whereas the serum levels of miR-197 and miR-224 were markedly decreased. The area under the ROC curve (AUC) for the six combined miRNAs was 0.778. The 4 increased miRNAs were significantly decreased, while the 2 decreased miRNAs were significantly increased after tumor removal. Furthermore, the expression levels of miR-224 were associated with sex, and the expression levels of miR-219-5p were positively associated with the clinical stages of meningioma. Finally, the high expression of miR-409-3p and low expression of miR-224 were significantly correlated with higher recurrence rates. The present study revealed that the panel of 6 serum miRNA may have the potential to be used clinically as an auxiliary tool for meningioma patients. PMID:27558167

  20. A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma

    PubMed Central

    Zhi, Feng; Shao, Naiyuan; Li, Bowen; Xue, Lian; Deng, Danni; Xu, Yuan; Lan, Qing; Peng, Ya; Yang, Yilin

    2016-01-01

    Circulating microRNAs (miRNAs) hold great promise as novel clinically blood-based biomarkers for cancer diagnosis and prognosis. However, little is known about their impact in meningioma. The TLDA assay was performed as an initial survey to determine the serum miRNA expression profile in two pooled samples from 20 pre-operative meningiomas and 20 matched healthy controls. Selected candidate miRNAs were subsequently validated individually in another 210 patients and 210 healthy controls from two independent cohorts by qRT-PCR. The serum levels of miR-106a-5p, miR-219-5p, miR-375, and miR-409-3p were significantly increased, whereas the serum levels of miR-197 and miR-224 were markedly decreased. The area under the ROC curve (AUC) for the six combined miRNAs was 0.778. The 4 increased miRNAs were significantly decreased, while the 2 decreased miRNAs were significantly increased after tumor removal. Furthermore, the expression levels of miR-224 were associated with sex, and the expression levels of miR-219-5p were positively associated with the clinical stages of meningioma. Finally, the high expression of miR-409-3p and low expression of miR-224 were significantly correlated with higher recurrence rates. The present study revealed that the panel of 6 serum miRNA may have the potential to be used clinically as an auxiliary tool for meningioma patients. PMID:27558167

  1. Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study.

    PubMed

    Sheehan, Jason P; Cohen-Inbar, Or; Ruangkanchanasetr, Rawee; Bulent Omay, S; Hess, Judith; Chiang, Veronica; Iorio-Morin, Christian; Alonso-Basanta, Michelle; Mathieu, David; Grills, Inga S; Lee, John Y K; Lee, Cheng-Chia; Dade Lunsford, L

    2015-11-01

    Stereotactic radiosurgery (SRS) offers a high degree of tumor control for benign meningiomas. However, radiosurgery can occasionally incite edema or exacerbate pre-existing peri-tumoral edema. The current study investigates the incidence, timing, and extent of edema around parasagittal or parafalcine meningiomas following SRS. A retrospective multicenter review was undertaken through participating centers in the International Gamma Knife Research Foundation (previously the North American Gamma Knife Consortium or NAGKC). All included patients had a parafalcine or parasagittal meningioma and a minimum of 6 months follow up. The median follow up was 19.6 months (6-158 months). Extent of new or worsening edema was quantitatively analyzed using volumetric analysis; edema indices were longitudinally computed following radiosurgery. Analysis was performed to identify prognostic factors for new or worsening edema. A cohort of 212 patients comprised of 51.9 % (n = 110) females, 40.1 % upfront SRS and 59.9 % underwent adjuvant SRS for post-surgical residual tumor. The median tumor volume at SRS was 5.2 ml. Venous sinus compression or invasion was demonstrated in 25 % (n = 53). The median marginal dose was 14 Gy (8-20 Gy). Tumor volume control was determined in 77.4 % (n = 164 out of 212 patients). Tumor edema progressed and then regressed in 33 % (n = 70), was stable or regressed in 52.8 % (n = 112), and progressively worsened in 5.2 % (n = 11). Tumor location, tumor volume, venous sinus invasion, margin, and maximal dose were found to be significantly related to post-SRS edema in multivariate analysis. SRS affords a high degree of tumor control for patients with parasagittal or parafalcine meningiomas. Nevertheless, SRS can lead to worsening peritumoral edema in a subset of patients such as those with larger tumors (>10 cc) and venous sinus invasion/compression. Long-term follow up is required to detect and appropriately manage post-SRS edema. PMID:26329323

  2. Post-Treatment Edema after Meningioma Radiosurgery is a Predictable Complication

    PubMed Central

    Pontoriero, Antonio; Siddi, Francesca; Iatì, Giuseppe; Cardali, Salvatore; Angileri, Filippo F; Granata, Francesca; Pergolizzi, Stefano; Germanò, Antonino; Tomasello, Francesco

    2016-01-01

    Symptomatic post-treatment edema (PTE) causing seizures, focal deficits, and intracranial hypertension is a rather common complication of meningioma radiosurgery. Factors associated to the occurrence of PTE still needs to be clarified. We retrospectively analyzed our patients’ data to identify factors associated with the development of symptomatic PTE. Supposed risk factors were systematically analyzed. Between July 2007 and March 2014, 245 meningiomas in 229 patients were treated by a single fraction or multisession radiosurgery (2-5 fractions) or hypofractionated stereotactic radiotherapy (6-15 fractions) using the CyberKnife system (Accuray Inc., Sunnyvale, CA) at the University Hospital of Messina, Italy. Local tumor control was achieved in 200 of 212 patients with World Health Organization (WHO) Grade I meningiomas (94%) at a mean follow-up of 62 months. Symptomatic PTE on MRI was diagnosed in 19 patients (8.3%) causing seizure (n=17, 89%), aggravating headache (n=12, 63%), or focal deficits (n=13, 68%). Four variables were found to be associated with the likelihood of edema development, including tumor volume > 4.5 mL, non-basal tumor location, tight brain/tumor interface, and atypical histology. Nonetheless, when multivariate logistic regression analysis was performed, only tumor volume and brain-tumor interface turned out to be independent predictors of PTE development. Our results suggest that the factor associated with the risk of developing PTE is associated to characteristics of meningioma rather than to the treatment modality used. Accordingly, an appropriate patient selection is the way to achieve safe treatment and long-term disease control. PMID:27330873

  3. 18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas.

    PubMed

    Calabria, Ferdinando F; Chiaravalloti, Agostino; Calabria, Eros N; Grillea, Giovanni; Schillaci, Orazio

    2016-08-01

    A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas. PMID:27187729

  4. Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade

    PubMed Central

    Jungk, Christine; Sahm, Felix; Ull, Anna Theresa; Warta, Rolf; Lamszus, Katrin; Gousias, Konstantinos; Ketter, Ralf; Roesch, Saskia; Rapp, Carmen; Schefzyk, Sebastian; Urbschat, Steffi; Lahrmann, Bernd; Kessler, Almuth F.; Löhr, Mario; Senft, Christian; Grabe, Niels; Reuss, David; Beckhove, Philipp; Westphal, Manfred; von Deimling, Andreas; Unterberg, Andreas

    2016-01-01

    Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade. Unsupervised transcriptomic analysis in 62 meningiomas revealed transcriptional profiles lining up according to WHO grade and clinical subgroup. Notably aggressive subgroups (R+M tumors and WHO grade III) shared a large set of differentially expressed genes (n=332; p<0.01, FC>1.25). In an independent multicenter validation set (n=82), differential expression of 10 genes between WHO grades was confirmed. Additionally, among WHO grade I tumors differential expression between NR and aggressive R+M tumors was affirmed for PTTG1, AURKB, ECT2, UBE2C and PRC1, while MN1 and LEPR discriminated between NR and R+M WHO grade II tumors. Univariate survival analysis revealed a significant association with progression-free survival for PTTG1, LEPR, MN1, ECT2, PRC1, COX10, UBE2C expression, while multivariate analysis identified a prediction for PTTG1 and LEPR mRNA expression independent of gender, WHO grade and extent of resection. Finally, stainings of PTTG1 and LEPR confirmed malignancy-associated protein expression changes. In conclusion, based on the so far largest study sample of WHO grade III and recurrent meningiomas we report a comprehensive transcriptional landscape and two prognostic markers. PMID:26894859

  5. Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study

    PubMed Central

    Michaud, Dominique S.; Gallo, Valentina; Schlehofer, Brigitte; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Dahm, Christina C.; Kaaks, Rudolf; Lukanova, Annekatrin; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Bamia, Christina; Kyrozis, Andreas; Sacerdote, Carlotta; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Mattiello, Amalia; Bueno-de-Mesquita, H. Bas; Ros, Martine M.; Peeters, Petra H. M.; van Gils, Carla H.; Lund, Eiliv; Bakken, Kjersti; Gram, Inger T.; Barricarte, Aurelio; Navarro, Carmen; Dorronsoro, Miren; Sánchez, Maria José; Rodríguez, Laudina; Duell, Eric J; Hallmans, Göran; Melin, Beatrice S.; Manjer, Jonas; Borgquist, Signe; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E.; Tsilidis, Konstantinos K.; Romieu, Isabelle; Rinaldi, Sabina; Vineis, Paolo; Riboli, Elio

    2010-01-01

    Background The aetiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (CI). Results No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR = 1.62, 95% CI = 1.04-2.54) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR = 3.61, 95% CI = 1.75-7.46). Conclusion Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, appears to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. Impact Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. PMID:20802020

  6. [Usefulness of pulsed water jet in dissecting sphenoid ridge meningioma while preserving arteries].

    PubMed

    Endo, Toshiki; Nakagawa, Atsuhiro; Fujimura, Miki; Sonoda, Yukihiko; Shimizu, Hiroaki; Tominaga, Teiji

    2014-11-01

    We report the utility of a pulsed water jet device in meningioma surgery. The presented case is that of a 61-year-old woman with left visual disturbance. MRI demonstrated heterogeneously enhanced mass with intratumoral hemorrhage, indicating sphenoid ridge meningioma on her left side. The tumor invaded the cavernous sinus and left optic canal, engulfing the internal carotid artery in the carotid cistern and encased middle cerebral arteries. During the operation, the pulsed water jet device was useful for dissecting the tumor away from the arteries since it was safe in light of preserving parent arteries. The jet did not cause any vascular injury and did not induce vasospasm as shown by postoperative symptomatology and MRIs. With the aid of pulsed water jet, we could achieve total resection of the tumor except for the piece within the cavernous sinus. The patient had no new neurological deficits after the operation. We consider the pulsed water jet as a useful device, especially when the need to dissect meningioma from parent arteries exists. The jet can help neurosurgeons simultaneously achieve tumor resection and preservation of blood vessels. PMID:25351797

  7. Successful CyberKnife Irradiation of 1000 cc Hemicranial Meningioma: 6-year Follow-up

    PubMed Central

    Golanov, Andrey V.; Antipina, Natalia; Gorlachev, Gennady

    2015-01-01

    Meningiomas are common benign tumors with accepted treatment approaches and usually don't challenge healthcare specialists. We present a case of a huge unresectable hemicranial meningioma, which was successfully treated with hypofractionated irradiation. A male patient, sixty-two years of age, suffered for over 12 years from headaches, facial deformity, right eye displacement, right eye movement restriction, right-sided ptosis, and facial hypoesthesia. MRI and CT studies revealed an extended hemicranial meningioma. Prior to irradiation, the patient underwent four operations. Eventually, the tumor was irradiated with the CyberKnife in August 2009. Tumor volume composed 1085 cc. The mean dose of 35.3 Gy was delivered in 7 fractions (31.5 Gy at 72% isodose line comprising 95% of tumor volume). The patient was followed during six years and experienced only mild (Grade 1-2 CTCAE) acute skin and mucosa reactions. During the follow-up period, we observed target volume shrinkage for 17% (for 26% after excluding hyperostosis) and regression of intracranial hypertension signs. Due to the extreme volume and complex shape of the tumor, spreading along the surface of the hemisphere as well as an optic nerve involvement, the case presented would not be generally considered suitable for irradiation, especially for hypofractionation. We regard this clinical situation not as a treatment recommendation, but as a demonstration of the underestimated possibilities of hypofractionation regimen and CyberKnife system, both of which are limited with our habit of conventional treatments. PMID:26719827

  8. Diffusion-Weighted Imaging in Meningioma: Prediction of Tumor Grade and Association with Histopathological Parameters12

    PubMed Central

    Surov, Alexey; Gottschling, Sebastian; Mawrin, Christian; Prell, Julian; Spielmann, Rolf Peter; Wienke, Andreas; Fiedler, Eckhard

    2015-01-01

    OBJECTIVES: To analyze diffusion-weighted imaging (DWI) findings of meningiomas and to compare them with tumor grade, cell count, and proliferation index and to test a possibility of use of apparent diffusion coefficient (ADC) to differentiate benign from atypical/malignant tumors. METHODS: Forty-nine meningiomas were analyzed. DWI was done using a multislice single-shot echo-planar imaging sequence. A polygonal region of interest was drawn on ADC maps around the margin of the lesion. In all lesions, minimal ADC values (ADCmin) and mean ADC values (ADCmean) were estimated. Normalized ADC (NADC) was calculated in every case as a ratio ADCmean meningioma/ADCmean white matter. All meningiomas were surgically resected and analyzed histopathologically. The tumor proliferation index was estimated on Ki-67 antigen–stained specimens. Cell density was calculated. Collected data were evaluated by means of descriptive statistics. Analyses of ADC/NADC values were performed by means of two-sided t tests. RESULTS: The mean ADCmean value was higher in grade I meningiomas in comparison to grade II/III tumors (0.96 vs 0.80 × 10− 3 mm2s− 1, P = .006). Grade II/III meningiomas showed lower NADC values in comparison to grade I tumors (1.05 vs 1.26, P = .015). There was no significant difference in ADCmin values between grade I and II/III tumors (0.69 vs 0.63 × 10− 3 mm2s− 1, P = .539). The estimated cell count varied from 486 to 2091 (mean value, 1158.20 ± 333.74; median value, 1108). There were no significant differences in cell count between grade I and grade II/III tumors (1163.93 vs 1123.86 cells, P = .77). The mean level of the proliferation index was 4.78 ± 5.08%, the range was 1% to 18%, and the median value was 2%. The proliferation index was statistically significant higher in grade II/III meningiomas in comparison to grade I tumors (15.43% vs 3.00%, P = .001). Ki-67 was negatively associated with ADCmean (r = − 0.61, P < .001) and NADC (r = − 0.60, P

  9. Experience with 7.0 T MRI in Patients with Supratentorial Meningiomas.

    PubMed

    Song, Sang Woo; Son, Young Don; Cho, Zang-Hee; Paek, Sun Ha

    2016-07-01

    Meningiomas are typically diagnosed by their characteristic appearance on conventional magnetic resonance imaging (MRI). However, detailed image findings regarding peri- and intra-tumoral anatomical structures, tumor consistency and vascularity are very important in pre-surgical planning and surgical outcomes. At the 7.0 T MRI achieving ultra-high resolution, it could be possible to obtain more useful information in surgical strategy. Four patients who were radiologically diagnosed with intracranial meningioma in 1.5 T MRI underwent a 7.0 T MRI. Three of them underwent surgery afterwards, and one received gamma knife radiosurgery. In our study, the advantages of 7.0 T MRI over 1.5 T MRI were a more detailed depiction of the peri- and intra-tumoral vasculature and a clear delineation of tumor-brain interface. In the safety issues, all patients received 7.0 T MRI without any adverse event. One disadvantage of 7.0 T MRI was the reduced image quality of skull base lesions. 7.0 T MRI in patients with meningiomas could provide useful information in surgical strategy, such as the peri-tumoral vasculature and the tumor-brain interface. PMID:27446524

  10. Experience with 7.0 T MRI in Patients with Supratentorial Meningiomas

    PubMed Central

    Song, Sang Woo; Son, Young Don; Cho, Zang-Hee

    2016-01-01

    Meningiomas are typically diagnosed by their characteristic appearance on conventional magnetic resonance imaging (MRI). However, detailed image findings regarding peri- and intra-tumoral anatomical structures, tumor consistency and vascularity are very important in pre-surgical planning and surgical outcomes. At the 7.0 T MRI achieving ultra-high resolution, it could be possible to obtain more useful information in surgical strategy. Four patients who were radiologically diagnosed with intracranial meningioma in 1.5 T MRI underwent a 7.0 T MRI. Three of them underwent surgery afterwards, and one received gamma knife radiosurgery. In our study, the advantages of 7.0 T MRI over 1.5 T MRI were a more detailed depiction of the peri- and intra-tumoral vasculature and a clear delineation of tumor-brain interface. In the safety issues, all patients received 7.0 T MRI without any adverse event. One disadvantage of 7.0 T MRI was the reduced image quality of skull base lesions. 7.0 T MRI in patients with meningiomas could provide useful information in surgical strategy, such as the peri-tumoral vasculature and the tumor-brain interface. PMID:27446524

  11. Anterior Microsurgical Approach to Ventral Lower Cervical Spine Meningiomas: Indications, Surgical Technique and Long Term Outcome.

    PubMed

    Fraioli, Mario F; Marciani, Maria G; Umana, Giuseppe E; Fraioli, Bernardo

    2015-08-01

    Ventral lower cervical spinal meningiomas with posterior displacement of the spinal cord are rare and anterior approach has been rarely reported in the literature. The authors present their experience about eight patients operated through anterior microsurgical approach. Exposure of meningiomas was achieved through one or two corpectomies, according to meningioma extension. Tumour removal was performed thanks to the aid of a dedicated ultrasonic aspirator, and intraoperative evoked potentials were employed. Particular care was taken with the materials adopted for reconstruction of the anterior dural plane, to avoid postoperative cerebrospinal fluid leak. Vertebral fusion and stabilization were achieved by tantalum cage or titanium graft in case of one or two corpectomies respectively; anterior titanium plate fixed with screws was applied in all patients. Extent of tumour removal was related to the presence of a conserved arachnoidal plane between the tumour and the spinal cord: total removal was achieved in 2 patients, while gross total removal in the other six ones. Postoperative neurological outcome, which was favourable in all patients, was related mostly to preoperative neurologic status. No recurrence after total removal and no remnant growth after gross total removal occurred during an average follow-up period of 6, 7 years. PMID:26269613

  12. Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma

    SciTech Connect

    Dumanski, J.P.; Carlbom, E.; Collins, V.P.; Nordenskjoeld, M.

    1987-12-01

    The genotypes were analyzed at 11 polymorphic DNA loci (restriction fragment length alleles) on chromosome 22 in tumor and normal tissues from 35 unrelated patients with meningiomas. Sixteen tumors retained the constitutional genotype along chromosome 22, while 14 tumors (40%) showed loss of one constitutional allele at all informative loci, consistent with monosomy 22 in the tumor DNA. The remaining 5 tumors (14%) showed loss of heterozygosity in the tumor DNA at one or more chromosome 22 loci and retained heterozygosity at other loci, consistent with variable terminal deletions of one chromosome 22 in the tumor DNA. The results suggest that a meningioma locus is located distal to the myoglobin locus, within 22q12.3-qter. Multiple loci on their chromosomes also were studied, and 12 of the 19 tumors with losses of chromosome 22 alleles showed additional losses of heterozygosity at loci on one to three other chromosomes. All tumors that retained the constitutional genotype on chromosome 22 also retained heterozygosity at all informative loci on other chromosomes analyzed, suggesting that the rearrangement of chromosome 22 is a primary event in the tumorigenesis of meningioma.

  13. Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection.

    PubMed

    Potapov, A A; Goryaynov, S A; Okhlopkov, V A; Shishkina, L V; Loschenov, V B; Savelieva, T A; Golbin, D A; Chumakova, A P; Goldberg, M F; Varyukhina, M D; Spallone, A

    2016-07-01

    5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures. PMID:26887580

  14. Stereotactic Radiation Therapy for Benign Meningioma: Long-Term Outcome in 318 Patients

    SciTech Connect

    Fokas, Emmanouil; Henzel, Martin; Surber, Gunar; Hamm, Klaus; Engenhart-Cabillic, Rita

    2014-07-01

    Purpose: To investigate the long-term outcome of stereotactic-based radiation therapy in a large cohort of patients with benign intracranial meningiomas. Methods and Materials: Between 1997 and 2010, 318 patients with histologically confirmed (44.7%; previous surgery) or imaging-defined (55.3%) benign meningiomas were treated with either fractionated stereotactic radiation therapy (79.6%), hypofractionated stereotactic radiation therapy (15.4%), or stereotactic radiosurgery (5.0%), depending on tumor size and location. Local control (LC), overall survival (OS), cause-specific survival (CSS), prognostic factors, and toxicity were analyzed. Results: The median follow-up was 50 months (range, 12-167 months). Local control, OS, and CSS at 5 years were 92.9%, 88.7%, and 97.2%, and at 10 years they were 87.5%, 74.1%, and 97.2%, respectively. In the multivariate analysis, tumor location (P=.029) and age >66 years (P=.031) were predictors of LC and OS, respectively. Worsening of pre-existing neurologic symptoms immediately after radiation therapy occurred in up to 2%. Clinically significant acute toxicity (grade 3°) occurred in 3%. Only grade 1-2 late toxicity was observed in 12%, whereas no new neurologic deficits or treatment-related mortality were encountered. Conclusions: Patients with benign meningiomas predominantly treated with standard fractionated stereotactic radiation therapy with narrow margins enjoy excellent LC and CSS, with minimal long-term morbidity.

  15. Primary leptomeningeal melanoma of the cervical spine mimicking a meningioma-a case report.

    PubMed

    Marx, Sascha; Fleck, Steffen K; Manwaring, Jotham; Vogelgesang, Silke; Langner, Soenke; Schroeder, Henry W S

    2014-08-01

    Background and Importance Primary leptomeningeal melanoma (PLM) is highly malignant and exceedingly rare. Due to its rarity, diagnostic and treatment paradigms have been slow to evolve. We report the first case of a PLM that mimics a cervical spine meningioma and then discuss the current clinical, radiologic, and pathologic diagnostic methodologies as well as expected outcomes related to this disease. Clinical Presentation A 54-year-old woman presented a dural-based extramedullary solid mass ventral to the C2-C3 spinal cord causing spinal cord compression without cord signal changes, characteristic of meningioma. Intraoperative microscopic inspection revealed numerous black spots littering the surface of the dura; the tumor itself was yellow in appearance and had a soft consistency. Pathologic analysis of the specimen revealed a malignant melanin-containing tumor. No primary site was found, so a diagnosis of primary leptomeningeal melanoma was made, and the patient subsequently received interferon therapy. To date (2 years postoperatively), no local or systemic recurrence of the tumor has been identified. Conclusion As with most rare tumors, case reports constitute the vast majority of references to PLM. Only an increased awareness and an extensive report of each individual case can help diagnose and clarify the nature of PLM. Clinicians need to be aware of such malignant conditions when diagnosing benign tumoral lesions of the spine such as meningiomas. PMID:25083399

  16. Minimally Invasive Supraorbital Key-hole Approach for the Treatment of Anterior Cranial Fossa Meningiomas

    PubMed Central

    IACOANGELI, Maurizio; NOCCHI, Niccolò; NASI, Davide; DI RIENZO, Alessandro; DOBRAN, Mauro; GLADI, Maurizio; COLASANTI, Roberto; ALVARO, Lorenzo; POLONARA, Gabriele; SCERRATI, Massimo

    2016-01-01

    The most important target of minimally invasive surgery is to obtain the best therapeutic effect with the least iatrogenic injury. In this background, a pivotal role in contemporary neurosurgery is played by the supraorbital key-hole approach proposed by Perneczky for anterior cranial base surgery. In this article, it is presented as a possible valid alternative to the traditional craniotomies in anterior cranial fossa meningiomas removal. From January 2008 to January 2012 at our department 56 patients underwent anterior cranial base meningiomas removal. Thirty-three patients were submitted to traditional approaches while 23 to supraorbital key-hole technique. A clinical and neuroradiological pre- and postoperative evaluation were performed, with attention to eventual complications, length of surgical procedure, and hospitalization. Compared to traditional approaches the supraorbital key-hole approach was associated neither to a greater range of postoperative complications nor to a longer surgical procedure and hospitalization while permitting the same lesion control. With this technique, minimization of brain exposition and manipulation with reduction of unwanted iatrogenic injuries, neurovascular structures preservation, and a better aesthetic result are possible. The supraorbital key-hole approach according to Perneckzy could represent a valid alternative to traditional approaches in anterior cranial base meningiomas surgery. PMID:26804334

  17. Factors Associated with Low Socioeconomic Status Predict Poor Postoperative Follow-up after Meningioma Resection.

    PubMed

    Nayeri, Arash; Brinson, Philip R; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola B

    2016-06-01

    Objectives To quantify the rates of loss of follow-up after meningioma resection and to identify any key demographical associations. Design Retrospective cohort. Setting Vanderbilt University Medical Center, 2001-2013. Participants A total of 281 patients surgically treated for an intracranial meningioma at a single institution between 2001 and 2013. Main Outcome Measures Patient clinical follow-up within the first postoperative year. Results A history of tobacco use (p < 0.0001), ongoing alcohol abuse at time of presentation (p = 0.0014), Medicaid coverage (p < 0.0001), and lack of a college degree (p < 0.0001) were all found to be predictors of loss of follow-up at a statistically significant level. Conclusions Several factors associated with low socioeconomic status are predictors of poor clinical follow-up after meningioma resection. The health risk of poor follow-up in this patient population is significant, and increased measures are needed to ensure regular appointment attendance. PMID:27175317

  18. Primary extramedullary spinal melanoma mimicking spinal meningioma: A case report and literature review

    PubMed Central

    LI, YU-PING; ZHANG, HENG-ZHU; SHE, LEI; WANG, XIAO-DONG; DONG, LUN; XU, ENXI; WANG, XING-DONG

    2014-01-01

    Primary spinal melanoma is a rare lesion, which occurs throughout the cranial and spinal regions, however, is primarily observed in the middle or lower thoracic spine. The clinical features of primary spinal melanoma are complex and unspecific, resulting in a high misdiagnosis rate. In the present case report, a rare case of spinal melanoma exhibiting the dural tail sign and mimicking spinal meningioma is reported. The initial diagnosis, using magnetic resonance imaging (MRI), was unclear. Thus, melanin-containing tumors and spinal meningioma should have been considered in the differential diagnosis. The tumor was completely resected using a standard posterior midline approach, which was followed by chemotherapy. Subsequent to the surgery, the patient was discharged with improved motor capacity and a follow-up MRI scan showed no recurrence after six months. The present study demonstrates that it is critical for neurosurgeons to focus on increasing the accuracy of initial diagnoses in order to make informed decisions regarding the requirement for surgical resection. The present case report presents the clinical, radiological and pathological features of primary extramedullary spinal melanoma mimicking spinal meningioma to emphasize the importance of early identification and diagnosis. PMID:24959273

  19. Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.

    PubMed

    Thürling, Markus; Kahl, Fabian; Maderwald, Stefan; Stefanescu, Roxana M; Schlamann, Marc; Boele, Henk-Jan; De Zeeuw, Chris I; Diedrichsen, Jörn; Ladd, Mark E; Koekkoek, Sebastiaan K E; Timmann, Dagmar

    2015-01-21

    There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded. PMID:25609637

  20. Invasive Ponto-Caspian hydrozoan Cordylophora caspia (hydrozoa: Cnidaria) in southern Baltic coastal lakes

    NASA Astrophysics Data System (ADS)

    Obolewski, Krystian; Jarosiewicz, Anna; Ożgo, Małgorzata

    2015-12-01

    Cordylophora caspia Pall. is a highly invasive Ponto-Caspian colonial hydroid with a worldwide distribution. It is a biofouling organism colonizing industrial water installations and causing serious economic problems. Here, we give the first report of its occurrence in southern Baltic coastal lakes, and analyze its distribution in relation to environmental factors and likely colonization routes. Samples were collected from the stalks of Phragmites australis at the total of 102 sites in 15 lakes and lagoons. The species was most numerous in lagoons, i.e. ß-oligohaline water bodies with a surface hydrological connection with the sea, where it reached mean densities of 1200-4800 hydranths m-2. In regression tree analysis, chloride concentration, followed by pH, were the strongest explanatory variables for its occurrence, with highest densities observed at chloride concentration above 1.18 g Cl L-1 and pH 8.05-9.26. At pH 5.77-8.04 higher densities were observed at temperatures above 20.3 °C. Generally, within the range of parameters observed in our study, high densities of C. caspia were associated with high chloride concentration, pH, temperature and electrical conductivity values. The species was also present in freshwater lakes; these colonies may have the highest capacity for future invasions of such habitats. Within lakes, high densities were observed at canals connecting these water bodies with the sea, and at sites close to the inflow of rivers. This distribution pattern can facilitate its further spread into inland waters.

  1. Proteomic analysis of native cerebellar iFGF14 complexes.

    PubMed

    Bosch, Marie K; Nerbonne, Jeanne M; Townsend, R Reid; Miyazaki, Haruko; Nukina, Nobuyuki; Ornitz, David M; Marionneau, Céline

    2016-07-01

    Intracellular Fibroblast Growth Factor 14 (iFGF14) and the other intracellular FGFs (iFGF11-13) regulate the properties and densities of voltage-gated neuronal and cardiac Na(+) (Nav) channels. Recent studies have demonstrated that the iFGFs can also regulate native voltage-gated Ca(2+) (Cav) channels. In the present study, a mass spectrometry (MS)-based proteomic approach was used to identify the components of native cerebellar iFGF14 complexes. Using an anti-iFGF14 antibody, native iFGF14 complexes were immunoprecipitated from wild type adult mouse cerebellum. Parallel control experiments were performed on cerebellar proteins isolated from mice (Fgf14(-/-)) harboring a targeted disruption of the Fgf14 locus. MS analyses of immunoprecipitated proteins demonstrated that the vast majority of proteins identified in native cerebellar iFGF14 complexes are Nav channel pore-forming (α) subunits or proteins previously reported to interact with Nav α subunits. In contrast, no Cav channel α or accessory subunits were revealed in cerebellar iFGF14 immunoprecipitates. Additional experiments were completed using an anti-PanNav antibody to immunoprecipitate Nav channel complexes from wild type and Fgf14(-/-) mouse cerebellum. Western blot and MS analyses revealed that the loss of iFGF14 does not measurably affect the protein composition or the relative abundance of Nav channel interacting proteins in native adult mouse cerebellar Nav channel complexes. PMID:26889602

  2. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    SciTech Connect

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  3. Motor learning of mice lacking cerebellar Purkinje cells.

    PubMed

    Porras-García, M Elena; Ruiz, Rocío; Pérez-Villegas, Eva M; Armengol, José Á

    2013-01-01

    The cerebellum plays a key role in the acquisition and execution of motor tasks whose physiological foundations were postulated on Purkinje cells' long-term depression (LTD). Numerous research efforts have been focused on understanding the cerebellum as a site of learning and/or memory storage. However, the controversy on which part of the cerebellum participates in motor learning, and how the process takes place, remains unsolved. In fact, it has been suggested that cerebellar cortex, deep cerebellar nuclei, and/or their combination with some brain structures other than the cerebellum are responsible for motor learning. Different experimental approaches have been used to tackle this question (cerebellar lesions, pharmacological agonist and/or antagonist of cerebellar neurotransmitters, virus tract tracings, etc.). One of these approaches is the study of spontaneous mutations affecting the cerebellar cortex and depriving it of its main input-output organizer (i.e., the Purkinje cell). In this review, we discuss the results obtained in our laboratory in motor learning of both Lurcher (Lc/+) and tambaleante (tbl/tbl) mice as models of Purkinje-cell-devoid cerebellum. PMID:23630472

  4. Motor learning of mice lacking cerebellar Purkinje cells

    PubMed Central

    Porras-García, M. Elena; Ruiz, Rocío; Pérez-Villegas, Eva M.; Armengol, José Á.

    2013-01-01

    The cerebellum plays a key role in the acquisition and execution of motor tasks whose physiological foundations were postulated on Purkinje cells' long-term depression (LTD). Numerous research efforts have been focused on understanding the cerebellum as a site of learning and/or memory storage. However, the controversy on which part of the cerebellum participates in motor learning, and how the process takes place, remains unsolved. In fact, it has been suggested that cerebellar cortex, deep cerebellar nuclei, and/or their combination with some brain structures other than the cerebellum are responsible for motor learning. Different experimental approaches have been used to tackle this question (cerebellar lesions, pharmacological agonist and/or antagonist of cerebellar neurotransmitters, virus tract tracings, etc.). One of these approaches is the study of spontaneous mutations affecting the cerebellar cortex and depriving it of its main input–output organizer (i.e., the Purkinje cell). In this review, we discuss the results obtained in our laboratory in motor learning of both Lurcher (Lc/+) and tambaleante (tbl/tbl) mice as models of Purkinje-cell-devoid cerebellum. PMID:23630472

  5. Mitotic Events in Cerebellar Granule Progenitor Cells that Expand Cerebellar Surface Area Are Critical for Normal Cerebellar Cortical Lamination in Mice

    PubMed Central

    Chang, Joshua C.; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier

    2015-01-01

    Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereological principles. We demonstrate that during the proliferative phase of the external granule layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding either 2 cells in the same layer to increase surface area (β-events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α-events). As the cerebellum grows, therefore, β-events lie upstream of α-events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify inter-mitotic times for β-events on a per-cell basis in post-natal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereological studies. PMID:25668568

  6. Presynaptic Calcium Signalling in Cerebellar Mossy Fibres

    PubMed Central

    Thomsen, Louiza B.; Jörntell, Henrik; Midtgaard, Jens

    2009-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na+ spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette. PMID:20162034

  7. Linac-based stereotactic radiotherapy and radiosurgery in patients with meningioma

    PubMed Central

    2014-01-01

    Background It was our purpose to analyze long-term clinical outcome and to identify prognostic factors after Linac-based fractionated stereotactic radiotherapy (Linac-based FSRT) and stereotactic radiosurgery (SRS) in patients with intracranial meningiomas. Materials and methods Between 10/1995 and 03/2009, 297 patients with a median age of 59 years were treated with FSRT for intracranial meningioma. 50 patients had a Grade I meningioma, 20 patients had a Grade II meningioma, 12 patients suffered from a Grade III tumor, and in 215 cases no histology was obtained (Grade 0). Of the 297 patients, 144 underwent FSRT as their primary treatment and 158 underwent postoperative FSRT. 179 patients received normofractionated radiotherapy (nFSRT), 92 patients received hypofractionated FSRT (hFSRT) and 26 patients underwent SRS. Patients with nFSRT received a mean total dose of 57.31 ± 5.82 Gy, patients with hFSRT received a mean total dose of 37.6 ± 4.4 Gy and patients who underwent SRS received a mean total dose of 17.31 ± 2.58 Gy. Results Median follow-up was 35 months. Overall progression free survival (PFS) was 92.3% at 3 years, 87% at 5 years and 84.1% at 10 years. Patients with adjuvant radiotherapy showed significantly better PFS-rates than patients who had been treated with primary radiotherapy. There was no significant difference between PFS-rates of nFSRT, hFSRT and SRS patients. PFS-rates were independent of tumor size. Patients who had received nFSRT showed less acute toxicity than those who had received hFSRT. In the Grade 0/I group the rate of radiologic focal reactions was significantly lower than in the atypical/malignant histology group. Conclusion This large study showed that FSRT is an effective and safe treatment modality with high PFS-rates for intracranial meningioma. We identified “pathological grading” and and “prior surgery” as significant prognostic factors. PMID:24650090

  8. Combined Proton and Photon Conformal Radiotherapy for Intracranial Atypical and Malignant Meningioma

    SciTech Connect

    Boskos, Christos Feuvret, Loic; Noel, Georges; Habrand, Jean-Louis; Pommier, Pascal; Alapetite, Claire; Mammar, Hamid; Ferrand, Regis; Boisserie, Gilbert; Mazeron, Jean-Jacques

    2009-10-01

    Purpose: To evaluate retrospectively the efficacy of conformal fractionated radiotherapy combining proton and photon beams after primary surgery for treatment of atypical and malignant meningiomas. Patients and Methods: Between September 1999 and October 2006, 24 patients (12 male, 12 female) with histopathologically proven meningioma (atypical 19, malignant 5) received postoperative combined radiotherapy with a 201-MeV proton beam at the Centre Protontherapie d'Orsay and a high-energy photon beam. Six patients underwent gross total resection and 18 a subtotal resection. Median gross tumor volume and clinical target volume were 44.7 cm{sup 3} and 153.3 cm{sup 3}, respectively. Mean total irradiation dose was 65.01 CGE (cobalt gray equivalent), with a mean proton total dose of 34.05 CGE and a mean photon total dose 30.96 CGE. Results: The median (range) follow-up interval was 32.2 (1-72) months. The overall mean local relapse-free interval was 27.2 (10-50) months, 28.3 (10-50) months for atypical meningioma and 23 (13-33) months for malignant meningioma. Ten tumors recurred locally. One-, 2-, 3-, 4-, 5-, and 8- year local control rates for the entire group of patients were 82.9% {+-} 7.8%, 82.9% {+-} 7.8%, 61.3% {+-} 11%, 61.3% {+-} 11%, 46.7% {+-} 12.3%, and 46.7% {+-} 12.3%, respectively. One-, 2-, 3-, 4-, 5-, and 8- year overall survival rates were 100%, 95.5% {+-} 4.4%, 80.4% {+-} 8.8%, 65.3% {+-} 10.6%, 53.2% {+-} 11.6%, and 42.6% {+-} 13%, respectively. Survival was significantly associated with total dose. There was no acute morbidity of radiotherapy. One patient developed radiation necrosis 16 months after treatment. Conclusions: Postoperative combination of conformal radiotherapy with protons and photons for atypical and malignant meningiomas is a well-tolerated treatment producing long-term tumor stabilization.

  9. Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.

    PubMed

    Velpula, Kiran Kumar; Gogineni, Venkateswara Rao; Nalla, Arun Kumar; Dinh, Dzung H; Rao, Jasti S

    2013-02-01

    Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H(2)O(2) or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers u

  10. Radiation-Induced Hypomethylation Triggers Urokinase Plasminogen Activator Transcription in Meningioma Cells1

    PubMed Central

    Velpula, Kiran Kumar; Gogineni, Venkateswara Rao; Nalla, Arun Kumar; Dinh, Dzung H; Rao, Jasti S

    2013-01-01

    Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H2O2 or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers u

  11. Meninigiomas of the Craniocervical Junction – A Distinctive Subgroup of Meningiomas

    PubMed Central

    Dührsen, Lasse; Emami, Pedram; Matschke, Jakob; Abboud, Tammam; Westphal, Manfred; Regelsberger, Jan

    2016-01-01

    Objective Meningioma of the cranio-cervical junction is a rare diagnosis and demand a thorough surgical planning as radical excision of these tumors is difficult. In this context recurrence is most likely due to regrowth of residual tumor. The aim of this study was to evaluate the clinical course of patients operated for craniocervical meningioma (CCM) and to investigate the histological features of these tumors and their impact on recurrence rate. Methods All patients who were operated for CCM at our institution between 2003 and 2012 were identified. Presenting symptoms, MRI findings, surgical approaches and recurrence rate were reviewed retrospectively using medical charts. Histological features of the included tumors were studied focusing on subtypes and MIB-1 immunoreactivity and compared with MIB-1 immunoreactivity in an age and gender-matched control group of patients with supratentorial meningioma. Results 18 patients with CCM with a mean age of 56.2 years and median follow-up of 60 months were included in the study. Sensory or motor deficit was the most frequent presenting symptom followed by neck pain and lower cranial nerve palsy. Simpson grade II resection was achieved in 16 patients and Simpson grade III resection in two patients. Mortality, morbidity and recurrence rates were 16.7%, 5.5% and 5.5%, respectively. According to the WHO-grading all were found to be grade I meningiomas. Histological subtypes included meningotheliomatous (10), transitional (2), fibrillar (2), angiomatous (3) and secretory (1) meningioma. The mean MIB-1 labeling index in the study group was significantly higher than in the control group, (7.2% and 3.6%, respectively), p < 0.05. There was no correlation between MIB-1 levels and tumor recurrence. Conclusions CCM seems to have a benign character. Despite a significantly higher MIB-1 index, a high rate of recurrence was not observed. Therefore, approaches with high morbidity are not justified. Nevertheless, in view of the

  12. Sphenoidal pneumosinus dilatans due to anterior skull base meningiomas - CT and MRI aspects: Report of two new cases and literature review.

    PubMed

    Scuotto, Assunta; Saracino, Dario; Rotondo, Michele; Izzo, Andrea; Urraro, Fabrizio; Cappabianca, Salvatore; Sampaolo, Simone

    2016-08-01

    We report on two patients disclosing a pneumosinus dilatans (PSD) and an anterior skull base meningioma. Our findings, together with those from the pertinent literature, support the thought that this infrequent anomaly of paranasal sinuses is a useful clue to suspect a concomitant meningioma. Moreover, hypotheses concerning the pathophysiology of PSD are discussed. PMID:27220845

  13. Early Childhood Obesity is Associated with Compromised Cerebellar Development

    PubMed Central

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS — a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric MRI images. Individuals with PWS (n=16) and EMO (n=12) had smaller cerebellar volumes than a control group of 15 siblings (p=0.02 control vs. EMO; p=0.0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 ± 25; EMO 81 ± 19; and Controls 112 ± 13 (p<0.0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development. PMID:19437203

  14. Behavioral effects of neonatal lesions on the cerebellar system.

    PubMed

    Lalonde, Robert; Strazielle, Catherine

    2015-06-01

    Several rodent models with spontaneous mutations causing cerebellar pathology are impaired in motor functions during the neonatal period, including Grid2(Lc), Rora(sg), Dab1(scm), Girk2(Wv), Lmx1a(dr-sst), Myo5a(dn), Inpp4a(wbl), and Cacna1a(rol) mice as well as shaker and dystonic rats. Deficits are also evident in murine null mutants such as Zic1, Fgfr1/FgFr2, and Xpa/Ercc8. Behavioral deficits are time-dependent following X-irradiated- or aspiration-induced lesions of the cerebellum in rats. In addition, motor functions are deficient after lesions in cerebellar-related pathways. As in animal subjects, sensorimotor disturbances have been described in children with cerebellar lesions. These results underline the importance of the cerebellum and its connections in the development of motor functions. PMID:25907855

  15. Cerebellar networks with the cerebral cortex and basal ganglia.

    PubMed

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2013-05-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent findings from neuroanatomical, behavioral, and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that cerebellar output reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, which suggests that the two subcortical structures are part of a densely interconnected network. Taken together, these findings elucidate the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  16. Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

    PubMed Central

    Gao, Zhenyu; Proietti-Onori, Martina; Lin, Zhanmin; ten Brinke, Michiel M.; Boele, Henk-Jan; Potters, Jan-Willem; Ruigrok, Tom J.H.; Hoebeek, Freek E.; De Zeeuw, Chris I.

    2016-01-01

    Summary Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning. PMID:26844836

  17. Cytomorphology of Recurrent Osseous Extracranial Meningioma of Right Pubic Ramus:: Report of a Case and Literature Review.

    PubMed

    Bokhari, Aqiba; Hibshoosh, Hanina; Tiscornia-Wasserman, Patricia G

    2016-07-01

    Meningiomas are well-recognized neoplasms of the central nervous system. Primary extracranial meningiomas (ECMs) are extremely rare and arise in various anatomic sites. We present a 56-year-old female with 13-year history of primary grade I meningothelial meningioma of right pubic symphysis, orthotopic heart transplant, and right total hip arthroplasty, who presented with progressive right hip pain for 3 weeks. Primary intracranial, intraspinal and other tumors were excluded. Imaging revealed a destructive lytic lesion at right superior and inferior pubic rami and body, associated with extensive bone destruction and soft tissue mass. Touch imprint (TI) cytology of computed tomography (CT)-guided core biopsy from the right pubic ramus (PRA) lesion showed a spindle cell neoplasm, with classical syncytial, lobular, and whorling cellular arrangement, composed of spindle, oval or round nuclei with occasional pseudoinclusions, consistent with known history of osseous meningioma. Tumor was further characterized by histopathology as grade 1 meningioma with meningothelial features. To our knowledge, primary osseous ECM arising specifically at the PRA has not been reported previously. ECM at this site may pose a diagnostic challenge for cytologists as its features may resemble other more commonly observed lesions. Accurate diagnosis requires awareness of occurrence of ECM at PRA and recognition of its characteristic cytomorphology. TI cytological features of our case are presented and previously described cytology of ECMs and diagnostic pitfalls are reviewed. Diagn. Cytopathol. 2016;44:618-622. © 2016 Wiley Periodicals, Inc. PMID:27079302

  18. The effects of PK11195 on meningioma was associated with allopregnanolone biosynthesis, which was mediated by translocator protein 18 KDa.

    PubMed

    Gao, Zhuo-Wei; Huang, Jing-Bin; Lin, Qing; Qin, Qiang; Liang, Yao-Jun; Zhou, Lu; Luo, Min

    2016-01-01

    Meningioma is one of the common brain tumors in adults. It had been shown that the allopregnanolone biosynthesis was associated with tumorigenesis and PK11195, the translocator protein 18 KDa (TSPO) antagonist, had the effects of the allopregnanolone biosynthesis. However, little is known about the association between the effects of PK11195 on meningioma and the allopregnanolone biosynthesis. To evaluate this, the meningioma cell line IOMM-LEE was applied. Cell viability and proliferation were determined by CCK-8 assay. The IC50 of PK11195 on the IOMM-LEE was 1.505 ± 0.08 nM. The cell viability and proliferation of AC-5216 (TSPO selective ligand, 2 and 4 nM) was blocked by PK11195 (1.5 nM). Further, we evaluated the role of allopregnanolone biosynthesis in the effects of TSPO on meningioma. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the allopregnanolone level. It showed that the allopregnanolone level was increased by AC-5216 (2 and 4 nM) and the increase was reversed by PK11195 (1.5 nM). Collectedly, it firstly indicated that the effects of PK11195 on meningioma were relevant to the decrease of allopregnanolone biosynthesis, which was mediated by TSPO. PMID:26835706

  19. Spontaneous, synchronized, and corrective timing behavior in cerebellar lesion patients.

    PubMed

    Schwartze, Michael; Keller, Peter E; Kotz, Sonja A

    2016-10-01

    To successfully navigate through and interact with a dynamic environment it is necessary to acquire and use adequate temporal information to guide behavior. Apart from several areas in the cerebral cortex and cortico-striatal networks, the cerebellum has been proposed to engage in the processing of temporal information. Damage to the cerebellum can impair precise event-based temporal processing in motor and non-motor behavior. To further substantiate cerebellar contributions to temporal processing and to explore its specific role in adapting to a dynamic environment, we investigated sensorimotor temporal processing in ten patients with cerebellar lesions and a corresponding number of healthy matched controls. Experimental tasks included simple self-paced repetitive finger-tapping (spontaneous motor tempo), temporally non-adaptive (isochronous pacing) and adaptive (tempo-changing pacing) sensorimotor synchronization with auditory sequences (synchronization-continuation tapping), and a perceptual tempo judgment. The results indicate that patients' performance diverges systematically from controls on several measures. Cerebellar patients demonstrate more variable self-paced tapping, larger negative asynchronies when synchronizing with isochronous pacing sequences, altered automatic error correction responses to tempo changes (phase correction), and decreased perceptual sensitivity to these perturbations, especially for small accelerations. These findings confirm imprecise temporal processing in cerebellar patients, and hint at a specific impairment in the tens-of-milliseconds range preceding critical events, in line with a temporally predictive account of cerebellar function. Moreover, this cerebellar profile complements previous findings concerning dysfunctional temporal processing in basal ganglia patients assessed with the same experimental setup, suggesting structural and functional differentiation within an integrative temporal processing network. PMID:27345424

  20. Modulatory Effects of Theta Burst Stimulation on Cerebellar Nonsomatic Functions

    PubMed Central

    Demirtas-Tatlidede, Asli; Freitas, Catarina; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.

    2011-01-01

    Clinical and functional imaging studies suggest that the cerebellar vermis is involved in the regulation of a range of nonsomatic functions including cardiovascular control, thirst, feeding behavior, and primal emotions. Cerebello-hypothalamic circuits have been postulated to be a potential neuroanatomical substrate underlying this modulation. We tested this putative relationship between the cerebellar vermis and nonsomatic functions by stimulating the cerebellum noninvasively via neuronavigated transcranial magnetic stimulation. In this randomized, counter-balanced, within-subject study, intermittent theta burst stimulation (TBS) was applied on three different days to the vermis and the right and left cerebellar hemispheres of 12 right-handed normal subjects with the aim of modulating activity in the targeted cerebellar structure. TBS-associated changes were investigated via cardiovascular monitoring, a series of emotionally arousing picture stimuli, subjective analog scales for primal emotions, and the Profile of Mood States test. All 36 sessions of cerebellar stimulation were tolerated well without serious adverse events. Cardiovascular monitoring pointed to a mild but significant decrease in heart rate subsequent to vermal stimulation; no changes were detected in systolic or diastolic blood pressure measurements. Subjective ratings detected a significant increase in Thirst and a trend toward increased Appetite following vermal stimulation. These observations are consistent with existing neurophysiological and neuroimaging data indicating a role for the cerebellum in the regulation of visceral responses. In conjunction with the modulatory function of the cerebellum, our results suggest a role for the vermis in somatovisceral integration likely through cerebello-hypothalamic pathways. Further research is warranted to elucidate the potential mechanisms underlying the cerebellar modulation of nonsomatic functions. PMID:21132574

  1. Cerebellar substrates for error correction in motor conditioning.

    PubMed

    Gluck, M A; Allen, M T; Myers, C E; Thompson, R F

    2001-11-01

    The authors evaluate a mapping of Rescorla and Wagner's (1972) behavioral model of classical conditioning onto the cerebellar substrates for motor reflex learning and illustrate how the limitations of the Rescorla-Wagner model are just as useful as its successes for guiding the development of new psychobiological theories of learning. They postulate that the inhibitory pathway that returns conditioned response information from the cerebellar interpositus nucleus back to the inferior olive is the neural basis for the error correction learning proposed by Rescorla and Wagner (Gluck, Myers, & Thompson, 1994; Thompson, 1986). The authors' cerebellar model expects that behavioral processes described by the Rescorla-Wagner model will be localized within the cerebellum and related brain stem structures, whereas behavioral processes beyond the scope of the Rescorla-Wagner model will depend on extracerebellar structures such as the hippocampus and related cortical regions. Simulations presented here support both implications. Several novel implications of the authors' cerebellar error-correcting model are described including a recent empirical study by Kim, Krupa, and Thompson (1998), who verified that suppressing the putative error correction pathway should interfere with the Kamin (1969) blocking effect, a behavioral manifestation of error correction learning. The authors also discuss the model's implications for understanding the limits of cerebellar contributions to associative learning and how this informs our understanding of hippocampal function in conditioning. This leads to a more integrative view of the neural substrates of conditioning in which the authors' real-time circuit-level model of the cerebellum can be viewed as a generalization of the long-term memory module of Gluck and Myers' (1993) trial-level theory of cerebellar-hippocampal interaction in motor conditioning. PMID:11726240

  2. Cerebellar atrophy in a patient with velocardiofacial syndrome.

    PubMed Central

    Lynch, D R; McDonald-McGinn, D M; Zackai, E H; Emanuel, B S; Driscoll, D A; Whitaker, L A; Fischbeck, K H

    1995-01-01

    Velocardiofacial syndrome and DiGeorge syndrome have not previously been associated with central nervous system degeneration. We report a 34 year old man who presented for neurological evaluation with cerebellar atrophy of unknown aetiology. On historical review, he had neonatal hypocalcaemia, an atrial septal defect, and a corrected cleft palate. His physical examination showed the characteristic facies of velocardiofacial syndrome as well as dysmetria and dysdiadocho-kinesia consistent with cerebellar degeneration. Molecular cytogenetic studies showed a deletion of 22q11.2. This man is the first reported patient with the association of a neurodegenerative disorder and 22q11.2 deletion syndrome. Images PMID:7562973

  3. Bilateral cerebellar dysfunctions in a unilateral meso-diencephalic lesion.

    PubMed Central

    von Cramon, D

    1981-01-01

    The clinical syndrome of a 65-year-old patient with a slit-shaped right-sided meso-diencephalic lesion was analysed. A cerebellar syndrome with limb-kinetic ataxia, intention tremor and hypotonicity in all extremities as well as ataxic dysarthria was found. The disruption of the two cerebello-(rubro)-thalamic pathways probably explained the signs of bilateral cerebellar dysfunction. The uncrossed ascending limb of the right, and the crossed one of the left brachium conjunctivum may have been damaged by the unilateral lesion extending between caudal midbrain and dorsal thalamus. Images PMID:7241166

  4. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits

    PubMed Central

    Choi, Seong-Min

    2016-01-01

    Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes’ tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits. PMID:27240809

  5. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits.

    PubMed

    Choi, Seong-Min

    2016-05-01

    Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes' tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits. PMID:27240809

  6. Lactic acidosis associated with cerebellar vermal atrophy and cardiomyopathy.

    PubMed

    Challa, V R; Markesbery, W R; Baumann, R J; Noonan, J A

    1978-08-01

    The association of fluctuating neurological signs and congestive cardiomyopathy with chronic lactic acidosis is described in a 5 1/2 year-old-boy who ultimately succumbed to congestive heart failure. The autopsy findings included severe atrophy of the anterior cerebellar vermis and a hypertrophied heart with left sided endocardial fibroelastosis. Skeletal and cardial muscle calcification was prominent and probably due to the effect of intracellular metabolic alterations associated with lactic acidosis. A review of the literature shows that the combination of cardiomyopathy, isolated atrophy of cerebellar vermis and muscle fiber calcification have not been reported in association with idiopathic lactic acidosis previously. PMID:152418

  7. Inside the Thompson laboratory during the "cerebellar years" and the continuing cerebellar story.

    PubMed

    Lavond, D G; Wikgren, J; Nokia, M S

    2011-02-01

    This paper is based on the talk by one of the authors (DL) given at the symposium for the retirement of RF Thompson (RF Thompson: A bridge between 20th and 21st century neuroscience). We first make some informal observations of the historical times and research conditions in the Thompson laboratory when the cerebellum was found to play a critical role in eye lid classical conditioning, the "cerebellar years". These conditions influenced our collaborative international program on the phenomenon known as "transfer of training" or "savings". Our research shows that the appearance of "savings" is an artifact of the order of testing, and depends upon the functioning of the contralateral interpositus nucleus (IPN) in a way that is complementary to the role of the IPN in normal eyelid classical conditioning. PMID:21073973

  8. The Ponto-Caspian basin as a final trap for southeastern Scandinavian Ice-Sheet meltwater

    NASA Astrophysics Data System (ADS)

    Tudryn, Alina; Leroy, Suzanne A. G.; Toucanne, Samuel; Gibert-Brunet, Elisabeth; Tucholka, Piotr; Lavrushin, Yuri A.; Dufaure, Olivier; Miska, Serge; Bayon, Germain

    2016-09-01

    This paper provides new data on the evolution of the Caspian Sea and Black Sea from the Last Glacial Maximum until ca. 12 cal kyr BP. We present new analyses (clay mineralogy, grain-size, Nd isotopes and pollen) applied to sediments from the river terraces in the lower Volga, from the middle Caspian Sea and from the western part of the Black Sea. The results show that during the last deglaciation, the Ponto-Caspian basin collected meltwater and fine-grained sediment from the southern margin of the Scandinavian Ice Sheet (SIS) via the Dniepr and Volga Rivers. It induced the deposition of characteristic red-brownish/chocolate-coloured illite-rich sediments (Red Layers in the Black Sea and Chocolate Clays in the Caspian Sea) that originated from the Baltic Shield area according to Nd data. This general evolution, common to both seas was nevertheless differentiated over time due to the specificities of their catchment areas and due to the movement of the southern margin of the SIS. Our results indicate that in the eastern part of the East European Plain, the meltwater from the SIS margin supplied the Caspian Sea during the deglaciation until ∼13.8 cal kyr BP, and possibly from the LGM. That led to the Early Khvalynian transgressive stage(s) and Chocolate Clays deposition in the now-emerged northern flat part of the Caspian Sea (river terraces in the modern lower Volga) and in its middle basin. In the western part of the East European Plain, our results confirm the release of meltwater from the SIS margin into the Black Sea that occurred between 17.2 and 15.7 cal kyr BP, as previously proposed. Indeed, recent findings concerning the evolution of the southern margin of the SIS and the Black Sea, show that during the last deglaciation, occurred a westward release of meltwater into the North Atlantic (between ca. 20 and 16.7 cal kyr BP), and a southward one into the Black Sea (between 17.2 and 15.7 cal kyr BP). After the Red Layers/Chocolate Clays deposition in both seas

  9. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    SciTech Connect

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Debus, Juergen; Deimling, Andreas von; Hartmann, Christian

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  10. Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia

    PubMed Central

    Abbasi, Samira; Abbasi, Ataollah; Sarbaz, Yashar; Shahabi, Parviz

    2016-01-01

    Introduction: Loss of inhibitory output from Purkinje cells leads to hyperexcitability of the Deep Cerebellar Nuclei (DCN), which results in cerebellar ataxia. Also, inhibition of small-conductance calcium-activated potassium (SK) channel increases firing rate of DCN, which could cause cerebellar ataxia. Therefore, SK channel activators can be effective in reducing the symptoms of this disease, and used for the treatment of cerebellar ataxia. In this regard, we hypothesized that blockade of SK channels in different compartments of DCN would increase firing rate with different value. The location of these channels has different effects on increasing firing rate. Methods: In this study, multi-compartment computational model of DCN was used. This computational stimulation allowed us to study the changes in the firing activity of DCN neuron without concerns about interfering parameters in the experiment. Results: The simulation results demonstrated that blockade of somatic and dendritic SK channel increased the firing rate of DCN. In addition, after hyperpolarization (AHP) amplitude increased with blocking SK channel, and its regularity and resting potential changed. However, action potentials amplitude and duration had no significant changes. The simulation results illustrated a more significant contribution of SK channels on the dendritic tree to the DCN firing rate. SK channels in the proximal dendrites have more impact on firing rate compared to distal dendrites. Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels. PMID:27303600

  11. Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration.

    PubMed

    Gerwig, Marcus; Guberina, Hana; Esser, Anna Catharina; Siebler, Mario; Schoch, Beate; Frings, Markus; Kolb, Florian P; Aurich, Volker; Beck, Andreas; Forsting, Michael; Timmann, Dagmar

    2010-10-15

    The acquisition and timing of delay-conditioned eyeblink responses (CRs) have been shown to be significantly impaired in patients with disorders restricted to the cortex of the superior cerebellum. We were interested if patients improve incidences and timing of CRs across three sessions on three consecutive days. A standard delay paradigm was used in 9 patients with diffuse cerebellar degeneration, 13 patients with ischemic cortical cerebellar lesions and in 13 controls. High-resolution magnetic resonance imaging (MR imaging) was used to ensure that hemispheral lobules VI and/ or Crus I were lesioned in all stroke patients with the interposed nuclei being preserved. On day 1 patients with stroke but not with degenerative disorders showed significant CR acquisition, although total CR incidences remained significantly lower than in controls. No further improvement was visible on days 2 and 3 neither in patients with focal lesions nor in patients with cerebellar degeneration. CRs occurred earlier in cerebellar patients, most pronounced in patients with degenerative disorders. In patients with stroke but not in the degenerative group timing had improved on the third day close to values of the control subjects. Findings show that lesions of the cerebellar cortex produce permanent deficits in the acquisition of delay-conditioned eyeblink responses. Overall, mean CR incidence was higher in focal compared to degenerative disorders, most likely because the critical lobules (VI and Crus I) were lesioned only in part. Intact anterior lobe, which it thought to contribute to CR timing, may explain recovery of disordered timing in focal cerebellar patients. PMID:20385171

  12. (68)Ga-DOTANOC PET/CT detection of multiple extracranial localizations in a patient with anaplastic meningioma.

    PubMed

    Golemi, A; Ambrosini, A; Cecchi, P; Ruiu, A; Chondrogiannis, S; Farsad, M; Rubello, D

    2015-01-01

    We report herein a case of a 65-year-old male with intracranial recurrence of atypical meningioma initially treated with a combination of surgical resection and gamma knife radiotherapy. Afterwards, he underwent a (68)Ga-DOTANOC PET/CT scan in order to evaluate the feasibility of peptide receptor radionuclide therapy (PRRT). The scan identified multiple pulmonary, pleural and lymph node localizations. Histological diagnosis was consistent with intracranial atypical meningioma with diffuse metastatic spread. In our case, we have shown that meningioma with extracranial locations may present high uptake of somatostatin receptor analogues. Among other radionuclides, we believe that (68)Ga-DOTANOC PET/CT may be particularly useful for staging, detection of recurrence, evaluation of disease extension and alternative therapeutic approaches. PMID:25890891

  13. In vitro testing to a panel of potential chemotherapeutics and current concepts of chemotherapy in benign meningiomas.

    PubMed

    Balik, Vladimir; Sulla, Igor; Park, Hun Ho; Sarissky, Marek

    2015-09-01

    Treatment of benign meningiomas remains a challenge, especially when they involve the skull-base or when surgery and radiation fail. Moreover, a recent in vitro MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) study testing hydroxyurea, temozolomide and other targeting agents failed to identify drugs effective in their treatment; therefore the search for further more effective agents continues. We performed a thorough review of in vitro investigations, animal studies and human clinical trials and endeavoured to integrate our results of MTT assay into current concepts of chemotherapy in benign meningiomas. Our results demonstrated that other chemotherapeutics with various mechanisms of action have the potential to be incorporated into second line therapy. Our study shows for the first time that chemosensitivity/resistance may be associated with histopathological variants of benign meningiomas. PMID:26099192

  14. Cerebellar ataxia as a possible complication of babesiosis in two dogs.

    PubMed

    Jacobson, L S

    1994-09-01

    A 6-month-old Miniature Doberman Pinscher was presented with inappetance and cerebellar signs. Babesia canis organisms were found on a capillary bloodsmear. The cerebellar signs resolved rapidly following treatment with diminazene aceturate. A 7-month-old Siberian Husky developed cerebellar signs, blindness and quadriparesis 9 d after presentation with clinical signs typical of uncomplicated canine babesiosis. The dog responded favourably to treatment with prednisolone. Both acute and delayed cerebellar ataxia have been associated with malaria in humans. The clinical signs shown by these dogs were similar to those reported for malaria in humans. Cerebellar ataxia should be considered a possible complication of canine babesiosis. PMID:7595921

  15. Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence

    PubMed Central

    Ongaratti, B.R.; Silva, C.B.O.; Trott, G.; Haag, T.; Leães, C.G.S.; Ferreira, N.P.; Oliveira, M.C.; Pereira-Lima, J.F.S.

    2016-01-01

    Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2±12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83±11.60) and grades II and III (46.58±15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth. PMID:27007654

  16. Outcome of resection of WHO Grade II meningioma and correlation of pathological and radiological predictive factors for recurrence.

    PubMed

    Nanda, Anil; Bir, Shyamal C; Konar, Subhas; Maiti, Tanmoy; Kalakoti, Piyush; Jacobsohn, Jamie A; Guthikonda, Bharat

    2016-09-01

    This study investigated whether extent of surgical resection (Simpson and Shinshu grade) along with pathological and radiological factors influence the tumor control and recurrence-free survival (RFS) of patients with World Health Organization (WHO) grade II meningiomas. The clinical, radiological and surgical notes on the 59 patients with WHO grade II meningioma managed at our institution over 20years were retrospectively reviewed. In this study, median survival time was 41months. The overall recurrence rate in Simpson grades I and II resection was 31%. In grades III and IV, the overall recurrence rate was 73%, and this high recurrence rate in these groups was confined within 5years. In Cox regression analysis, combined data of grades (I and II)/complete resection showed a significant difference in RFS compared to grades (III and IV)/subtotal resection (p=0.0001). A similar trend of RFS (p=0.0001) was observed with the Shinshu grading system of resection. In addition, a Ki-67% marker for proliferation less than 15% (p=0.029), absence of certain radiological features including heterogeneous enhancement, cyst formation and peritumoral edema (p=0.006), and repeat surgery for recurrent meningioma was associated with better survival (p=0.014). However, radiosurgery did not have a beneficial role in the treatment of recurrence of atypical meningioma. The Simpson grading system is the primary predictor of recurrence of WHO grade II meningioma after resection. In addition, certain pathological and radiological features need to be considered as possible factors of recurrence after resection. Lastly, depending on the likely risks and surgical morbidity, repeat surgical resection should be performed for recurrent atypical meningioma. PMID:27427214

  17. Cerebellar Damage Produces Selective Deficits in Verbal Working Memory

    ERIC Educational Resources Information Center

    Ravizza, Susan M.; Mccormick, Cristin A.; Schlerf, John E.; Justus, Timothy; Ivry, Richard B.; Fiez, Julie A.

    2006-01-01

    The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The…

  18. Neurodevelopmental Outcomes in Children with Cerebellar Malformations: A Systematic Review

    ERIC Educational Resources Information Center

    Bolduc, Marie-Eve; Limperopoulos, Catherine

    2009-01-01

    Cerebellar malformations are increasingly diagnosed in the fetal period. Consequently, their consideration requires stressful and often critical decisions from both clinicians and families. This has resulted in an emergent need to understand better the impact of these early life lesions on child development. We performed a comprehensive literature…

  19. Verb Generation in Children and Adolescents with Acute Cerebellar Lesions

    ERIC Educational Resources Information Center

    Frank, B.; Schoch, B.; Hein-Kropp, C.; Dimitrova, A.; Hovel, M.; Ziegler, W.; Gizewski, E. R.; Timmann, D.

    2007-01-01

    The aim of the present study was to examine verb generation in a larger group of children and adolescents with acute focal lesions of the cerebellum. Nine children and adolescents with cerebellar tumours participated. Subjects were tested a few days after tumour surgery. For comparison, a subgroup was tested also 1 or 2 days before surgery. None…

  20. Predicting and correcting ataxia using a model of cerebellar function

    PubMed Central

    Bhanpuri, Nasir H.; Okamura, Allison M.

    2014-01-01

    Cerebellar damage results in uncoordinated, variable and dysmetric movements known as ataxia. Here we show that we can reliably model single-joint reaching trajectories of patients (n = 10), reproduce patient-like deficits in the behaviour of controls (n = 11), and apply patient-specific compensations that improve reaching accuracy (P < 0.02). Our approach was motivated by the theory that the cerebellum is essential for updating and/or storing an internal dynamic model that relates motor commands to changes in body state (e.g. arm position and velocity). We hypothesized that cerebellar damage causes a mismatch between the brain’s modelled dynamics and the actual body dynamics, resulting in ataxia. We used both behavioural and computational approaches to demonstrate that specific cerebellar patient deficits result from biased internal models. Our results strongly support the idea that an intact cerebellum is critical for maintaining accurate internal models of dynamics. Importantly, we demonstrate how subject-specific compensation can improve movement in cerebellar patients, who are notoriously unresponsive to treatment. PMID:24812203

  1. Cortical networks of procedural learning: evidence from cerebellar damage.

    PubMed

    Torriero, Sara; Oliveri, Massimiliano; Koch, Giacomo; Lo Gerfo, Emanuele; Salerno, Silvia; Petrosini, Laura; Caltagirone, Carlo

    2007-03-25

    The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitive transcranial magnetic stimulation (rTMS). Although inhibition of the right DLPFC or a control fronto-parietal region did not modify the patient's performance, inhibition of the right (unaffected) cerebellum and the left DLPFC markedly improved task performance. These findings could be explained by the modulation of a set of inhibitory and excitatory connections between the lateral cerebellum and the contralateral prefrontal area induced by rTMS. The presence of left cerebellar damage is likely associated with a reduced excitatory drive from sub-cortical left cerebellar nuclei towards the right DLPFC, causing reduced excitability of the right DLPFC and, conversely, unbalanced activation of the left DLPFC. Inhibition of the left DLPFC would reduce the unbalancing of cortical activation, thus explaining the observed selective recovery of procedural memory. PMID:17166525

  2. Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.

    PubMed

    Falcon, M I; Gomez, C M; Chen, E E; Shereen, A; Solodkin, A

    2016-07-01

    Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies. PMID:26209844

  3. Cerebellar Zonal Patterning Relies on Purkinje Cell Neurotransmission

    PubMed Central

    White, Joshua J.; Arancillo, Marife; Stay, Trace L.; George-Jones, Nicholas A.; Levy, Sabrina L.; Heck, Detlef H.

    2014-01-01

    Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. The proper connectivity of zones is critical for motor coordination and motor learning, and in several neurological diseases cerebellar circuits degenerate in zonal patterns. Despite recent advances in understanding zone function, we still have a limited understanding of how zones are formed. Here, we focused our attention on Purkinje cells to gain a better understanding of their specific role in establishing zonal circuits. We used conditional mouse genetics to test the hypothesis that Purkinje cell neurotransmission is essential for refining prefunctional developmental zones into sharp functional zones. Our results show that inhibitory synaptic transmission in Purkinje cells is necessary for the precise patterning of Purkinje cell zones and the topographic targeting of mossy fiber afferents. As expected, blocking Purkinje cell neurotransmission caused ataxia. Using in vivo electrophysiology, we demonstrate that loss of Purkinje cell communication altered the firing rate and pattern of their target cerebellar nuclear neurons. Analysis of Purkinje cell complex spike firing revealed that feedback in the cerebellar nuclei to inferior olive to Purkinje cell loop is obstructed. Loss of Purkinje neurotransmission also caused ectopic zonal expression of tyrosine hydroxylase, which is only expressed in adult Purkinje cells when calcium is dysregulated and if excitability is altered. Our results suggest that Purkinje cell inhibitory neurotransmission establishes the functional circuitry of the cerebellum by patterning the molecular zones, fine-tuning afferent circuitry, and shaping neuronal activity. PMID:24920627

  4. Speech and oral motor learning in individuals with cerebellar atrophy.

    PubMed

    Schulz, G M; Dingwall, W O; Ludlow, C L

    1999-10-01

    The purpose of this study was to determine whether cerebellar pathology interferes with motor learning for either speech or novel tasks. Practice effects were contrasted between persons with cerebellar cortical atrophy (CCA) and control participants on previously learned real speech, nonsense speech, and novel nonspeech oral-movement tasks. Studies of limb motor learning suggested that control participants would evidence reduced variability, increased speed of movement, and reduced movement amplitude with practice as compared with the CCA group. No significant differences were found between the real- and nonsense-speech tasks. For both speech tasks, although neither group reduced their movement variability with practice, both groups significantly reduced jaw closing displacement and velocity with practice. For the novel nonspeech oral-movement task, no change with practice was observed in either group in terms of variability, amplitude, or peak velocity. No effects of cerebellar pathology were seen in either the speech- or oral-movement tasks. These results demonstrated that with practice of speech tasks, a previously learned motor skill, movement speed and displacement decreased in both groups. Therefore, the effects of practice differed between previously learned speech tasks and the novel oral-movement task regardless of cerebellar pathology. PMID:10515513

  5. Primary cerebellar endodermal sinus tumor: A case report.

    PubMed

    Kuang, Hongmei; Zhang, Chun; Gong, Honghan; Guo, Linghong; Yu, Chen; Zeng, Xianjun

    2014-10-01

    Endodermal sinus tumors are rare malignant germ cell tumors that usually originate from the gonads and are rarely observed extragonadally. Pure primary endodermal sinus tumors of the cerebellar hemisphere are extremely rare and patients diagnosed with the disease often have a poor prognosis. The symptoms of YSTs are unspecific and associated with the location of tumors. Intracranial YSTs (such as cerebellar hemispheres) always present with symptoms including headache and poor vision. The present study reports the case of a three-year-old male who presented to The First Affiliated Hospital of Nanchang University (Nanchang, China) with a headache that had persisted for one month, and then worsened for the last 10 days. This was accompanied by vomiting and gait disturbance. An abnormal signal mass was identified in the left cerebellar hemisphere on brain magnetic resonance imaging. The case initially presented as a medulloblastoma and the patient was followed up for six months. The final pathology report revealed an endodermal sinus tumor, also known as a yolk sac tumor. Six months following resection of the left cerebellar tumor, the patient succumbed to recurrence of the disease, due to acute vomiting and severe headache. PMID:25202397

  6. Translational Approach to Behavioral Learning: Lessons from Cerebellar Plasticity

    PubMed Central

    Cheron, Guy; Dan, Bernard; Márquez-Ruiz, Javier

    2013-01-01

    The role of cerebellar plasticity has been increasingly recognized in learning. The privileged relationship between the cerebellum and the inferior olive offers an ideal circuit for attempting to integrate the numerous evidences of neuronal plasticity into a translational perspective. The high learning capacity of the Purkinje cells specifically controlled by the climbing fiber represents a major element within the feed-forward and feedback loops of the cerebellar cortex. Reciprocally connected with the basal ganglia and multimodal cerebral domains, this cerebellar network may realize fundamental functions in a wide range of behaviors. This review will outline the current understanding of three main experimental paradigms largely used for revealing cerebellar functions in behavioral learning: (1) the vestibuloocular reflex and smooth pursuit control, (2) the eyeblink conditioning, and (3) the sensory envelope plasticity. For each of these experimental conditions, we have critically revisited the chain of causalities linking together neural circuits, neural signals, and plasticity mechanisms, giving preference to behaving or alert animal physiology. Namely, recent experimental approaches mixing neural units and local field potentials recordings have demonstrated a spike timing dependent plasticity by which the cerebellum remains at a strategic crossroad for deciphering fundamental and translational mechanisms from cellular to network levels. PMID:24319600

  7. Is a Cerebellar Deficit the Underlying Cause of Reading Disabilities?

    ERIC Educational Resources Information Center

    Irannejad, Shahrzad; Savage, Robert

    2012-01-01

    This study investigated whether children with dyslexia differed in their performance on reading, phonological, rapid naming, motor, and cerebellar-related tasks and automaticity measures compared to reading age (RA)-matched and chronological age (CA)-matched control groups. Participants were 51 children attending mainstream English elementary…

  8. Grip-load force coordination in cerebellar patients.

    PubMed

    Serrien, D J; Wiesendanger, M

    1999-09-01

    The study examined the anticipatory grip force modulations to load force changes during a drawer-opening task. An impact force was induced by a mechanical stop which abruptly arrested movement of the pulling hand. In performing this task, normal subjects generated a typical grip force profile characterized by an initial force impulse related to drawer movement onset, followed by a ramp-like grip force increase prior to the impending load perturbation. Finally, a reactive response was triggered by the impact. In patients with bilateral cerebellar dysfunction, the drawer-opening task was performed with an alternative control strategy. During pulling, grip force was increased to a high (overestimated) default level. The latter suggests that cerebellar patients were unable to adjust and to scale precisely the grip force according to the load force. In addition, the latency between impact and reactive activity was prolonged in the patients, suggesting an impaired cerebellar transmission of the long-latency responses. In conclusion, these data demonstrate the involvement of cerebellar circuits in both proactive and reactive mechanisms in view of predictable load perturbations during manipulative behavior. PMID:10473743

  9. Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Paslawski, Teresa; Duffy, Joseph R.; Vernino, Steven

    2005-01-01

    Paraneoplastic cerebellar degeneration (PCD) is an autoimmune disease that can be associated with cancer of the breast, lung, and ovary. The clinical presentation of PCD commonly includes ataxia, visual disturbances, and dysarthria. The speech disturbances associated with PCD have not been well characterized, despite general acceptance that…

  10. Hippocampo-cerebellar theta band phase synchrony in rabbits.

    PubMed

    Wikgren, J; Nokia, M S; Penttonen, M

    2010-02-17

    Hippocampal functioning, in the form of theta band oscillation, has been shown to modulate and predict cerebellar learning of which rabbit eyeblink conditioning is perhaps the most well-known example. The contribution of hippocampal neural activity to cerebellar learning is only possible if there is a functional connection between the two structures. Here, in the context of trace eyeblink conditioning, we show (1) that, in addition to the hippocampus, prominent theta oscillation also occurs in the cerebellum, and (2) that cerebellar theta oscillation is synchronized with that in the hippocampus. Further, the degree of phase synchrony (PS) increased both as a response to the conditioning stimuli and as a function of the relative power of hippocampal theta oscillation. However, the degree of PS did not change as a function of either training or learning nor did it predict learning rate as the hippocampal theta ratio did. Nevertheless, theta band synchronization might reflect the formation of transient neural assemblies between the hippocampus and the cerebellum. These findings help us understand how hippocampal function can affect eyeblink conditioning, during which the critical plasticity occurs in the cerebellum. Future studies should examine cerebellar unit activity in relation to hippocampal theta oscillations in order to discover the detailed mechanisms of theta-paced neural activity. PMID:19945512

  11. Caytaxin Deficiency Disrupts Signaling Pathways in Cerebellar Cortex

    PubMed Central

    Xiao, Jianfeng; Gong, Suzhen; LeDoux, Mark S.

    2007-01-01

    The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as a site of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time RT-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and calcium-transporting plasma membrane ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex. PMID:17092653

  12. The history of the development of the cerebellar examination.

    PubMed

    Fine, Edward J; Ionita, Catalina C; Lohr, Linda

    2002-12-01

    The cerebellar examination evolved from observations of experimental lesions made by neurophysiologists and clinical descriptions of patients with trauma to the cerebellum. At the beginning of the 19th century, neurophysiologists such as Luigi Rolando, Marie-Jean-Pierre Flourens, and John Call Dalton, Jr. ablated portions of the cerebellum of a variety of animals and observed staggering gait, clumsiness, and falling from side to side without loss of strength. They concluded that the cerebellum coordinated voluntary movements. In 1899, Joseph Francois Félix Babinski observed that patients with cerebellar lesions could not execute complex movements without breaking down into their elemental movements and described the defect as dysmetria. In 1902, Babinski coined the term dysdiodochokinesis to describe the inability to perform rapid execution of movements requiring alternate contractions of agonist and antagonist muscles. Gordon Holmes in 1904 described the phenomena of rebound, noting that if a limb ipsilateral to a cerebellar lesion is suddenly released from tension, the appendage will flail. In 1917, Gordon Holmes reported hypotonia and dysmetria in men wounded by gunshot wounds to their cerebellum. These observations were rapidly included in descriptions of the cerebellar examination in popular contemporaneous textbooks of neurology. Modern observations have demonstrated that the cerebellum influences such cognitive functions such as planning, verbal fluency, abstract reasoning, prosody, and use of correct grammar. PMID:12539058

  13. Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.

    PubMed

    Iwama, Kazuhiro; Sasaki, Masayuki; Hirabayashi, Shinichi; Ohba, Chihiro; Iwabuchi, Emi; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Ito, Shuichi; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-06-01

    Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy. PMID:26888482

  14. Interhemispheric Asymmetry of Corticomotor Excitability After Chronic Cerebellar Infarcts

    PubMed Central

    Cohen, Leonardo G.; da Cunha Pinho, Marco; Yamamoto, Fábio Iuji; Marchiori, Paulo Eurípedes; Scaff, Milberto; Conforto, Adriana Bastos

    2016-01-01

    Early after stroke, there is loss of intracortical facilitation (ICF) and increase in short-interval intracortical inhibition (SICI) in the primary motor cortex (M1) contralateral to a cerebellar infarct. Our goal was to investigate intracortical M1 function in the chronic stage following cerebellar infarcts (>4 months). We measured resting motor threshold (rMT), SICI, ICF, and ratios between motor-evoked potential amplitudes (MEP) and supramaximal M response amplitudes (MEP/M; %), after transcranial magnetic stimulation was applied to the M1 contralateral (M1contralesional) and ipsilateral (M1ipsilesional) to the cerebellar infarct in patients and to both M1s of healthy age-matched volunteers. SICI was decreased in M1contralesional compared to M1ipsilesional in the patient group in the absence of side-to-side differences in controls. There were no significant interhemispheric or between-group differences in rMT, ICF, or MEP/M (%). Our results document disinhibition of M1contralesional in the chronic phase after cerebellar stroke. PMID:20461489

  15. Cerebellar glucose consumption in normal and pathologic states using fluorine-FDG and PET

    SciTech Connect

    Kushner, M.; Tobin, M.; Alavi, A.; Chawluk, J.; Rosen, M.; Fazekas, F.; Alavi, J.; Reivich, M.

    1987-11-01

    We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ((/sup 18/F)FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus, analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.

  16. Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01–08)

    PubMed Central

    Wen, Patrick Y.; Yung, W.K. Alfred; Lamborn, Kathleen R.; Norden, Andrew D.; Cloughesy, Timothy F.; Abrey, Lauren E.; Fine, Howard A.; Chang, Susan M.; Robins, H. Ian; Fink, Karen; DeAngelis, Lisa M.; Mehta, Minesh; Di Tomaso, Emmanuelle; Drappatz, Jan; Kesari, Santosh; Ligon, Keith L.; Aldape, Ken; Jain, Rakesh K.; Stiles, Charles D.; Egorin, Merrill J.; Prados, Michael D.

    2009-01-01

    Platelet-derived growth factor (PDGF) and its receptors (PDGFR) are frequently coexpressed in meningiomas, potentially contributing to their pathogenesis. The North American Brain Tumor Consortium conducted a phase II study to evaluate the therapeutic potential of imatinib mesylate (Gleevec), a PDGFR inhibitor, in patients with recurrent meningiomas. Patients were stratified into benign (WHO grade I) meningiomas or atypical (WHO grade II) and malignant (WHO grade III) meningiomas. The primary end point was 6-month progression-free survival (6M-PFS). Patients requiring enzyme-inducing antiepileptic drugs were ineligible. Patients received imatinib at a dose of 600 mg/day for the first 4-week cycle and then gradually increased to 800 mg/day for subsequent cycles, if there were no unacceptable toxicities. Plasma concentrations of imatinib and its active metabolite, CGP74588, were assessed. Twenty-three heavily pre-treated patients were enrolled into the study (13 benign, 5 atypical, and 5 malignant meningiomas), of whom 22 were eligible. The study was closed prematurely due to slow accrual. Tissue was available only from a minority of patients, but in these specimens there was uniform distribution of PDGFR, the drug target. Imatinib was generally well tolerated. Of 19 patients evaluable for response, 10 progressed at the first scan, and 9 were stable. There were no complete or partial responses. Overall median PFS was 2 months (range, 0.7–34 months); 6M-PFS was 29.4%. For benign meningiomas, median PFS was 3 months (range, 1.1–34 months); 6M-PFS was 45%. For atypical and malignant meningiomas, median PFS was 2 months (range, 0.7–3.7 months); 6M-PFS was 0%. Cycle 1 trough concentrations of imatinib and CGP74588 were 2,129 ± 1,600 ng/ml and 517 ± 326 ng/ml, respectively. Single-agent imatinib was well tolerated but had no significant activity in recurrent meningiomas. Trough plasma concentrations of imatinib exceeded those associated with imatinib activity in

  17. Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01-08).

    PubMed

    Wen, Patrick Y; Yung, W K Alfred; Lamborn, Kathleen R; Norden, Andrew D; Cloughesy, Timothy F; Abrey, Lauren E; Fine, Howard A; Chang, Susan M; Robins, H Ian; Fink, Karen; Deangelis, Lisa M; Mehta, Minesh; Di Tomaso, Emmanuelle; Drappatz, Jan; Kesari, Santosh; Ligon, Keith L; Aldape, Ken; Jain, Rakesh K; Stiles, Charles D; Egorin, Merrill J; Prados, Michael D

    2009-12-01

    Platelet-derived growth factor (PDGF) and its receptors (PDGFR) are frequently coexpressed in meningiomas, potentially contributing to their pathogenesis. The North American Brain Tumor Consortium conducted a phase II study to evaluate the therapeutic potential of imatinib mesylate (Gleevec), a PDGFR inhibitor, in patients with recurrent meningiomas. Patients were stratified into benign (WHO grade I) meningiomas or atypical (WHO grade II) and malignant (WHO grade III) meningiomas. The primary end point was 6-month progression-free survival (6M-PFS). Patients requiring enzyme-inducing antiepileptic drugs were ineligible. Patients received imatinib at a dose of 600 mg/day for the first 4-week cycle and then gradually increased to 800 mg/day for subsequent cycles, if there were no unacceptable toxicities. Plasma concentrations of imatinib and its active metabolite, CGP74588, were assessed. Twenty-three heavily pretreated patients were enrolled into the study (13 benign, 5 atypical, and 5 malignant meningiomas), of whom 22 were eligible. The study was closed prematurely due to slow accrual. Tissue was available only from a minority of patients, but in these specimens there was uniform distribution of PDGFR, the drug target. Imatinib was generally well tolerated. Of 19 patients evaluable for response, 10 progressed at the first scan, and 9 were stable. There were no complete or partial responses. Overall median PFS was 2 months (range, 0.7-34 months); 6M-PFS was 29.4%. For benign meningiomas, median PFS was 3 months (range, 1.1-34 months); 6M-PFS was 45%. For atypical and malignant meningiomas, median PFS was 2 months (range, 0.7-3.7 months); 6M-PFS was 0%. Cycle 1 trough concentrations of imatinib and CGP74588 were 2,129 +/- 1,600 ng/ml and 517 +/- 326 ng/ml, respectively. Single-agent imatinib was well tolerated but had no significant activity in recurrent meningiomas. Trough plasma concentrations of imatinib exceeded those associated with imatinib activity in chronic

  18. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas.

    PubMed

    Boström, J; Meyer-Puttlitz, B; Wolter, M; Blaschke, B; Weber, R G; Lichter, P; Ichimura, K; Collins, V P; Reifenberger, G

    2001-08-01

    We investigated 67 meningothelial tumors (20 benign meningiomas, 34 atypical meningiomas, and 13 anaplastic meningiomas) for losses of genetic information from chromosome arms 1p and 9p, as well as for deletion, mutation, and expression of the tumor suppressor genes CDKN2A (p16(INKa)/MTS1), p14(ARF), CDKN2B (p15(INK4b)/MTS2) (all located at 9p21) and CDKN2C (1p32). Comparative genomic hybridization and microsatellite analysis showed losses on 1p in 11 anaplastic meningiomas (85%), 23 atypical meningiomas (68%), and 5 benign meningiomas (25%). One atypical meningioma with loss of heterozygosity on 1p carried a somatic CDKN2C mutation (c.202C>T: R68X). Losses on 9p were found in five anaplastic meningiomas (38%), six atypical meningiomas (18%), and one benign meningioma (5%). Six anaplastic meningiomas (46%) and one atypical meningioma (3%) showed homozygous deletions of the CDKN2A, p14(ARF), and CDKN2B genes. Two anaplastic meningiomas carried somatic point mutations in CDKN2A (c.262G>T: E88X and c.262G>A: E88K) and p14(ARF) (c.305G>T: G102V and c.305G>A: G102E). One anaplastic meningioma, three atypical meningiomas, and one benign meningioma without a demonstrated homozygous deletion or mutation of CDKN2A, p14(ARF), or CDKN2B lacked detectable transcripts from at least one of these genes. Hypermethylation of CDKN2A, p14(ARF), and CDKN2B could be demonstrated in one of these cases. Taken together, our results indicate that CDKN2C is rarely altered in meningiomas. However, the majority of anaplastic meningiomas either show homozygous deletions of CDKN2A, p14(ARF), and CDKN2B, mutations in CDKN2A and p14(ARF), or lack of expression of one or more of these genes. Thus, inactivation of the G(1)/S-phase cell-cycle checkpoint is an important aberration in anaplastic meningiomas. PMID:11485924

  19. Gaze holding deficits discriminate early from late onset cerebellar degeneration.

    PubMed

    Tarnutzer, Alexander A; Weber, K P; Schuknecht, B; Straumann, D; Marti, S; Bertolini, G

    2015-08-01

    The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined

  20. Relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma

    PubMed Central

    Peng, Yihua; Shao, Chunhong; Gong, Ye; Wu, Xuehai; Tang, Weijun; Shi, Shenxun

    2015-01-01

    Background The purpose of this study is to assess the relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma. Methods We enrolled 65 consecutive patients with meningioma and 31 normal controls matched for age, gender, and education. The patients were divided into frontal or non-frontal (NF) meningioma groups based on magnetic resonance imaging; the frontal group was then subdivided to dorsolateral frontal (DLF), medial frontal (MF), and ventral frontal (VF) groups. Tumor size and brain edema were also recorded. Apathy was assessed by the Apathy Evaluation Scale (AES). Assessments were carried out 1 week before and 3 months after surgery, respectively. Logistic regression analysis was performed to identify the predictive effect of tumor size, location, and brain edema on apathy. Analysis of variance and chi-square analysis were applied to compare apathy scores and apathy rates among the frontal, NF, and normal control groups, and all subgroups within the frontal group. Results Compared with the NF and control groups, the mean AES score was much higher in the frontal group (34.0±8.3 versus 28.63±6.0, P=0.008, and 26.8±4.2, P<0.001). Subgroup analysis showed that AES scores in the MF group (42.1±6.6) and VF group (34.7±8.0) were higher than in the DLF group (28.5±4.36), NF group, and control group (P<0.05). The apathy rate was 63.6% in the MF group and 25% in the VF group, and significantly higher than in the DLF (5.6%), NF (5.3%), and control (0%) groups (P<0.001). A moderate correlation was found between AES score and mean diameter of the meningioma in all patient groups. Further analysis demonstrated that the correlation existed in the DLF (r=0.52, P=0.032), MF (r=0.84, P<0.001), and VF (r=0.64, P=0.008) groups, but not in the NF group (r=0.19, P=0.448). The AES score was much higher in patients with brain edema than in those without brain edema (34.73±8.28 versus 28.77±4.20, t=3.545, P=0.001). In