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ABSTRACT: INTRODUCTION: Reversible posterior leukoencephalopathy syndrome -- a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures -- is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. CASE PRESENTATION: A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established.Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. CONCLUSION: This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.
Journal of Medical Case Reports 01/2013; 7(1):14.
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Clinical neurology and neurosurgery 07/2012; · 1.30 Impact Factor
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ABSTRACT: Ependymomas are primary tumors of the central nervous system that typically originate from the walls of the cerebral ventricles
or from the spinal canal. The pathogenesis of these tumors is poorly understood, and prognostic assessment based on histologic
features and clinical parameters is difficult. The aim of this study was to investigate the molecular heterogeneity of ependymomas.
We used cDNA microarrays and RT-PCR to examine gene expression in 47 ependymomas. We present results for five comparisons:
(1) tumors from children and adults with poor versus favorable outcome, (2) tumors from children with poor versus favorable
outcome, (3) tumors with high versus low proliferation indices, (4) subependymomas versus myxopapillary ependymomas, and (5)
spinal versus intracranial ependymomas. For patients with an overall survival >10years after diagnosis, we identified 27
genes associated with favorable prognosis. In contrast, overexpression of BNIP3, MRC1, EPHB3, GLIS3, CDK4, COL4A2, EBP, NRCAM,
and CCNA1 genes in tumors with high proliferation indices was associated with a poor outcome. Thirty genes, including ETV6,
YWHAE, TOP2A, TLR2, IRAK1, TIA1, and UFD1L were found to be highly expressed in subependymomas but not myxopapillary ependymomas.
Also, 30 genes were differentially expressed in spinal versus intracranial ependymomas. There was no relationship between
expression profiles and tumor grade, patient age, and patient gender. Our results provide insight into specific molecular
events underlying ependymoma tumorigenesis and may contribute to more accurate diagnosis and prediction of clinical outcome.
Acta Neuropathologica 04/2012; 113(3):325-337. · 9.32 Impact Factor
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ABSTRACT: Objectives. Although Alzheimer's disease (AD) is the most common form of dementia in the elderly, its aetiology remains mostly unknown. A potential pathophysiological mechanism for AD arises from the knowledge that insulin is also synthesized independently in the central nervous system and is involved in the regulation of memory formation. AD may represent a brain-specific form of insulin resistance. Methods. We used immunohistochemistry to investigate the numbers of cells expressing insulin receptor β-subunit (IRβ) and phosphorylated PPARγ (PPARγ(p)) in human post-mortem tissue from patients with AD; AD combined with type 2 diabetes mellitus (T2DM); just T2DM , and from aged-matched controls. These numbers were evaluated in frontal cortex and in dorsal/ventral parts of the hippocampus. Results. We observed significantly lower numbers of IRβ positive cells in AD cases compared to all other groups in all investigated brain regions. Also significantly more PPARγ(p) positive cells occurred in each patient group compared to control. Conclusions. T2DM and AD may not be directly linked, but may share common histological features including lower numbers of IRβ positive cells and higher numbers of PPARγ(p) positive cells in all investigated brain regions. These observations may at least partially explain the increased frequency of AD in elderly diabetic patients.
The World Journal of Biological Psychiatry 02/2012; · 2.38 Impact Factor
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ABSTRACT: The aetiology of Parkinson's disease (PD) is yet to be fully understood but it is becoming more and more evident that neuronal cell death may be multifactorial in essence. The main focus of PD research is to better understand substantia nigra homeostasis disruption, particularly in relation to the wide-spread deposition of the aberrant protein α-synuclein. Microarray technology contributed towards PD research with several studies to date and one gene, ALDH1A1 (Aldehyde dehydrogenase 1 family, member A1), consistently reappeared across studies including the present study, highlighting dopamine (DA) metabolism dysfunction resulting in oxidative stress and most probably leading to neuronal cell death. Neuronal cell death leads to increased inflammation through the activation of astrocytes and microglia. Using our dataset, we aimed to isolate some of these pathways so to offer potential novel neuroprotective therapeutic avenues. To that effect our study has focused on the upregulation of P2X7 (purinergic receptor P2X, ligand-gated ion channel, 7) receptor pathway (microglial activation) and on the NOS3 (nitric oxide synthase 3) pathway (angiogenesis). In summary, although the exact initiator of striatal DA neuronal cell death remains to be determined, based on our analysis, this event does not remain without consequence. Extracellular ATP and reactive astrocytes appear to be responsible for the activation of microglia which in turn release proinflammatory cytokines contributing further to the parkinsonian condition. In addition to tackling oxidative stress pathways we also suggest to reduce microglial and endothelial activation to support neuronal outgrowth.
Parkinson's disease. 01/2012; 2012:214714.
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Camelia Maria Monoranu,
Edna Grünblatt,
Jasmin Bartl,
Andrea Meyer,
Manuela Apfelbacher,
Daniela Keller,
Tanja M Michel,
Safa Al-Saraj,
Andrea Schmitt,
Peter Falkai,
Wolfgang Roggendorf,
Jürgen Deckert,
Isidro Ferrer,
Peter Riederer
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ABSTRACT: Postmortem brain tissue has been reported to be suitable to delineate regional pattern of possible disturbances underlying epigenetic functionality. However, from many parameters that have been detected in postmortem brain regions it is noteworthy that an effect of postmortem interval (PMI), storage time and premortem parameters should not be underestimated. Our previous investigation revealed that tryptophan (TRP) levels in postmortem brain tissue is affected by PMI and storage time. Since, alteration in TRP levels are assumed to be due to protein degradation, we further investigated whether TRP correlates to variables such as RNA, proteins and DNA modulators. In addition, we aimed to elucidate whether established postmortem variables may influence epigenetic parameters. These were investigated in well characterized postmortem human brain tissue originating from the European Brain Bank consortium II (BNEII). We could confirm previous findings, in which some protein levels alter because of prolonged PMI. Similarly, we demonstrated an influence of increased storage period on TRP levels, which might indicate degradation of proteins. Still not all proteins degrade in a similar manner, therefore a specific analysis for the protein of interest would be recommended. We found that methyltransferase- and acetyltransferase-activities were relatively preserved with PMI and storage duration. In conclusion, preservation of acetyltransferase- and methyltransferase-activities provides possible evidence of stability for epigenetic studies using postmortem tissue.
Cell and Tissue Banking 11/2011; 12(4):289-97. · 0.96 Impact Factor
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ABSTRACT: Brain bank centers around the world attempt to standardize postmortem brain collection and quality control. Antemortem as well postmortem factors may influence tissue quality. Previously, we could demonstrate that increased tryptophan (TRP) levels significantly correlate to prolonged postmortem interval (PMI) and storage duration, whereas pH-value altered merely as consequence of prolonged agonal state and ischemic brain damage additionally to repeated freeze and thaw cycles. Therefore, we aimed to investigate in artificial PMI conditions, with three brain tissue storage temperatures (4°C, room temperature and 37°C) as well as oxidizing conditions (open/close tube), whether TRP levels and pH-value alter. We could confirm that prolonged PMI at higher storage temperatures and oxidizing conditions significantly correlate to increased TRP levels, while pH-value did not correlate at all. In conclusion, from these results PMI intervals until autopsy should be kept as short as possible and storage until autopsy should be at 4°C in order to preserve brain tissue quality as much as possible.
Neurochemistry International 12/2010; 57(7):819-22. · 2.86 Impact Factor
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ABSTRACT: To illustrate magnetic resonance neurography findings of severe sciatic injury and muscle denervation related to deep gluteal endometriosis at the sciatic notch.
Case report.
Academic teaching hospital.
A 39-year-old woman with a 4-year history of sciatica related to the menstrual cycle.
Surgical exploration of the sciatic notch for diagnostic confirmation, external neurolysis of the sciatic nerve, and eventual pharmacologic treatment.
Magnetic resonance neurography imaging revealed severe neuropathic injury and muscle denervation related to a deep infiltrative endometriotic focus at the sciatic notch, which was confirmed histologically on surgical exploration. Detailed electrodiagnostic and clinical neurologic examinations at initial presentation and during follow-up were obtained for further assessment of nerve degeneration, muscle denervation, and clinical recovery.
Initial gynecologic and eventual laparoscopic evaluation on persisting complaints were without pathological findings. When a progressive weakness of the leg was noted, magnetic resonance neurography revealed a severe axonal damage to the sciatic nerve and denervation of distal target muscles related to a diffuse infiltrative lesion at the sciatic notch. On surgical exploration, extragenital endometriosis was confirmed histologically. Considerable improvement in pain and strength occurred after pharmacologic therapy with a GnRH analogue.
This is the first report to describe imaging findings of magnetic resonance neurography in severe neuropathic injury of the sciatic nerve and subsequent muscle denervation related to a deep infiltrative gluteal endometriotic focus.
Fertility and sterility 02/2010; 94(1):351.e11-4. · 3.97 Impact Factor
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Edna Grünblatt, Camelia Maria Monoranu,
Manuela Apfelbacher,
Daniela Keller,
Tanja M Michel,
Irina Alafuzoff,
Isidro Ferrer,
Safa Al-Saraj,
Kathy Keyvani,
Andrea Schmitt,
Peter Falkai,
Jens Schittenhelm,
Catriona McLean,
Glenda M Halliday,
Clive Harper,
Jürgen Deckert,
Wolfgang Roggendorf,
Peter Riederer
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ABSTRACT: Postmortem human brain tissue is widely used in neuroscience research, but use of tissue originating from different brain bank centers is considered inaccurate because of possible heterogeneity in sample quality. There is thus a need for well-characterized markers to assess the quality of postmortem brain tissue. Toward this aim, we determined tryptophan (TRP) concentrations, phosphofructokinase-1 and glutamate decarboxylase activities in 119 brain tissue samples. These neurochemical parameters were tested in samples from autopsied individuals, including control and pathological cases provided by 10 different brain bank centers. Parameters were assessed for correlation with agonal state, postmortem interval, age and gender, brain region, preservation and freezing methods, storage conditions and storage time, RNA integrity, and tissue pH value. TRP concentrations were elevated significantly (p = 0.045) with increased postmortem interval; which might indicate increased protein degradation. Therefore, TRP concentration might be one useful and convenient marker for estimating the quality of human postmortem brain tissue.
Journal of Neurochemistry 07/2009; 110(5):1400-8. · 4.06 Impact Factor
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ABSTRACT: Numerous human malignancies, including brain tumors, have been reported to show aberrations on chromosome 9. In our previous screening study in ependymomas, we used microsatellite analysis to identify frequent aberrations on this chromosome. To refine our preliminary analysis of candidate regions, here we use 15 polymorphic microsatellite markers spanning the entire chromosome 9. A total of 48 pairs of matched normal and tumor specimens from patients with ependymoma, including 28 children (mean age, 4.4 years) and 20 adults (mean age, 44.9 years), were genotyped. Allelic imbalances were found in 30/48 patients (62.5%). Pediatric tumors, which were predominantly anaplastic, showed fewer aberrations (57.1%) than adult tumors (70%), and two common regions of deletions were identified (9p21.1 approximately p22.3 and 9q31.3 approximately q33.2). We found that 9q31.3 approximately q33.2, an approximately 8.5-megabase segment containing the DCR1 gene, exhibited the highest number of aberrations (n=33). Adults with ependymomas harboring aberrations on chromosome 9 (n=14) showed significantly longer overall survival than patients of the same group without this aberration (n=6; P=0.034), irrespective of the extent of resection in multivariate analysis. Aberrations of chromosome 9, and particularly of DCR1, may play a role in the prognostic evaluation for ependymomas in adults in the future. In pediatric patients, genetic aberrations were found significantly more often in supratentorial tumors than in tumors with infratentorial location (P=0.007). This result may underscore differences in the origin of these tumors.
Cancer genetics and cytogenetics 07/2009; 191(2):90-6. · 1.54 Impact Factor
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Camelia-Maria Monoranu,
Manuela Apfelbacher,
Edna Grünblatt,
Bernhard Puppe,
Irina Alafuzoff,
Isidro Ferrer,
Safa Al-Saraj,
Kathy Keyvani,
Andrea Schmitt,
Peter Falkai,
Jens Schittenhelm,
Glenda Halliday,
Jillian Kril,
Clive Harper,
Catriona McLean,
Peter Riederer,
Wolfgang Roggendorf
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ABSTRACT: Abstract Aims: Most brain diseases are complex entities. Although animal models or cell culture experiments mimic some disease aspects, human postmortem brain tissue remains essential to advance our understanding of brain diseases using biochemical and molecular techniques. Postmortem artifacts must be properly understood, standardized, and either eliminated or factored into such experiments. Here we examine the influence of several pre- and postmortem factors on pH, and discuss the role of pH as a biochemical marker for brain tissue quality. Methods: We assessed brain tissue pH in 339 samples from 116 brains provided by 8 different European and 2 Australian brain bank centres. We correlated brain pH with tissue source, postmortem delay, age, gender, freezing method, storage duration, agonal state, or and brain ischaemia. Results: Our results revealed that only prolonged agonal state and ischaemic brain damage influenced brain tissue pH next to repeated freeze/thaw cycles. Conclusions: pH measurement in brain tissue is a good indicator of premortem events in brain tissue and it signals limitations for postmortem investigations.
Neuropathology and Applied Neurobiology 01/2009; · 3.80 Impact Factor
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Martin Hasselblatt,
Jaroslaw Jozwiak,
Karin Mayer, Camelia-Maria Monoranu,
Tilmann Schweitzer,
Nicolas U Gerber,
Jürgen Krauss,
Christian Schropp,
Stefan Bleier,
Katarzyna Kotulska,
Stefan Rutkowski,
Torsten Pietsch,
Niels Sörensen,
Christian Kersting,
Wolfgang Roggendorf,
Werner Paulus
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ABSTRACT: We here report an unusual tumor of the suprasellar region featuring a papillary growth pattern and cytokeratin expression in a 10-year-old boy with tuberous sclerosis. This hitherto undescribed low-grade hypothalamic tumor extends the spectrum of tumors associated with the tuberous sclerosis complex.
The American journal of surgical pathology 09/2008; 32(10):1578-80. · 4.06 Impact Factor
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ABSTRACT: Transketolases link the Embden-Meyerhof pathway to the pentose phosphate pathway. An influence of p-Akt on this metabolism was described. This study was performed to compare the expression of transketolase-like 1 (TKTL1) and p-Akt in glioblastoma multiforme (GBM) and other astrocytic gliomas (AGs, grades II and III). We analyzed 15 GBMs, 15 AGs (grade II), and 3 normal brain samples for TKTL1 expression by semiquantitative reverse transcription-polymerase chain reaction and Western blotting and 23 GBMs, 9 grade III AGs, and 7 grade II AGs immunohistochemically (TKTL1 and p-Akt). On the protein level, TKTL1 was significantly overexpressed in tumors. Immunohistochemically, the tumor grade significantly correlated with expression of TKTL1. Compared with grades II and III AGs, GBMs showed higher expression of TKTL1, more positive tumors, and a higher percentage of positive tumor cells. The percentage of positive cells for TKTL1 and p-Akt was significantly correlated. These observations could lead to additional therapeutic options targeting a specific blockade of TKTL1 enzyme activity.
American Journal of Clinical Pathology 08/2008; 130(1):50-7. · 2.60 Impact Factor
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ABSTRACT: Losses and rearrangements of genetic material on chromosome 6q are frequently found in several human malignancies, including primary central nervous system tumors. We previously used microsatellite analysis of ependymomas to identify frequent deletions in regions 6q15 approximately q16, 6q21 approximately q22.1, and 6q24.3 approximately q25.3. To refine our preliminary analysis of potential prognostic regions, we used a panel of 25 microsatellite markers located between 6q15 and 6qter in 49 pairs of matched normal and tumor specimens from 28 children and 21 adults with ependymoma. Allelic deletions were detected in 34 of 49 patients (69%), and two common regions of deletions (6q24.3 and 6q25.2 approximately q25.3) were identified. A short segment of approximately 0.4 Mb between D6S1612 and D6S363 on 6q25.3, containing the SNX9 and SYNJ2 genes, exhibited the highest number of aberrations (n = 38). Pediatric tumors showed slightly fewer aberrations (64%) than adult tumors (76%) and also predominantly exhibited small interstitial deletions, in contrast to the extensive losses of genetic material in adults. Pediatric anaplastic intracranial (supra- and infratentorial) ependymomas harboring the 6q25.3 deletion (n = 9) showed significantly longer overall survival than did patients of the same group without the aberration (n = 6), independent of the extent of resection (P = 0.013). This supports the identified deletion on 6q25.3 as a candidate favorable prognostic parameter and warrants further investigation.
Cancer Genetics and Cytogenetics 05/2008; 182(1):18-26. · 1.39 Impact Factor
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ABSTRACT: Sporadic Alzheimer's (AD) and Parkinson's disease (PD) are late-onset neurodegenerative diseases with tremendous impact on lives of affected individuals. There is a great probability of developing concurrent Parkinsonism in AD and vice-versa than would be predicted by independent prevalence of each disease. We hypothesize that in sporadic AD as well as PD a combination of environmental effects and gene expression may affect specific brain areas leading to neurodegeneration. We profiled gene expression of AD compared to PD and age matched controls post-mortem in the hippocampus, the gyrus-frontalis-medius (Gfm) and the cerebellum using Gene-Chip microarray (Affymetrix) and quantitative-real-time-RT-PCR. Twelve genes altered in similar manner in AD and PD, while four genes showed differential expression profiles between AD and PD in different brain regions (cannabinoid-receptor-2, Histone-cluster-1-H3e, nicotinic-cholinergic-receptor-alpha6 and beta-site-APP-cleaving enzyme-1). Knowledge of selective gene expression profile can lead to better understanding of disease pathology and development of specific diagnosis and effective therapy.
Journal of Alzheimer's disease: JAD 01/2008; 12(4):291-311. · 3.74 Impact Factor
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ABSTRACT: Ependymomas are primary tumors of the central nervous system that typically originate from the walls of the cerebral ventricles or from the spinal canal. The pathogenesis of these tumors is poorly understood, and prognostic assessment based on histologic features and clinical parameters is difficult. The aim of this study was to investigate the molecular heterogeneity of ependymomas. We used cDNA microarrays and RT-PCR to examine gene expression in 47 ependymomas. We present results for five comparisons: (1) tumors from children and adults with poor versus favorable outcome, (2) tumors from children with poor versus favorable outcome, (3) tumors with high versus low proliferation indices, (4) subependymomas versus myxopapillary ependymomas, and (5) spinal versus intracranial ependymomas. For patients with an overall survival >10 years after diagnosis, we identified 27 genes associated with favorable prognosis. In contrast, overexpression of BNIP3, MRC1, EPHB3, GLIS3, CDK4, COL4A2, EBP, NRCAM, and CCNA1 genes in tumors with high proliferation indices was associated with a poor outcome. Thirty genes, including ETV6, YWHAE, TOP2A, TLR2, IRAK1, TIA1, and UFD1L were found to be highly expressed in subependymomas but not myxopapillary ependymomas. Also, 30 genes were differentially expressed in spinal versus intracranial ependymomas. There was no relationship between expression profiles and tumor grade, patient age, and patient gender. Our results provide insight into specific molecular events underlying ependymoma tumorigenesis and may contribute to more accurate diagnosis and prediction of clinical outcome.
Acta Neuropathologica 03/2007; 113(3):325-37. · 9.32 Impact Factor
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ABSTRACT: Background:
Preoperative particle embolization of intracranial meningiomas is frequently used to reduce intraoperative blood loss and to facilitate surgery. In selected cases palliative embolization without subsequent surgery has been proposed as alternative treatment to cause subsequent tumor shrinkage.
Case Report:
The authors report on an 81-year-old female patient presenting with a large frontotemporal convexity meningioma. Clinical symptoms included hemihypesthesia and seizures. Embolization of the middle meningeal artery blood supply was performed without technical problems, and the patient revealed no clinical symptoms throughout and shortly after the procedure. However, 2 h later the patient was found comatose with fixed dilated pupils. Computed tomography demonstrated massive intratumoral, subarachnoid, and subdural hemorrhage. The patient died 1 day later.
Conclusion:
Delayed hemorrhage may occur after particle embolization of meningiomas. Therefore, patients should be kept under close clinical surveillance after this procedure.
Hintergrund:
Die properative Partikelembolisation von Meningeomen wird hufig angewendet, um den intraoperativen Blutverlust zu reduzieren und die Operation zu vereinfachen. In ausgewhlten Fllen wurde eine palliative Embolisation ohne nachfolgende Operation als alternative Behandlung vorgeschlagen, um eine Schrumpfung des Tumors zu bewirken.
Fallbericht:
Die Autoren berichten ber eine 81-jhrige Patientin mit einem groen frontotemporalen Konvexittsmeningeom. Klinisch bestanden eine Hemihypsthesie und Krampfanflle. Eine Embolisation der tumorversorgenden ste der A. meningea media wurde ohne technische Probleme durchgefhrt. Die Patientin wies whrend und nach der Behandlung keine klinischen Symptome auf. Sie wurde jedoch 2 h spter komats mit weiten, lichtstarren Pupillen aufgefunden. Im Computertomogramm zeigte sich ein massives intratumorales, subarachnoidales und subdurales Hmatom. Die Patientin verstarb 1 Tag spter.
Schlussfolgerung:
Sekundre Einblutungen knnen nach Partikelembolisationen auftreten. Deswegen sollten die Patienten nach der Prozedur klinisch engmaschig berwacht werden.
Clinical Neuroradiology 11/2004; 14(4):256-260. · 1.09 Impact Factor
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ABSTRACT: Preoperative embolization of meningiomas is frequently used to facilitate surgery and to reduce intraoperative blood loss. The purpose of this study was to evaluate the frequency of procedure-related neurologic complications during and after particle embolization of intracranial meningiomas.
Between 1996 and 2004, 185 consecutive patients underwent particle embolization of an intracranial meningioma. Devascularization was performed by means of superselective probing of the tumor-feeding vessels and ensuing free-flow embolization with spherical particles. All procedures were performed with systemic heparinization.
Six patients (3.2%) had ischemic events with neurologic deficit. Two had amaurosis, and four patients presented with hemiparesis. Hemorrhage occurred in six patients (3.2%). In five of these patients, rapid microsurgical tumor removal resulted in a favorable outcome without persistent neurologic deficit. In one patient, massive intratumoral, subarachnoid, and subdural hemorrhage was lethal.
Particle embolization of meningiomas is associated with a substantial risk of ischemic and hemorrhagic events. The individual risk-to-benefit ratio of embolization should be thoroughly considered.
American Journal of Neuroradiology 26(6):1413-9. · 2.93 Impact Factor
