Gliosarcoma with extensive extracranial metastatic spread and familial coincidence: A case report.

Gliosarcoma is a rare histopathological subtype of glioblastoma. Metastatic spreading is unusual. In this report, we illustrate a case of gliosarcoma with extensive extracranial metastases with confirmation of histological and molecular concordance between the primary tumor and a metastatic lesion of the lung. Only the autopsy revealed the extent of metastatic spread and the hematogenous pattern of metastatic dissemination. Moreover, the case bared a familial coincidence of malignant glial tumors as the patient's son was diagnosed with a high-grade glioma shortly after the patient's death. By molecular analysis (Sanger and next generation panel sequencing), we could confirm that both patient's tumors carried mutations in the TP53 gene. Interestingly, the detected mutations were located in different exons. Altogether, this case draws attention to the fact that sudden clinical aggravation could be caused by the rare phenomenon of metastatic spread and should therefore be always taken into consideration, even at an early disease stage. Furthermore, the presented case highlights the contemporary value of autoptic pathological examination.

Heterotopia in Individuals with 22q11.2 Deletion Syndrome.

BACKGROUND AND PURPOSE: MR imaging studies and neuropathologic findings in individuals with 22q11.2 deletion syndrome show anomalous early brain development. We aimed to retrospectively evaluate cerebral abnormalities, focusing on gray matter heterotopia, and to correlate these with subjects' neuropsychiatric impairments. MATERIALS AND METHODS: Three raters assessed gray matter heterotopia and other morphologic brain abnormalities on 3D T1WI and T2*WI in 75 individuals with 22q11.2 deletion syndrome (27 females, 15.5 [SD, 7.4] years of age) and 53 controls (24 females, 12.6 [SD, 4.7] years of age). We examined the association among the groups' most frequent morphologic findings, general cognitive performance, and comorbid neuropsychiatric conditions. RESULTS: Heterotopia in the white matter were the most frequent finding in individuals with 22q11.2 deletion syndrome (n = 29; controls, n = 0; between-group difference, P < .001), followed by cavum septi pellucidi and/or vergae (n = 20; controls, n = 0; P < .001), periventricular cysts (n = 10; controls, n = 0; P = .007), periventricular nodular heterotopia (n = 10; controls, n = 0; P = .007), and polymicrogyria (n = 3; controls, n = 0; P = .3). However, individuals with these morphologic brain abnormalities did not differ significantly from those without them in terms of general cognitive functioning and psychiatric comorbidities. CONCLUSIONS: Taken together, our findings, periventricular nodular heterotopia or heterotopia in the white matter (possibly related to interrupted Arc cells migration), persistent cavum septi pellucidi and/or vergae, and formation of periventricular cysts, give clues to the brain development disorder induced by the 22q11.2 deletion syndrome. There was no evidence that these morphologic findings were associated with differences in psychiatric or cognitive presentation of the 22q11.2 deletion syndrome.

Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas.

BACKGROUND AND PURPOSE: Preclinical evidence points toward a metabolic reprogramming in isocitrate dehydrogenase (IDH) mutated tumor cells with down-regulation of the expression of genes that encode for glycolytic metabolism. We noninvasively investigated lactate and Cr concentrations, as well as intracellular pH using 1H/phosphorus 31 (31P) MR spectroscopy in a cohort of patients with gliomas. MATERIALS AND METHODS: Thirty prospectively enrolled, mostly untreated patients with gliomas met the spectral quality criteria (World Health Organization II [n = 7], III [n = 16], IV [n = 7]; IDH-mutant [n = 23]; IDH wild-type [n = 7]; 1p/19q codeletion [n = 9]). MR imaging protocol included 3D 31P chemical shift imaging and 1H single-voxel spectroscopy (point-resolved spectroscopy sequence at TE = 30 ms and TE = 97 ms with optimized echo spacing for detection of 2-hydroxyglutarate) from the tumor area. Values for absolute metabolite concentrations were calculated (phantom replacement method). Intracellular pH was determined from 31P chemical shift imaging. RESULTS: At TE = 97 ms, lactate peaks can be fitted with little impact of lipid/macromolecule contamination. We found a significant difference in lactate concentrations, lactate/Cr ratios, and intracellular pH when comparing tumor voxels of patients with IDH-mutant with those of patients with IDH wild-type gliomas, with reduced lactate levels and near-normal intracellular pH in patients with IDH-mutant gliomas. We additionally found evidence for codependent effects of 1p/19q codeletion and IDH mutations with regard to lactate concentrations for World Health Organization tumor grades II and III, with lower lactate levels in patients exhibiting the codeletion. There was no statistical significance when comparing lactate concentrations between IDH-mutant World Health Organization II and III gliomas. CONCLUSIONS: We found indirect evidence for metabolic reprogramming in IDH-mutant tumors with significantly lower lactate concentrations compared with IDH wild-type tumors and a near-normal intracellular pH.

Volumetry of Mesiotemporal Structures Reflects Serostatus in Patients with Limbic Encephalitis.

BACKGROUND AND PURPOSE: Limbic encephalitis is an autoimmune disease. A variety of autoantibodies have been associated with different subtypes of limbic encephalitis, whereas its MR imaging signature is uniformly characterized by mesiotemporal abnormalities across subtypes. Here, we hypothesized that patients with limbic encephalitis would show subtype-specific mesiotemporal structural correlates, which could be classified by supervised machine learning on an individual level. MATERIALS AND METHODS: T1WI MPRAGE scans from 46 patients with antibodies against glutamic acid decarboxylase and 34 patients with antibodies against the voltage-gated potassium channel complex (including 10 patients with leucine-rich glioma-inactivated 1 autoantibodies) and 48 healthy controls were retrospectively ascertained. Parcellation of the amygdala, hippocampus, and hippocampal subfields was performed using FreeSurfer. Volumes were extracted and compared between groups using unpaired, 2-tailed t tests. The volumes of hippocampal subfields were analyzed using a multivariate linear model and a binary decision tree classifier. RESULTS: Temporomesial volume alterations were most pronounced in an early stage and in the affected hemispheric side of patients. Statistical analysis revealed antibody-specific hippocampal fingerprints with a higher volume of CA1 in patients with glutamic acid decarboxylase-associated limbic encephalitis (P = .02), compared with controls, whereas CA1 did not differ from that in controls in patients with voltage-gated potassium channel complex autoantibodies. The classifier could successfully distinguish between patients with autoantibodies against leucine-rich glioma-inactivated 1 and glutamic acid decarboxylase with a specificity of 87% and a sensitivity of 80%. CONCLUSIONS: Our results suggest stage-, side- and antibody-specific structural correlates of limbic encephalitis; thus, they create a perspective toward an MR imaging-based diagnosis.

Cerebrovascular Reactivity during Prolonged Breath-Hold in Experienced Freedivers.

BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity. This multiparametric study investigated CBF, the spatial coefficient of variation as a correlate of arterial transit time and brain metabolism, dynamics during prolonged apnea. MATERIALS AND METHODS: Fifteen male freedivers (age range, 20-64 years; cumulative previous prolonged breath-holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T pseudocontinuous arterial spin-labeling and 31P-/1H-MR spectroscopy before, during, and after a 5-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. Correlation of temporal and regional cerebrovascular reactivity to blood gases and cumulative previous breath-holds of >2 minutes and 30 seconds in a lifetime was assessed. RESULTS: The spatial coefficient of variation of CBF (by arterial spin-labeling) decreased during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%, P = .001). CBF differed between the anterior and the posterior circulation during all phases (eg, during late breath-hold: MCA, 57.3 ± 14.2 versus posterior cerebral artery, 42.7 ± 10.8 mL/100 g/min; P = .001). There was an association between breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, -24.0%), cerebral lactate and adenosine diphosphate remained within physiologic ranges despite early signs of oxidative stress [-6.4% phosphocreatine / (adenosine triphosphate + adenosine diphosphate); P = .02]. CONCLUSIONS: This study revealed that the cerebral energy metabolism of trained freedivers withstands severe hypoxic hypercarbia in prolonged breath-hold due to a complex cerebrovascular hemodynamic response.

Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype.

BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study. RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%-100.0% and 62.6%-95.3%). WNT-activated nuclear ß-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2-22.3 cm3 versus 35.1-47.6 cm3; P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04). CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

[Interventional radiology in the head and neck region]. / Interventionelle Radiologie im Kopf-Hals-Bereich.

In interventional neuroradiology, endovascular embolization represents an important and helpful tool in the treatment of multiple head and neck diseases. These interventional procedures may be performed with curative intent, to reduce the surgical risk within a multimodal treatment concept, or to improve or at least maintain a good quality of life within a palliative therapy concept. In addition to a good understanding of disease pathology, knowledge of vascular anatomy, including collateral vessels and dangerous extracranial-intracranial anastomoses, is essential for successful treatment, as is implementation of an established technique using appropriate material. Indications for endovascular embolization are i. otherwise unmanageable bleeding (caused by e. g., trauma, vascular malformation, or tumor), ii. reduction of perioperative bleeding by preoperative embolization in case of a hypervascularized tumor, iii. selective induction of tumor necrosis by palliative embolization to enhance local tumor control. Major complications such as stroke, loss of vision, and cranial nerve palsy are mostly due to a lack of preinterventional evaluation. Regarding neurological deficits, interventions within the supply region of the external carotid artery have a complication rate below 1%.

[Clinical magnetic resonance imaging : Frequent incidental cerebral findings]. / Klinische Magnetresonanztomographie : Häufige zerebrale Zufallsbefunde.

The increasing use of magnetic resonance imaging (MRI) in clinical diagnostics means that patients and physicians are confronted more often with incidental findings. In the literature there are fluctuating data on the incidence of such findings and guidelines concerning the further procedure exist in only very few cases, such as incidental aneurysms and pituitary adenomas. The diagnostic and therapeutic implications which can be derived from incidental findings depend on multiple factors, such as anatomical location, patient age, comorbidity and patient wishes. For this reason it often makes sense to refer patients with incidental findings to an interdisciplinary neurological center at an early stage. In this review frequent incidental cerebral findings, epidemiological data, imaging criteria and, where possible, recommendations for the further procedure are shown.

[Magnetic resonance spectroscopy of brain tumors]. / MR-Spektroskopie bei Hirntumoren.

BACKGROUND: Conventional magnetic resonance imaging (MRI) under consideration of clinical information enables the correct diagnosis and therapy for the majority of cerebral space-occupying lesions. Some important differential diagnoses, e. g. low vs. high-grade tumors, require additional MRI methods. OBJECTIVE: This article critically discusses the importance of magnetic resonance spectroscopy (1H-MRS) in brain tumors. MATERIAL AND METHODS: The concentration of normal and pathological brain metabolites can be non-invasively measured by 1H-MRS. It is based on the principle that chemical proton compounds of certain brain metabolites focally attenuate the external magnetic field and change the proton resonance frequency according to typical patterns. In addition, parameter maps of MRS imaging (MRSI) can show the tumor heterogeneity as well as changes in the surrounding brain tissue. In this context, the patterns of N­acetylaspartate, total choline (tCho) and creatine are relatively robust, whereas the patterns of other metabolites, such as myoinositol, glutamate, lactate or lipids greatly depend on the external field strength and echo time. RESULTS: The signal intensity of tCho in vital tumor tissue increases with the WHO grade of the brain tumor, i.e. increases with the level of malignancy. The use of MRSI facilitates the WHO grading of gliomas by determining target points in biopsies. Different distribution patterns and specific metabolite signals enable a better differentiation between abscesses, metastases, central nervous system (CNS) lymphomas and gliomas. CONCLUSION: The use of 1H-MRS provides valuable information on the differential diagnosis and graduation of brain tumors; however, so far artefacts, signal strength, parameter selection and a lack of standardization impede the establishment of 1H-MRS for use in clinical routine diagnostics.

Post-Surgical Language Reorganization Occurs in Tumors of the Dominant and Non-Dominant Hemisphere.

PURPOSE: Surgical resection of brain tumors may shift the location of cortical language areas. Studies of language reorganization primarily investigated left-hemispheric tumors irrespective of hemispheric language dominance. We used functional magnetic resonance imaging (fMRI) to investigate how tumors influence post-surgical language reorganization in relation to the dominant language areas. METHODS: A total of, 17 patients with brain tumors (16 gliomas, one metastasis) in the frontotemporal and lower parietal lobes planned for awake surgery underwent pre-surgical and post-surgical language fMRI. Language activation post-to-pre surgery was evaluated visually and quantitatively on the statistically thresholded images on patient-by-patient basis. Results were qualitatively compared between three patient groups: temporal, with tumors in the dominant temporal lobe, frontal, with tumors in the dominant frontal lobe and remote, with tumors in the non-dominant hemisphere. RESULTS: Post-to-pre-surgical distributions of activated voxels changed in all except the one patient with metastasis. Changes were more pronounced in the dominant hemisphere for all three groups, showing increased number of activated voxels and also new activation areas. Tumor resection in the dominant hemisphere (frontal and temporal) shifted the activation from frontal towards temporal, whereas tumor resection in the non-dominant hemisphere shifted the activation from temporal towards frontal dominant areas. CONCLUSION: Resection of gliomas in the dominant and in the non-dominant hemisphere induces postsurgical shifts and increase in language activation, indicating that infiltrating gliomas have a widespread influence on the language network. The dominant hemisphere gained most of the language activation irrespective of tumor localization, possibly reflecting recovery of pre-surgical tumor-induced suppression of these activations.

Therapy of leptomeningeal metastasis in solid tumors.

Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.

[Towards more precision in the therapy of brain tumors. Possibilities and limits of MRI]. / Auf dem Weg zu mehr Präzision in der Hirntumortherapie : Möglichkeiten und Grenzen der MR-Bildgebung.

Due to the introduction of advanced functional and spectroscopic magnetic resonance (MR) sequences, MR imaging has gained significant importance in neuro-oncology. In contrast to recent years when neuro-oncological imaging was mostly limited to contrast-enhanced T1-weighted images, advanced MR methods provide direct visualization and assessment of tumor pathophysiology. This article summarizes the most relevant MR methods for neuro-oncological imaging and highlights the pathophysiological background as well as potential clinical applications. Ultimately, this article gives a glimpse into the future and introduces potential applications of ultra-high field MRI.

[Interdisciplinary neuro-oncology: part 1: diagnostics and operative therapy of primary brain tumors]. / Interdisziplinäre Neuroonkologie : Teil 1: Diagnostik und operative Therapie primärer Gehirntumoren.

By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function is increasingly feasible. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

[Interdisciplinary neuro-oncology: part 2: systemic therapy of primary brain tumors]. / Interdisziplinäre Neuroonkologie : Teil 2: Systemtherapie primärer Gehirntumoren.

By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function has become dramatically more extensive. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

Differential diagnosis of white matter lesions: Nonvascular causes-Part II.

The knowledge of characteristic lesion patterns is important in daily practice imaging, as the radiologist increasingly is required to provide precise differential diagnosis despite unspecific clinical symptoms like cognitive impairment and missed elaborated neurological workup. This part II dealing with nonvascular white matter changes of proven cause and diagnostic significance aimed to assist the evaluation of diseases exhibiting lesions exclusively or predominantly located in the white matter. The etiologies commented on are classified as follows: (a) toxic-metabolic, (b) leukodystrophies and mitochondriopathies, (c) infectious, (d) neoplastic, and (e) immune mediated. The respective mode of lesion formation is characterized, and typical radiological findings are displayed. More or less symmetrical lesion patterns on the one hand as well as focal and multifocal ones on the other are to be analyzed with reference to clinical data and knowledge of predilection sites characterizing major disease categories. Complementing spinal cord imaging may be useful not only in acute and relapsing demyelinating diseases but in certain leukodystrophies as well. In neuromyelitis optica (NMO), the detection of a specific antibody and some recently published observations may lead to a new understanding of certain deep white matter lesions occasionally complicating systemic autoimmune disease.

The U sign: tenth landmark to the central region on brain surface reformatted MR imaging.

BACKGROUND AND PURPOSE: Identification of the central region is of special importance to avoid neurologic deficits in brain surgery. Brain surface reformatted images (Mercator view) map the frontoparietal brain surface in 1 view and provide a synopsis of the most important landmarks. In this view, the U-shaped subcentral gyrus appears as a distinctive anatomic structure enclosing the Sylvian end of the central sulcus. The purpose of this study was to add the subcentral gyrus as a new landmark to the central region (U sign) and to compare its frequency and applicability with common landmarks in healthy hemispheres. MATERIALS AND METHODS: Mercator views of 178 hemispheres in 100 patients were generated from 3D MR imaging datasets. The hemispheres were evaluated on Mercator views for the presence or absence of each of the 9 common landmarks and the new U sign identifying the central region. RESULTS: The new landmark U sign was most common (96.6%), followed by the thin postcentral gyrus sign (95.5%). The least common landmark was the Ω-shaped handknob (54.5%). None of the landmarks could be identified in all hemispheres. All landmarks could be identified bilaterally in only 1.3% of patients. CONCLUSIONS: On the Mercator view, the new U sign is an applicable and even the most frequent landmark to identify the central region. Considering the variability of the anatomic structures of the brain, including the motor hand area, the synopsis of all 10 landmarks on this surface-reformatting projection is a helpful adjunct to standard MR imaging projections to identify the central region.

Cutoff value of choline concentration reliably reveals high-grade brain tumors among other contrast-enhancing brain lesions.

BACKGROUND AND AIM: To evaluate whether there is a cutoff value for a metabolite concentration measured by 1 H MR spectroscopy (MRS), which can be used to differentiate malignant brain tumors (high-grade gliomas, primary CNS lymphomas [PCNSL] and metastases) from other contrast-enhancing lesions like low-grade gliomas and non-neoplastic lesions. MATERIAL AND METHODS: 1 H MRS was performed in 252 consecutive patients with space-occupying brain lesions which were enhanced with application of a contrast agent. Concentrations of N-acetyl-aspartate, total creatine, choline containing metabolites (total choline, tCho), lipids, and lactate were evaluated from the contrast-enhancing part of the lesions and from the normal appearing brain tissue. Linear discriminant analysis was used to find the best predictor for malignant brain tumors. In addition, receiver operating characteristic analysis (ROC) was performed to determine a cutoff value for the best predictor in detecting malignant brain tumors with a specificity of >95%. RESULTS: All brain tumors and 20 out of 47 nonneoplastic lesions were examined histopathologically. The remaining 27 diagnoses were based on MR imaging, clinical findings, and follow-up. The final diagnosis was 134 high-grade gliomas (WHO grade III/IV), 36 metastases, 9 PCNSL, 8 low-grade gliomas (WHO grade I/II), 34 infections, 9 infarctions, 2 hematomas, and 2 vasculitides. 18 patients were excluded due to insufficient spectral quality. The tCho concentration was the best predictor to differentiate malignant brain tumors from enhancing low-grade gliomas or non-neoplastic lesions (F=26.6 [df: 25.833], p<0.0005). The ROC revealed that a cutoff tCho value, based on an increase of ≥40% compared to normal, yielded a specificity of 100% and a sensitivity of 89.4% to correctly diagnose a malignant brain tumor. CONCLUSION: 1 H MRS reliably differentiates malignant brain tumors from other contrast-enhancing brain lesions. At least a 40% increase of tCho compared to normal brain tissue indicates a malignant tumor (WHO grade III/IV gliomas, PCNSL, metastases) with >90% specificity and sensitivity.

Neuroradiological viewpoint on the diagnostics of space-occupying brain lesions.

Conventional magnetic resonance (MR) imaging of space-occupying lesions may answer most of the questions concerning the diagnosis and subsequent treatment strategies if patient age, clinical and paraclinical findings are considered as well. However, crucial and relevant differential diagnoses require additional MR methods, such as diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and magnetic resonance spectroscopy (MRS). In necrotic ring-enhancing lesions DWI may detect inflammatory processes, whereas characteristics of the peritumoral area may help to distinguish between metastases and glioblastomas. In solid tumors DWI, PWI and MRS may also aid the differentiation between low-grade gliomas and malignant tumors, such as gliomas WHO (World Health Organization) grade III and IV and lymphomas. This review briefly explains special MR methods with respect to brain tumors and illustrates the diagnostic pathways necessary for supplying a reliable diagnosis as well as optimal pre-operative imaging of space-occupying brain lesions.

MR imaging of midbrain pathologies.

The spectrum of pathologic processes affecting the midbrain features some differences to other brain areas. The midbrain is exposed to traumatic alterations due to its position between the tentorial edges, and some neurodegenerative and metabolic-toxic diseases may typically involve the midbrain. Isolated midbrain ischemia is rare, whereas the midbrain is typically part of the "top of the basilar" syndrome. Primary midbrain tumors are also infrequent and often show a benign clinical course. Apart from multiple sclerosis other inflammatory autoimmune processes and some infectious agents predominantly affect the brainstem including the midbrain. This review discusses the different pathologic processes of the midbrain, i.e., infarction, hemorrhage and trauma, inflammation, toxic and metabolic diseases, neurodegeneration, neoplastic diseases, as well as pathologies typically involving the perimesencephalic cisterns.

Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites.

Methotrexate (MTX)-associated myelopathy is a rare but serious subacute complication of MTX-based chemotherapy. We report the case of a woman with breast cancer and meningeal carcinomatosis who developed severe progressive myelopathy after four cycles of intrathecal MTX administration. We substituted high doses of the key metabolites of the methyl-transfer pathway: S-adenosylmethionine (SAM), 200 mg three times daily i.v.; folinate, 20 mg four times daily i.v.; cyanocobalamin, 100 microg once daily i.v.; and methionine, 5 g daily p.o. The patient's paraparesis improved rapidly thereafter, and magnetic resonance (MR) imaging showed resolution of the intramedullary lesions. Genetic analyses revealed homozygosity for the A allele of methylenetetrahydrofolate reductase (MTHFR) c.1298A>C (p.E429A), whereas other genetic variants of folate/methionine metabolism associated with MTX neurotoxicity were not present. Substitution with multiple folate metabolites may be a promising strategy for the treatment of MTX-induced neurotoxicity.