MRI Criteria Research Articles

Use of multiple biomarkers to improve the prediction of multiple sclerosis in patients with clinically isolated syndromes

Background: The early identification of patients at high risk of Clinically Definite Multiple Sclerosis (CDMS) represents the main purpose of diagnostic criteria and of clinicians in everyday clinical practice. Objective: To investigate whether the incorporation of different biomarkers in a model with established MRI criteria improves the prediction of MS. Methods: We evaluated baseline clinical data as well as MRI, multimodal evoked potentials and cerebrospinal fluid (CSF) data of patients with a first demyelinating episode. We used discrimination and calibration characteristics and reclassification of risk categories to assess incremental utility of different biomarkers for CDMS prediction. Results: During follow-up (median 7.2 years), 127 of the 243 participants in our study (mean age 31.6 years) developed a second clinical attack (CDMS). In Cox proportional-hazards models adjusted for established MRI criteria, age at onset, number of T1 lesions and presence of CSF oligoclonal bands significantly predicted the risk of developing MS within 2 and 5 years. The C-statistic increased significantly when the three biomarkers were incorporated into a model with established MRI criteria, both at 2 years (C-statistic with biomarkers vs. without biomarkers, 0.74 vs. 0.69) and at 5 years (0.66 vs. 0.70). The use of multiple biomarkers led to a 29% net-reclassification improvement at 2 years (p < 0.001) and 30% at 5 years (p < 0.001). Conclusions: The simultaneous addition of several biomarkers improves the risk stratification for MS in patients with clinically isolated syndromes beyond that of a model that is based only on MRI criteria.

Use of Preoperative MRI to Select Candidates for Local Excision of MRI-Staged T1 and T2 Rectal Cancer: Can MRI Select Patients With N0 Tumors?

To minimize the recurrence rate after local excision of rectal cancer, the false-negative rate of nodal staging should be minimized. The purpose of this study was to develop a set of criteria using preoperative MRI that would minimize the false-negative rate for the diagnosis of regional lymph node metastasis. A prospectively maintained colorectal cancer database and MRI images were retrospectively reviewed. This study was conducted at a multidisciplinary tertiary center. A total of 246 consecutive patients who underwent MRI and curative-intent surgery for MRI-staged T1/T2 rectal cancer from January 2008 to July 2012 were included. MRI features significantly associated with lymph node metastasis were identified using a χ test. Five diagnostic criteria for lymph node metastasis were created based on these predictive MRI features, and their false-negative rates were compared using the generalized estimating equation method. Small size/homogeneity of lymph nodes and no visible tumor/partially involved muscular layer were significantly associated with lower risks of lymph node metastasis. When tumor invasion depth was not considered, the false-negative rate did not decrease below 10%, even when the strictest criterion for morphologic evaluation of lymph nodes (not visible or <3 mm) was used. Adding invasion depth to the diagnostic criteria significantly decreased the false-negative rate as low as 1.8%. This study is limited by its small sample size and retrospective nature. Assessing both the depth of tumor invasion and lymph node morphology may reduce the false-negative rate and can be helpful to better identify candidates suitable for local excision of early stage rectal cancer. However, strict MRI criteria for oncologic safety might result in considerable false-positive cases and limit the application of local excision.

Mri and ct criteria for Alzheimer's disease stages diagnostics

Mri and ct criteria for Alzheimer's disease stages diagnostics

Subcategorization of Suspicious Breast Lesions (BI-RADS Category 4) According to MRI Criteria: Role of Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging

The purposes of this study were to investigate whether dynamic contrast-enhanced MRI is adequate for subcategorization of suspicious lesions (BI-RADS category 4) and to evaluate whether use of DWI improves diagnostic performance. The study group was composed of 103 suspicious lesions found in 83 subjects. Patient ages and lesion sizes were compiled, and two radiologists reanalyzed the images; subcategorized the findings as BI-RADS 4A, 4B, or 4C; and calculated apparent diffusion coefficient (ADC) values. The stratified variables were tested by univariate analysis and inserted in two multivariate predictive models, which were used to generate ROC curves and compare AUCs. Positive predictive values (PPVs) for each subcategory and ADC level were calculated, and interobserver agreement was tested. Forty-four (42.7%) suspicious findings proved malignant. Except for age (p = 0.08), all stratified predictor variables were significant in univariate analyses (p < 0.01). Logistic regression models did not differ substantially after comparison of the ROC curves (p = 0.09), but the one including ADC values was slightly better: AUC of 0.89 (95% CI, 0.82-0.95) against AUC of 0.85 (95% CI, 0.78-0.93). PPV increased progressively in each BI-RADS 4 subcategory (4A, 0.15; 4B, 0.37; 4C, 0.84). ADC values of 1.10 × 10(-3) mm(2)/s or less had the second highest PPV (0.77). Interobserver agreement was substantial at a kappa value of 0.80 (95% CI, 0.70-0.90; p < 0.01). Risk stratification of suspicious lesions (BI-RADS category 4) can be satisfactorily performed with DCE-MRI and slightly improved when DWI is introduced.

Altered PLP1 splicing causes hypomyelination of early myelinating structures.

ObjectiveThe objective of this study was to investigate the genetic etiology of the X-linked disorder “Hypomyelination of Early Myelinating Structures” (HEMS).MethodsWe included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients’ fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs.ResultsAll patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20 alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved in regulating PLP1/DM20 alternative splicing. Splicing studies in fibroblasts and transfected cells confirmed a decreased PLP1/DM20 ratio.InterpretationBrain structures that normally myelinate early are poorly myelinated in HEMS, while they are the best myelinated structures in Pelizaeus–Merzbacher disease, also caused by PLP1 alterations. Our data extend the phenotypic spectrum of PLP1-related disorders indicating that normal PLP1/DM20 alternative splicing is essential for early myelination and support the need to include intron 3 in diagnostic sequencing.

OP49 – 2560: PLP1 mutations affecting PLP1/DM20 alternative splicing causes hypomyelination of early myelinating structures

Objectives Inherited leukodystrophies represent a diagnostic challenge, as many patients remain without definitive diagnosis. In this study we investigated the genetic etiology of the recently described X-linked childhood disorder “Hypomyelination of Early Myelinating Structures” (HEMS). In HEMS, brain structures normally myelinating early, are hypomyelinated, which is in contrast to known hypomyelination disorders, like Pelizaeus-Merzbacher disease (PMD). Methods We included patients diagnosed with HEMS by brain MRI criteria and affected siblings. Exome sequencing was used to search for causal mutations in 16 patients of 10 families. In silico analysis of effects of the mutations on splicing and secondary RNA folding was performed. Also, gene splicing was examined in RNA prepared from patients' fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. Results All patients had unusual hemizygous mutations in a specific region of the PLP1 gene. These mutations were located in exon 3B (2 silent, 1 missense and 1 deletion), which is splice out in isoform DM20 or in intron 3 outside the splice donor sequence (5 mutations). Four mutations are located deep in intron 3; a region that is not sequenced with Sanger sequencing. These mutations effect the secondary PLP1 RNA structure and decreased the PLP1/DM20 ratio. The other mutations, except for the deletion that truncated PLP1 but not DM20, were also predicted to alter PLP1/DM20 alternative splicing. Splicing studies in fibroblasts' and transfected cells confirmed a decreased PLP1/DM20 ratio. Conclusions We show that specific mutations in the PLP1 gene cause a hypomyelination pattern which contrasts the pattern seen in PMD, also caused by PLP1 mutations. This indicates that the PLP1/DM20 ratio influences early myelination. The mutations present in HEMS patients provide a challenge for PLP1 diagnostic sequencing and support the need to include intron 3.

Update on clinically isolated syndrome

Optic neuritis, myelitis and brainstem syndrome accompanied by a symptomatic MRI T2 or FLAIR hyperintensity and T1 hypointensity are highly suggestive of multiple sclerosis (MS) in young adults. They are called "clinically isolated syndrome" (CIS) and correspond to the typical first multiple sclerosis (MS) episode, especially when associated with other asymptomatic demyelinating lesions, without clinical, radiological and immunological sign of differential diagnosis. After a CIS, the delay of apparition of a relapse, which corresponds to the conversion to clinically definite MS (CDMS), varies from several months to more than 10 years (10-15% of cases, generally called benign RRMS). This delay is generally associated with the number and location of demyelinating lesions of the brain and spinal cord and the results of CSF analysis. Several studies comparing different MRI criteria for dissemination in space and dissemination in time of demyelinating lesions, two hallmarks of MS, provided enough substantial data to update diagnostic criteria for MS after a CIS. In the last revision of the McDonald's criteria in 2010, diagnostic criteria were simplified and now the diagnosis can be made by a single initial scan that proves the presence of active asymptomatic lesions (with gadolinium enhancement) and of unenhanced lesions. However, time to conversion remains highly unpredictable for a given patient and CIS can remain isolated, especially for idiopathic unilateral optic neuritis or myelitis. Univariate analyses of clinical, radiological, biological or electrophysiological characteristics of CIS patients in small series identified numerous risk factors of rapid conversion to MS. However, large series of CIS patients analyzing several characteristics of CIS patients and the influence of disease modifying therapies brought important information about the risk of CDMS or RRMS over up to 20 years of follow-up. They confirmed the importance of the initial MRI pattern of demyelinating lesions and of CSF oligoclonal bands. Available treatments of MS (immunomodulators or immunosuppressants) have also shown unequivocal efficacy to slow the conversion to RRMS after a CIS, but they could be unnecessary for patients with benign RRMS. Beyond diagnostic criteria, knowledge of established and potential risk factors of conversion to MS and of disability progression is essential for CIS patients' follow-up and initiation of disease modifying therapies.

Criteria of ineffectiveness of treatment with first-line therapy: how to use MRI results in decision making?

The importance of MRI stuides in the control over treatment efficacy in multiple sclerosis and appropriate recommendations on drug substitution during treatment are discussed. We suggest low, middle or high risk in respect to the efficacy of current treatment. Accordingly, drug substitution can be related with the low level of fears for all three criteria or the moderate level for any two criteria or the high level for any one criterion. Since MRI criteria are important, this model appears to be the most rational because the physician can make a decision about treatment escalation if the patient has ≥3 new T2-lesions or ≥3 contrast-enhanced T1-lesions.

Can We Speak About a Psychiatric Attack During a Multiple Sclerosis?

Introduction:Psychiatric disorders may be encountered in certain central nervous system diseases. In multiple sclerosis (MS) some of these manifestations have been described and are not necessarily related to the psychological impact of such disabling disease. The link between these disorders and MS remains incompletely determinated. Case report: We report a case of a 31 years old women, diagnosed since March 2010 for MS. She developed two neurological episodes: retrobulbar optic neuritis and lower limb paresthesia. She fulfilled Barkhof's MRI criteria. The new episode was associated with concomitant melancholia and symptoms. Brain magnetic resonance imaging revealed a new frontal lesion. Biological balance was normal. The diagnosis of MS was established. Given to treat acute episodes, high-dose corticosteroids enabled regression of the psychological fits. Discussion: Psychiatric disorders in MS have been described since 1926. Patients may have mood disorders, personality disorders or psychosis. Thus, the occurrence of disorder during the MS is no longer regarded as an atypical subject. They seem to occur on average one year after diagnosis of MS. More rarely, they can usher the clinical picture. The possibility of isolated psychiatric attack in MS cannot be excluded. Hypothesis reinforced by the good response of symptoms to steroids and the presence of a concomitant gadolinium enhancing lesion. Conclusion: This case report adds to those in the literature, making disorder a possible manifestation of MS. The symptoms-MS association may be due to local MS-related brain damage or a common genetic susceptibility.

Differential diagnosis of MS

Diagnostic criteria for MS rely on the demonstration of CNS disease in space and time and in reasonable exclusion of other causes. Since McDonald 2001, in patients with a first attack, MRI may provide evidence of diagnosis for dissemination in space and time. The 2010 McDonald criteria selected the Magnims criteria for dissemination in space (DIS). DIS is defined as the presence of ≥1 asymptomatic T2 lesion(s) in at least two of four locations considered characteristic for MS in previous MRI criteria: juxtacortical, periventricular, infratentorial and spinal cord. These criteria simplify the previous Barkhof criteria and highlight the importance of lesion location for MS diagnosis. Moreover, this new definition relies on T2 lesions only. Non-inclusion of gadolinium enhancing lesions seems appropriate since enhancing lesions per se provide information on disease activity and not on dissemination in space. For demonstration of dissemination in time (DIT), an MRI performed at any time demonstrating DIS and showing at least one or more asymptomatic gadolinium enhancing and non-enhancing lesions(s) (this being used as evidence for DIT) would be sufficient to diagnose MS. Although many studies have already shown the importance of CSF study in the diagnosis and differential diagnosis of MS, the presence of oligoclonal bands has not been included in the diagnosis algorithm. These criteria have been adapted to other populations such as patients with primary progressive MS or patients with paediatric MS. An overview of the past diagnostic criteria will also be performed as well as new directions for the future will be considered (intracortical lesions, 3 T MRI, other). One of the problems of the diagnosis of MS is that we should rule out other conditions and this is not always an easy task. Clinical cases to illustrate differential diagnoses will be presented.

Listeria Brainstem Encephalitis in Small Ruminants: Correlation of Magnetic Resonance Imaging and Histopathology.

Listeria Brainstem Encephalitis in Small Ruminants: Correlation of Magnetic Resonance Imaging and Histopathology Christina Stahl1, Anna Oevermann2, Daniela Gorgas1 1Clinical Radiology, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Switzerland 2Neurocenter, Department of Clinical Research and Veterinary Public Health, Vetsuisse-Faculty, University of Bern, Switzerland Abstract Brainstem encephalitis is an intriguing form of Listeria monocytogenes central nervous system (CNS) infection in humans and ruminants and has a high fatality rate. However, intra vitam diagnosis remains difficult in both species (1, 2). We performed MRI of affected small ruminants, in which Listeria brainstem encephalitis is a common CNS disease, and correlated MRI features with histopathology in order to define MRI criteria for the diagnosis of listeria brainstem encephalitis. Fifteen small ruminants (nine sheep, six goats) with listeriosis underwent MRI examination of the brain using a 0.3 T system (five animals) and 1.0 T system (ten animals) including T2w, FLAIR and T1w sequences pre and post Gadolinium administration. Listeria brainstem encephalitis was confirmed by histopathology, and histopathological changes were correlated to MRI features. On MRI, lesions were best visualized in T2-weighted sequences. In all animals they were characterized by asymmetric increased signal intensity in the rhombencephalon in T2w and FLAIR sequences. The lesions showed a variable pattern and distribution, ranging from patchy with ill defined borders to diffusely affecting the entire cross-sectional area of the brainstem. Few animals had lesions in the diencephalon (three animals), whilst histopathologically detectable lesions commonly extended to the diencephalon and involved cranial nerve roots (twelve animals). The lesions were iso- to mildly hypointens in T1w sequence. Mild to moderate patchy or ring-like contrast uptake was observed in the rhombencephalon of five animals (one sheep, four goats), which showed vascular damage and perivascular fibrin accumulation on light microscopy. In the brainstem, the asymmetric T2-hyperintense lesions observed by MRI correlated well with the inflammatory infiltrates observed in histopathology (3). However, lesions in the diencephalon, cranial nerves and meninges of rostral brain areas were rarely detected by MRI, indicating that MRI underestimates involvement of the rostral brain and brain associated structures. Contrary to reported human cases of neurolisteriosis (4), contrast uptake was an inconsistent finding occurring in the rhombencephalon of only five animals.

Idiopathic inflammatory demyelinating disease of the central nervous system in patients with inflammatory bowel disease: retrospective analysis of 9095 patients

Anti-TNFα biologics induce and maintain remission in inflammatory bowel disease (IBD). Also, they have been reported to induce or unmask idiopathic inflammatory demyelinating disease of the central nervous system (IIDD). To determine if anti-TNFα biologics increased the risk of IIDD in a large cohort of patients with IBD. We retrospectively identified adult patients referred to the Mayo Clinic, Rochester, MN for management of IBD from a five state capture area (Minnesota, Wisconsin, North Dakota, South Dakota and Iowa) between 1996 and 2010. IIDDs were identified in both Crohn's disease (CD) and ulcerative colitis (UC) patients with and without anti-TNFα exposure using the 2010 McDonald MRI criteria. The risk of IIDDs in patients with and without anti-TNFα exposure was estimated for IBD; CD and UC groups separately. A total of 9095 patients with IBD were identified (4342 CD and 4753 UC). Four patients with CD with exposure to anti-TNFα agents (4/2054) and five patients with CD without anti-TNFα exposure (5/2288) developed a confirmed IIDD. One patient with UC with exposure to anti-TNFα agents (1/1371) and five patients with UC without anti-TNFα agents developed a confirmed IIDD (5/3382). The per cent of IIDDs in patients with and without anti-TNFα exposure was; IBD: 0.15% and 0.18% (RR=0.83, 95% CI: 0.28-2.42; P=0.729); CD: 0.19% and 0.22% (RR=0.89, 95% CI: 0.24-3.31; P=0.863); UC: 0.07% and 0.15% (RR=0.49, 95% CI: 0.06-4.22; P=0.510). Anti-TNFα biologics do not appear to impact the risk of developing clinical idiopathic inflammatory demyelinating disease in patients with inflammatory bowel disease.

O8.04 * TEMOZOLOMIDE AFTER RADIOTHERAPY IN RECURRENT "LOW-GRADE" DIFFUSE BRAINSTEM GLIOMA IN ADULTS

Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is usually considered to be the standard treatment. However, the role of chemotherapy in treating relapses after RT is unclear, and this study aimed to assess the use of temozolomide (TMZ) in this situation. We conducted a retrospective analysis of patients from our database with “low grade” adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT. The patients were diagnosed by histology or MRI criteria compatible with a low-grade glioma. The tumors were localized in the pons, medulla oblongata or midbrain, excluding supratentorial or infratentorial tumors that had infiltrated the brainstem secondarily. The patients’ clinical and radiological responses were assessed, and their progression free survival (PFS) and overall survival (OS) time were estimated. Fifteen adult patients (median age 34 years) fulfilled the inclusion criteria. Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment and had a median PFS of 34.2 months (95 % CI 24.1–44.2). The median KPS at the time of relapse was 80. TMZ was administered orally at 150–200 mg/m2 for 5 days, every 28 days. Clinical improvement after TMZ was observed in 9 cases (60 %), whereas radiological assessment detected responses in 6/15 cases, including 4 partial and 2 minor responses. The estimated median PFS after TMZ was 9.5 months (95 % CI 7.9–11), and the median OS was 14.4 months (95 % CI 10.5–18.2). Grade 3 thrombopenia was observed in 26 % of cases. TMZ could be useful after RT failure in adult patients with recurrent diffuse “low grade” brainstem glioma.

Revised McDonald criteria for multiple sclerosis diagnostics in Central Russia: Sensitivity and specificity

Background: The 2010 revised McDonald criteria were developed with data gathered from Caucasian European and North American populations, and their applicability has been questioned for the Russian population. Objective: The objective of this report is to compare the specificity, accuracy, sensitivity and predictive value of MRI criteria incorporated to the new (2010) and old (2005) McDonald criteria for early multiple sclerosis (MS) diagnostics in the Nyzhnyi Novgorod (Russia) population. Methods: A total of 103 patients with symptoms suggestive of MS were recruited from 2008 to 2011 retrospectively. Patients were followed up until MS was confirmed or other proved diagnoses were determined. Their baseline and follow-up brain and spinal cord MRIs were retrospectively evaluated. Sixty-two patients (60%) converted to MS during the follow-up period (mean in 11±4.2 months). Results: In 41 cases (38%) diagnoses another than MS were established. The sensitivity, specificity, accuracy, PPV and NPV of the revised MRI criteria were 74%, 93%, 82%, 94%, 70%, respectively. Conclusions: Despite the limitations of our study, we conclude that the ability of the revised MRI criteria for early MS diagnostics in the Russian population is approximately similar to that determined by the international panel in Europe.

Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma in adults.

Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is usually considered to be the standard treatment. However, the role of chemotherapy in treating relapses after RT is unclear, and this study aimed to assess the use of temozolomide (TMZ) in this situation. We conducted a retrospective analysis of patients from our database with "low grade" adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT. The patients were diagnosed by histology or MRI criteria compatible with a low-grade glioma. The tumors were localized in the pons, medulla oblongata or midbrain, excluding supratentorial or infratentorial tumors that had infiltrated the brainstem secondarily. The patients' clinical and radiological responses were assessed, and their progression free survival (PFS) and overall survival (OS) time were estimated. Fifteen adult patients (median age 34years) fulfilled the inclusion criteria. Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment and had a median PFS of 34.2months (95% CI 24.1-44.2). The median KPS at the time of relapse was 80. TMZ was administered orally at 150-200mg/m(2) for 5days, every 28days. Clinical improvement after TMZ was observed in 9 cases (60%), whereas radiological assessment detected responses in 6/15 cases, including 4 partial and 2 minor responses. The estimated median PFS after TMZ was 9.5months (95% CI 7.9-11), and the median OS was 14.4months (95% CI 10.5-18.2). Grade 3 thrombopenia was observed in 26% of cases. TMZ could be useful after RT failure in adult patients with recurrent diffuse "low grade" brainstem glioma.

Diagnostic validity (sensitivity and specificity) of panoramic X-rays in osteoarthrosis of the temporomandibular joint

Objective:To establish the diagnostic validity of panoramic X-rays (PRx) in temporomandibular osteoarthrosis (OA) using the clinical and imaging criteria (magnetic resonance imaging, MRI) of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) as gold standards.Methods:Eighty-four patients with full clinical records (RDC/TMD), PRx, and MRI scans were selected. Two stomatologists evaluated the PRx for OA. The MRI findings were derived from the radiologist report. Intra/inter-examiner concordance was established. The diagnostic concordance between clinical signs and MRI was determined. Both were used as gold standards to calculate the validity of PRx in OA.Results:The diagnostic validity of PRx with MRI as gold standard was sensitivity = 69·0% and specificity = 67·9%. The diagnostic validity of PRx with clinical criteria as gold standard was sensitivity = 61·6% and specificity = 57·9%.Discussion:Panoramic X-rays have scant diagnostic validity in temporomandibular osteoarthrosis when taking MRI or clinical criteria of RDC/TMD as gold standards.

MRI criteria for the diagnosis of pleomorphic adenoma: a validation study

ObjectivesTo validate an MRI algorithm characteristic of pleomorphic adenoma (PA). Study designCross-sectional analysis. SettingAcademic tertiary-care medical center. MethodsA radiologic algorithm for the MRI diagnosis of PA was developed on the basis of five “high probability” criteria that all must be fulfilled for the MRI to qualify as a positive test result: bright T2-signal, sharp margins, heterogeneous nodular enhancement, lobulated contours, T2-dark rim. We then identified MRI images from our institutional database to test the diagnostic accuracy of the proposed algorithm. ResultsA total of 103 parotidectomy cases with adequate MRI studies were identified (pleomorphic adenoma n=41, mucoepidermoid carcinoma n=11, Warthin's tumor n=8, adenoid cystic carcinoma n=6, oncocytoma n=6, acinic cell carcinoma n=5, salivary duct carcinoma n=5, and other n=21). Eighteen of 21 cases that met all five “high probability” MRI criteria were consistent with PA on final histopathology; 3 were consistent with carcinoma. MRI had a specificity of 95.1% [95% confidence interval: 85.6–98.7%] and sensitivity of 43.9% [95% C.I.: 28.8–60.1%] for PA. The positive predictive value was 85.7% [95% C.I.: 70.4–100%] and the negative predictive value was 71.9% [95% C. I.: 62.0–81.9%]. The overall diagnostic accuracy was 74.8% [95% C.I.: 66.2–83.3%]. ConclusionA “high probability” MRI is about 95% specific for pleomorphic adenoma. A subset of patients with MRI imaging that is highly suggestive of PA may reliably avoid further workup. The value of MRI in this setting is especially useful if preoperative fine needle aspiration is not readily available. A significant proportion of PAs, however, have indeterminate imaging features that overlap considerably with other benign and malignant lesions.

FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA. A POETIC CONSORTIUM TRIAL

BACKGROUND: Purpose: The ras/raf signaling pathway is crucial in the development of pediatric low-grade gliomas (LGGs). Aberrant ras/raf signaling is involved in tumorigenesis through promotion of cell proliferation, survival, and differentiation in sporadic LGG. Everolimus (RAD001) is a potent and selective inhibitor of mTOR, a downstream element of the ras/raf pathway. The activity, safety and pharmacokinetics of everolimus in pediatric patients with radiographic recurrent/progressive LGG are presented. METHODS: Pediatric patients with radiographic progressive or recurrent LGGs without neurofibromatosis type I were treated with oral everolimus 5mg/m2/dose once daily. Therapy was provided for 28 days (one cycle) and could be repeated for a total of 12 cycles. Response, as determined by standard 2-D MRI criteria, was assessed for all patients. Pharmacokinetics, pharmacogenetics, pharmacodynamic parameters including inhibition of p70s6 kinase activity, 4E-BP1 phosphorylation inhibition and suppression of cMyc expression, as well as the toxicity profile of everolimus were evaluated. RESULTS: Twenty-three patients with a median age of 9 years (range, 3–17 years) were enrolled, all of whom had received prior chemotherapy (average # regimens = 2.7) including progression after a carboplatin-containing regimen. Median number of cycles of therapy was 10 (range, 1-12). Responses were determined by blinded central review and included 4 patients with PR (>50% decrease) and 13 with stable disease. Six patients had progressive disease by one year. Overall therapy was well tolerated; two patients discontinued therapy due to mouth sores (n = 1) and withdrawal of consent (n = 1). Everolimus PK parameters were similar to those previously reported in both adult and pediatric patients and drug trough levels were maintained above 5ng/ml. Pharmacodynamic analysis demonstrated inhibition of downstream targets of mTOR including phospho-S6 kinase, 4E-BP1 phosphorylation and cMyc expression within 14 days of initiation of everolimus therapy and this inhibition was maintained throughout the treatment period. CONCLUSIONS: Everolimus was well tolerated in pediatric patients with progressive or recurrent LGGs and demonstrated activity in this multiply recurrent/progressive patient population. Incorporation of everolimus into frontline LGG therapy is being proposed. SECONDARY CATEGORY: Clinical Neuro-Oncology.

Methotrexate use and liver disease - a causal relationship?

For patients with moderate-to-severe psoriasis, current guidelines recommend systemic treatment to achieve adequate disease control.1 Although more than 90 percent of dermatologists are aware of the national treatment guidelines for psoriasis2, less than 50 percent of patients with moderate-to-severe psoriasis receive systemic treatment3. A survey of dermatologists from Europe and Canada recently identified safety concerns as an important barrier to the use of methotrexate for psoriasis treatment.4

“Invisible” Brain Stem Infarction at the First Day

In specific stroke cases, serial diffusion-weighted magnetic resonance imaging (DW MRI) on day 1 was unable to show a lesion, whereas that on day 4 and later clearly revealed a lesion. However, clinical features of this phenomenon ("invisible" brain stem infarction [IBI] at the first day) have not been fully delineated. We retrospectively recruited 212 stroke patients in the Emergency Unit and Neurology Department. Among these, we studied patients with IBI. Definition of IBI is that acute and clear brain stem symptoms/signs on arrival were ameliorated at discharge and appearance of high signal intensity on serial DW images with low apparent diffusion coefficient (ADC) by 1.5T MRI with 2-mm slices. IBI were found in only 6 patients. Day 1 invisible stroke was found only in the brain stem (17%, 6 of 35) but none (0 of 177) in the hemispheric infarction (P<.05). In most patients with IBI, DW MRI turned out visible at the third/fourth day. Before the fourth day, DW/ADC signal changes in patients with IBI were minimal. In IBI, lesion size (mean 2.7mm(2)) was smaller than that of visible cases (mean 7.3mm(2)). In IBI, lesion location was mostly at the dorsolateral medulla. In IBI, sensory disturbance was significantly more common (67%) than visible cases (24%; P<.05), whereas dysarthria was less common (0%; P<.01) than visible cases (66%; P<.01). It is likely that patients with smaller stroke volume, sensory disturbance, and medullary location are prone to develop IBI. When evaluating stroke using MRI criteria, recognition of IBI is important to start early management.