Persisting Embryonal Infundibular Recess in Morning Glory Syndrome: Clinical Report of a Novel Association.

Morning glory syndrome is characterized by a congenital optic disc defect that resembles the eponymous flower. We present the MR imaging findings of 2 pediatric patients with morning glory disc anomaly and persisting embryonal infundibular recess, another rare malformative finding, a previously unreported association. Neuroradiologists should be aware of the possible presence of a persisting embryonal infundibular recess in patients with morning glory syndrome, to aid in the differential diagnosis including other pituitary malformations such as pituitary stalk duplication.

Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.

[Systemic treatment of brain metastases from breast cancer]. / Métastases cérébrales de cancer du sein: traitements systémiques.

An increase in the incidence of breast cancer patients with brain metastases has been observed over the last years, mainly because the recent development of new drugs including therapies targeting HER2 (human epidermal growth factor receptor 2) resulted in an increased survival of these patients. With HER2+ patients living longer and the well-known neurotropism of HER2+ tumour cells, the resulting high incidence of brain metastases is not really surprising. Moreover, brain metastases more often occur within a context of existing extracranial metastases. These need to be treated at the same time in order to favourably impact patients' survival. Consequently, the management of breast cancer patients with brain metastases clearly relies on a multidisciplinary approach, including systemic treatment. A working group including neuro-oncologists, neurosurgeons, radiation oncologists and oncologists was created in order to provide French national guidelines for the management of brain metastases within the "Association des neuro-oncologues d'expression française" (ANOCEF). The recommendations regarding the systemic treatment in breast cancer patients are reported here including key features of their management.

Widespread microstructural white matter involvement in amyotrophic lateral sclerosis: a whole-brain DTI study.

BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques to the study of ALS has undoubtedly improved our knowledge of disease pathophysiology, even if the actual spread of the neurodegenerative process throughout the central nervous system is not fully understood. The present study aimed to detect WM patterns of microstructural abnormalities to better investigate the pathologic process in ALS, within but also beyond CSTs, in a whole-brain analysis. MATERIALS AND METHODS: DTI was performed in 19 patients with ALS and 20 matched healthy controls, by using whole-brain TBSS and VOI analyses. RESULTS: We observed a significant decrease of FA in the body of CC of the ALS group (P < .05). At the VOI level, both FA decrease and RD increase in the body of CC significantly correlated with the UMN score (P = .003 and P = .02). Additionally, significant voxelwise positive correlations between FA and the ALSFRS-R were detected in the WM tracts underneath the left premotor cortex (P < .05). CONCLUSIONS: The correlations between reduction of FA and increase of RD in the body of CC with the UMN score indicate that the WM degeneration in the CC is strictly related to the ALS pyramidal impairment, while the correlation between FA and ALSFRS-R in the associative tracts underneath the left premotor cortex might reflect the progressive spread of the disease from the motor toward the extramotor areas.

Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer.

BACKGROUND: The purpose of this study was to evaluate the prognostic and predictive value of p27 expression in patients with early breast cancer. PATIENTS AND METHODS: Quantitative immunofluorescence assays for p27 were done on a tissue microarray that included 823 samples from patients randomized between anthracycline-based chemotherapy and no chemotherapy. Quantification of p27 was done using the AQUA® system (HistoRx, Inc., Branford, CT). Both p27 nuclear expression and the nuclear to cytoplasmic ratio were assessed. RESULTS: Nuclear p27 expression was not predictive for the efficacy of anthracycline-based chemotherapy [adjusted P=0.18 for disease-free survival (DFS)] nor prognostic [95% confidence interval (CI) 0.99-1.01, P=0.49]. However, p27 nuclear/cytoplasmic ratio was predictive for the efficacy of adjuvant chemotherapy (adjusted P=0.016 DFS). The adjusted hazard ratio (HR) for relapse associated with adjuvant chemotherapy was 0.56 (95% CI 0.37-0.84, P=0.005) and 1.06 (95% CI 0.76-1.47, P=0.74) for patients with high and low nuclear/cytoplasmic ratio, respectively. p27 N/C ratio was prognostic in patients treated with chemotherapy (HR for relapse or death for a 1 unit increase in p27 N/C ratio was 0.30, 95% CI 0.12-0.77) but not in the untreated arm (HR for relapse or death was 1.27, 95% CI 0.58-2.8). CONCLUSIONS: This study did not confirm the role of p27 nuclear expression as a prognostic parameter. However, the p27 nuclear/cytoplasmic ratio was predictive in patients treated with anthracycline-based chemotherapy.

Cervical chordoma. A case report and differential diagnosis.

Chordomas are rare and aggressive tumors derived from notochordal remnants, usually arising in the axial skeleton. The most frequently reported anatomic distribution of chordoma is 50% sacral, 35% spheno-occipital and 15% spinal. We describe the case of an elderly lady presenting with progressive dysphagia, headache and neck pain. We found an expansile mass extending from C1 to C3. While running the diagnostic plan we considered a variety of lesions possibly involving the cervical spine. Biopsy revealed the mass was a chordoma.

Giant dilatations of virchow-robin spaces in the midbrain. MRI aspects and review of the literature.

Virchow-Robin spaces are lesions often seen in the brain parenchyma but their etiopathogenesis remains unsettled. Giant Virchow-Robin spaces placed in the midbrain are extremely rare. We describe three patients with a diagnosis of giant Virchow-Robin spaces in the midbrain, and their clinical and radiologic findings. We reviewed the literature in terms of the etiopathology, anatomic and radiologic appearance and differential diagnosis of the giant Virchow-Robin spaces. The diagno-stic role of the high Tesla magnetic resonance devices and new sequences techniques such as three dimensional isotropic acquisition and diffusion tensor imaging were also evaluated in this case series.

Paget's Disease. A Case Report.

Paget's disease (PD) is a common focal progressive osteometabolic disorder characterised by a disturbance in bone modelling and remodelling, because of an increase in osteoblastic and osteoclastic activity. It is a condition of unknown aetiology affecting approximately 3% of the population over 40 years of age and, approximately 10% of those over the age of 85 years. It is most common in Northern Europe and Australia and is rare in Asia and Africa. We describe the case of a 71-year-old man diagnosed with PD confined to the sacrum. After laboratory test, an imaging study with radiography, scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) was performed disclosing findings compatible with Paget's disease in middle pathologic phase. The diagnosis was confirmed at biopsy. The structural modification of the sacrum with spongiosa rarefaction, thickening of bone and intact bone cortical, confirmed by CT, are tipical of an intermediate phase of PD. This was also supported by signal MRI changes showing substitution of the red by the fat medulla, visualized by FS sequences. Once the treatment for the bone disease was established, the patient no longer complained of pain. Special attention should be paid to male and elderly patients with pain in the lumbar spine because of the potential risk cancer development (21). The radiologist must be attentive to the possible presentations and complications of PD, even in uncommon sites, trying whenever possible to correlate the radiological features with the patient's clinical symptoms.

[Mechanisms of resistance to molecular targeted therapies in breast cancer: update and future]. / Mécanismes de résistance aux thérapeutiques moléculaires ciblées dans le cancer du sein : constats et perspectives.

The importance of targeted therapies has been emphasized by clinical trials using antiangiogenic or HER2 inhibitors in breast cancer. First with trastuzumab, it was demonstrated that targeted therapies may improve outcome in patients with HER overexpressing breast cancer in metastatic or adjuvant settings. The emerging role for angiogenesis inhibitors has also been demonstrated with bevacizumab. Unfortunately, there is growing clinical and biological evidence that tumour cells may develop unexpected and complex mechanisms of resistance to those targeted therapies. This review outlines the mechanisms by which tumour cells may resist to new targeted agents. Most recent developments are also highlighted.

Non-Alcoholic Wernicke Encephalopathy: MR Imaging and Review of the Literature.

We describe a patient with non-alcoholic Wernicke's encephalopathy caused by long-term parenteral nutrition. The diagnosis is based on clinical and magnetic resonance findings. We also reviewed the literature review in typical and atypical findings at MR examination.

Hippocampal asymmetry with hippocampal sulcus remnants in a patient with mild cognitive impairment. A case report.

A 65-year-old woman underwent MRI for a mild cognitive impairment (MCI) at Mini-Mental State Examination (MMSE). MRI showed hippocampal sulcus remnants bilaterally, although they were larger on the right, and left hippocampal atrophy with increased left fimbriosubicular distance (right side: 1.2 mm; left side: 2.0 mm). The meaning of these findings in relation to clinical aspects is discussed and reviewed according to data from the literature.

Spontaneous resolution of eosinophilic granuloma in a patient with a psychotic disorder.

A 16-year-old female who manifested psychotic symptoms underwent CT and MRI for the evaluation of an incidentally discovered asymptomatic palpable mass of the right occipital region of the skull. The correlation between clinical and radiological data and biopsy data led to the diagnosis of eosinophilic granuloma. The radiological finding is discussed and reviewed in relation to clinical aspects and literature data.

Role of Magnetic Resonance Imaging in Duane's Retraction Syndrome: Presence of the Abducens Nerve Depending on Type. A Clinical-Anatomical Study.

This study correlated anatomical findings and clinical evidence in Duane's Retraction Syndrome using brain MRI. The study included 11 patients with different types of Duane's Retraction Syndrome (DRS). Each patient underwent brain MRI. The VI(th) nerve was absent in all patients with DRS-I, present in all patients with DRS-II, while findings varied in patients with DRS-III. Our study confirms the literature on the usefulness of brain MRI in diagnosis of Duane's Retraction Syndrome in children.

[Prevalence of elevated serum CA 15-3 at time of metastatic relapse of breast cancer and correlation with hormone receptor status]. / Prévalence de l'élévation du CA 15-3 lors de la rechute métastatique des cancers du sein: corrélation avec l'expression des récepteurs hormonaux et de Her2.

CA15-3, a peptide derived from MUC-1, an hormonally-regulated protein, is the most widely used serum marker of breast cancer. CA15-3 level increases at the metastatic phase in 50-80% breast cancer patients. Although rise of CA15-3 precede symptoms of metastasis by a mean time of 2-9 months, current international guidelines do not recommend its routine use for screening for metastases because of moderate sensitivity and absence of clinical impact. We conducted a retrospective study among all patients with metastatic breast cancer seen by three senior breast oncologists during a 4-month period. We evaluated correlation of CA15-3 level at the time of metastatic relapse with ER, PgR and Her2 expressions, tumor type, size and nodal status at initial diagnosis, and sites of metastases. CA15-3 was increased in 168/272 patients (62%) at diagnosis of metastases. ER/PgR positivity was strongly correlated with elevated CA15-3 at this time (P < 0.0001). CA 15-3 was elevated in 69% of the cases of HR+ Her2- primary tumors at time of metastatic relapse. It was elevated in 56% of HR+ Her2+++, 46% of HR- Her2+++ cases and only in 41% of triple-negative cases (P = 0.003). these data confirm that CA 15-3 is very variably elevated at time of metastatic relapse of breast cancer, and this is dependant on HR status.

Lung cancer single intramedullary metastasis vs delayed radionecrosis. A case report.

Intramedullary metastases are rare, accounting for 0.9-5% of spinal metastases. Radiation myelopathy is considered one of the most distressing complications of radiotherapy. In both cases symptoms are aspecific, and there are no characteristic neuroradiologic findings. We describe a case of single intramedullary metastasis from lung microcytoma in a 55-year-old man with a history of malignancy, treated by radiotherapy five years previously. The patient returned to our observation complaining of pain and paraesthesia in the left C7 area. Spinal MRI and rachicentesis findings were aspecific. Ten days later a new MRI showed that the lesion size had increased, and neoplastic cells were found in CSF. Intramedullary metastases are extremely rare, accounting for 0.1-0.4% of all CNS tumors. The risk of developing delayed radionecrosis varies with the total dose administered. In both cases diagnosis is histological, while contrast-enhanced MRI is highly sensitive and specific in identifying and characterizing the lesion. In case of metastatic lesions the prognosis is unfavorable. Differential diagnosis is important because it has a strong effect on patient management.

The Janus face of dendritic cells in cancer.

On the basis of experimental models and some human data, we can assume that tumor outgrowth results from the balance between immunosurveillance (the extrinsic tumor suppressor mechanisms) and immunosubversion dictated by transformed cells and/or the corrupted surrounding microenvironment. Cancer immunosurveillance relies mainly upon conventional lymphocytes exerting either lytic or secretory functions, whereas immunosubversion results from the activity of regulatory T or suppressor myeloid cells and soluble mediators. Although specific tools to target or ablate dendritic cells (DCs) became only recently available, accumulating evidence points to the critical role of the specialized DC system in dictating most of the conventional and regulatory functions of tumor-specific T lymphocytes. Although DC can be harnessed to silence tumor development, tumors in turn can exploit DC to evade immunity. Indeed, DCs harbor defects in their differentiation and stimulatory functions in cancer-bearing hosts and can actively promote T-cell tolerance to self-tumor antigens. In this review, we will focus on the dual role of DC during tumor progression and discuss pharmacoimmunological strategies to harness DC against cancer.

Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer.

BACKGROUND: AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues. PATIENTS AND METHODS: pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials. The distribution of pAKT expression was correlated with HER2 and epidermal growth factor receptor (EGFR) expression. The predictive value of pAKT for the efficacy of adjuvant chemotherapy was determined by test for interaction. RESULTS: pAKT, EGFR, and HER2 were expressed in 119 of 781 (15%), 118 of 758 (16%), and 99 of 775 (13%) assessable tumors. Staining was positive for pAKT in 28 of 99 (28%) and 90 of 676 (13%) HER2+ and HER2- tumors (P < 0.001). pAKT was expressed in 15 of 94 (16%) and 75 of 563 (13%) HER2-/EGFR+ and HER2-/EGFR- tumors, respectively (P = 0.49). A positive staining for pAKT did not correlate with prognosis (P = 0.94), and did not predict the resistance to anthracyclines (test for interaction, P = 0.70). CONCLUSIONS: AKT phosphorylation is associated with HER2 expression but not EGFR expression in patients with early breast cancer. pAKT is not predictive for the efficacy of anthracycline-based adjuvant chemotherapy.

Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer.

BACKGROUND: Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer. PATIENTS AND METHODS: The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors. RESULTS: Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45-2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2-0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors. CONCLUSION: These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.

Breast cancer molecular subclassification and estrogen receptor expression to predict efficacy of adjuvant anthracyclines-based chemotherapy: a biomarker study from two randomized trials.

BACKGROUND: The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy. PATIENTS AND METHODS: Tumor samples from 823 patients included in two randomized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array. Estrogen receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6 expressions were determined by immunohistochemistry (IHC). The potential predictive factors of treatment effect on disease-free survival (DFS) were assessed by interaction tests and multivariate analysis. RESULTS: Sixty-four (8%), 98 (12%), 109 (14%) and 527 (66%) patients presented a Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like breast cancer. ER expression, when assessed by IHC, was an independent predictive factor for the benefit of chemotherapy on DFS (test for interaction, P = 0.0015). The molecular subclassification significantly predicted the efficacy of chemotherapy (test for interaction, P = 0.01), but had no significant added value (P = 0.32) as compared to the ER by treatment interaction. Adjuvant chemotherapy was associated with an adjusted hazard ratio for relapse or death of 0.42 [95% confidence interval (CI): 0.17-1.05], 0.54 (95% CI: 0.27-1.08), 0.35 (95% CI: 0.18-0.68), 1.07 (95% CI: 0.81-1.41) for patients with Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like tumors, respectively. CONCLUSION: The breast cancer molecular subclassification was predictive for chemotherapy efficacy in adjuvant setting, but did not provide significant additional information to ER.