Prolonged Response Induced by Single Agent Vemurafenib in a BRAF V600E Spinal Ganglioglioma: A Case Report and Review of the Literature.

Spinal ganglioglioma is a rare low-grade, slow-growing tumor of the central nervous system affecting mostly children and young adults. After surgery, some patients show tumor recurrence and/or malignant transformation. Gangliogliomas harbor molecular deficiencies such as mutations in the B-rapidly accelerated fibrosarcoma (BRAF) gene, resulting in activation of a downstream signaling pathway and cancer development. Vemurafenib is a BRAF inhibitor used to treat patients with BRAF V600E-mutated cancer. Although a few studies have reported the clinical responses in gangliogliomas, the sequence and duration of treatment have not been established. We describe a case of an adult with a progressive BRAF V600E mutant spinal cord ganglioglioma 9 years after surgery who was treated with vemurafenib. This treatment resulted in a partial response within 2 months, which was sustained for more than a year. The patient then decided to stop treatment because of side effects. Despite this decision, the tumor showed no sign of progression 21 months after treatment discontinuation. This is the first reported case of a response to vemurafenib in an adult with progressive spinal cord BRAF V600E-mutated ganglioglioma which was sustained after treatment discontinuation.

Long-term adverse event: inflammatory orbitopathy induced by pembrolizumab in a patient with metastatic melanoma.

The recent advent of immune checkpoint inhibitors (ICI), including anti-programmed cell death 1 protein (anti-PD-1) agents has revolutionized the therapeutic approach of metastatic malignancies. Yet, ICI can disrupt immune tolerance resulting in enhanced immune activation in normal tissues with significant toxicity. A dysregulated activation of T-cells directed to normal tissues stands as the main mechanism of immune-related adverse events (irAE). To date, only two cases of immune-related inflammatory orbitopathy related to anti-PD-1 agents have been reported. This rare immune adverse event usually occurred early after ICI initiation. Here, we report the first case of late inflammatory orbitopathy occurring in a melanoma patient treated with pembrolizumab. Consequently, the occurrence of irAE under ICI should be monitored, even late after treatment instauration.

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy.

INTRODUCTION: Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS: This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m(2) per day, followed by six cycles of maintenance temozolomide (150-200 mg/m(2), five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS: One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5-15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3-4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS: This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3-4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients.

Intensity of prolactinoma on T2-weighted magnetic resonance imaging: towards another gender difference.

INTRODUCTION: Clinical presentations of prolactinomas are quite different between genders. In comparison with women's prolactinoma, those in men showed predominance of large tumors with high prolactin (PRL) levels. This preponderance could be attributed to a greater proliferative potential of the tumors. Differences in magnetic resonance imaging (MRI) signal at diagnosis have not been yet clearly evaluated. METHODS: We conduct a retrospective study comparing MRI signal intensity (SI) on T2-weighted images (T2-WI) between 41 men and 41 women to investigate whether or not men prolactinoma present specific features. RESULTS: In addition to the size of the adenoma and PRL levels (P < 0001), prolactinomas in men also exhibit differences from those in women in signal on T2-WI on MRI (P < 0001). Women's prolactinomas are mostly of high SI on T2-WI while men's prolactinomas exhibit a more heterogeneous pattern of SI on T2-WI. Prolactinomas presenting with low SI on T2-WI are almost exclusively encountered in men. CONCLUSIONS: Presence of T2-WI hypointensities in pituitary adenoma can be predictive of a different subtype of prolactinoma almost encountered in men and possibly translate the presence of spherical amyloid deposits, in agreement with the literature.

[Cerebellar gangliocytoma in an 11-year-old child]. / Gangliocytome du cervelet chez un enfant de 11ans.

Cerebellar gangliocytoma can correspond to Lhermitte-Duclos disease, a benign hamartomatous malformation encountered in young adults. It can also be a part of gangliogliomas/gangliocytomas family, which usually encompasses temporal pediatric neoplasms associated with longstanding seizures. We report a case of a young 11-year-old patient who presented with a gangliocytoma of the cerebellum revealed by neurologic manifestations (headache, dyspraxia, equilibrium and gait disturbances). Diagnosis was made on surgical material. Tumour was characterized by dysplastic mature ganglion cells, perivascular lymphocytic infiltrates and no glial neoplastic component. By immunohistochemistry, ganglion cells expressed neurofilaments, MAP2 protein, synaptophysin, chromogranin A and S100 protein. BRAF V600E mutation was absent. Clinical characteristics, radiology, histopathology of the two main diagnoses are discussed.

Transfontanellar contrast enhanced ultrasound in infants: initial experience.

BACKGROUND AND PURPOSE: Transfontanellar contrast enhanced ultrasound (TCEUS) in infants with neurological diseases has not been previously reported. Thus, the objective of our study was to describe the imaging findings of transfontanellar contrast enhanced ultrasound (TCEUS) performed in various neurological conditions in infants and to compare the findings with non-enhanced transfontanellar ultrasound (TFUS) and MRI. METHODS: Local institutional review board approval was obtained and, because of the need to catheterize children for contrast media administration, written informed consent of parents was obtained prior to all performed TCEUS. Twelve infants who underwent 12 TCEUS were included in this study from June 2009 to June 2012. Second generation contrast material was used (Bracco). TCEUS imaging findings were compared with those of conventional transfontanellar ultrasound in each case and with MRI. RESULTS: In 10 out of the 12 performed examinations, TCEUS showed abnormalities which were not depicted on non-enhanced TFUS. Accurate diagnosis of TCEUS compared with MRI was found in 10 out of 12 initial TCEUS. No adverse events during or immediately after contrast media injection occurred. CONCLUSION: TCEUS appears to be a potential bedside accessible non-ionizing alternative imaging modality in the assessment of neonatal brain injury. It provides additional information when compared to non-enhanced transfontanellar US, especially in the field of brain perfusion assessment. Moreover, the information provided seems to be accurate when compared with those of MRI.

Fractional anisotropy in three variants of primary progressive aphasia.

OBJECTIVE: Our aim was to report diffusion tensor imaging (DTI) patterns in three patients, each with a different primary progressive aphasia (PPA) variant. DESIGN: One agrammatic PPA, one semantic PPA, and one logopenic PPA subject underwent a magnetic resonance imaging examination including DTI sequences. The fractional anisotropy (FA) value was calculated in regions of interest (ROIs) involved in these three variants (perisylvian region, temporal pole, and parietotemporal junction) for each patient. Left-right FA ratios in each ROI were compared between PPA subjects and a group of three amnestic mild cognitive impairment patients with a cerebrospinal fluid biomarker profile of the Alzheimer type. RESULTS: The FA values were lower in the left hemisphere (p=0.03). The lowest FA values were observed in the left perisylvian region for the non-fluent/agrammatic subtype PPA patient, in the left anterior temporal lobe for the semantic subtype PPA patient, and in the left parietotemporal junction for the logopenic patient (p=0.028). The left-right FA ratio in these specific ROIs for each PPA variant was significantly lower than in the amnestic mild cognitive impairment group (p=0.009). CONCLUSION: DTI patterns could be an effective new tool for diagnosing PPA and classifying the three variants.

[Imaging of pituitary adenomas]. / Imagerie des adénomes hypophysaires.

In cases of pituitary hormone hypersecretion, magnetic resonance imaging (MRI) can demonstrate the causal lesion, which is often small (microadenoma). In pituitary adenomas with suprasellar extension, MRI shows the tumor's relation to the surrounding structures: the optic chiasm, the internal carotid artery, the sphenoidal sinus, etc. MRI usually makes it possible confirm or rule out any cavernous sinus invasion by the pituitary adenoma, a determination essential for planning treatment. After pituitary surgery, MR imaging is again essential for visualizing any residual tumor tissue and - if the MRI is carefully performed to be reproducible - for assessing its development over time.

Assessment of the course and division patterns of the middle cerebral artery M1 segment. Transcranial power doppler compared with 3D time-of-flight magnetic resonance angiography at 3 T.

BACKGROUND AND PURPOSE: The present study was undertaken to assess the ability of bedside transcranial color-coded sonography (TCCS) to define the course and the patterns of the division of the middle cerebral artery (MCA) M1 segment compared with 3D time-of-flight magnetic resonance angiography (MRA) at 3 T. METHODS: Because MRA is considered as a reliable noninvasive technique to depict the normal anatomy of the intracranial artery, we prospectively defined the course and the patterns of division of 100 MCA M1 segments using bedside TCCS and compared the results with MRA findings. RESULTS: In 68/85 cases (80%), the sonographer was able to define the division of the M1 segment, and classified these as bipode for 50/68 (73.5%), monopode for 16/68 (23.5%) and tripode for 2/68 (3%). A comparison of the TCCS and MRA findings showed a perfect correlation (100%) for the course of the M1 segment. As for the type of division, the correlation was good in 45/68 of cases (67%). TCCS had a sensitivity of 78%, a specificity of 67%, a positive predictive value of 87% and a negative predictive value of 52%, when used to determine whether the division was bipode or not. CONCLUSIONS: Our results show that bedside TCCS can now provide anatomical information on the M1 segment of the MCA.

Main anatomical features of the M1 segment of the middle cerebral artery: a 3D time-of-flight magnetic resonance angiography at 3 T study.

The purpose of our study was to determine the main anatomical features of the M1 segment of middle cerebral artery (MRA) using a 3D TOF-MRA at 3 T. Reconstructed and post-processed MRA images were independently analysed by two anatomists in order to determine the course patterns, the division patterns and the early cortical branches patterns of the M1 segments. The division patterns were defined as bipode, tripode or other. The ECB were studied according to their number and their distance from the origin of the M1 segment. The interobserver agreement, to determine the division patterns of the M1 segment, was calculated. The division of the M1 segment was bipode in 73% of the MCAs, monopode in 17%, tripode in 9%, and fan-shaped in 1. In 46% of the cases no ECB was found. In the other cases, only 1 ECB was found and it arose from the medium part of the M1 segment. Our results confirm post-mortem microdissection studies and show that strict anatomical criteria may be applied to 3D TOF MRA at 3 T.

T1 signal hyperintensity in the sellar region: spectrum of findings.

T1 signal hyperintensity is a common finding at magnetic resonance imaging of the sellar region. However, this signal intensity pattern has different sources, and its significance depends on the clinical context. Normal variations in sellar T1 signal hyperintensity are related to vasopressin storage in the neurohypophysis, the presence of bone marrow in normal and variant anatomic structures, hyperactive hormone secretion in the anterior pituitary lobe (eg, in newborns and pregnant or lactating women), and flow artifacts and magnetic susceptibility effects. Pathologic variations in T1 signal hyperintensity may be related to clotting of blood (in hemorrhagic pituitary adenoma, pituitary apoplexy, Sheehan syndrome, or thrombosed aneurysm) or the presence of a high concentration of protein (Rathke cleft cyst, craniopharyngioma, or mucocele), fat (lipoma, dermoid cyst, lipomatous meningioma), calcification (craniopharyngioma, chondroma, chordoma), or a paramagnetic substance (manganese, melanin). After treatment, T1 signal hyperintensity may result from the presence of materials used for surgical packing (gelatin sponge, fat); from compression of the cavernous sinus and reduction of the venous flow, caused by overpacking of the operative bed; or from hormone hypersecretion by a remnant of normal tissue in the anterior lobe of the pituitary gland.

Magnetic resonance imaging of pituitary adenomas.

Today, MR is the only method needed for the morphological investigation of endocrine-active pituitary adenomas. In acromegaly and Cushing's syndrome, the therapeutic attitude is directly dictated by MR data. We present the MR aspect of pituitary adenomas according to size, sex, age, endocrine activity and a few particular conditions such as hemorrhagic pituitary adenomas, pituitary adenomas during pregnancy, cavernous sinus invasion and postsurgical changes. When an intrasellar mass extending out of the sella turcica is detected, the goal of the MR examination is to indicate precisely the origin of the tumor, its extension in relation to the various surrounding structures, its structure and its enhancement in order to help in the differential diagnosis. Demonstration of very small pituitary adenomas remains a challenge. When SE T1- and Turbo SE T2-weighted sequences are non-diagnostic, enhanced imaging becomes mandatory; half-dose gadolinium injection, delayed sequence, dynamic imaging can be of some help.

Preoperative location of the pituitary bright spot in patients with pituitary macroadenomas.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the location of the pituitary bright spot in patients with pituitary macroadenomas before surgery. METHODS: A total of 54 patients with pituitary macroadenomas were retrospectively included in this study. Nonenhanced spin-echo T1-weighted MR images were reviewed to identify the location of the high-intensity-signal posterior pituitary lobe that indicates antidiuretic hormone (ADH) storage. Images were acquired with a 1.5-T machine by using 3-mm-thick contiguous sections in two or three orthogonal planes and a 300 x 512 matrix. RESULTS: The bright spot corresponding to ADH storage was identified in 44 (81%) patients. Two groups of patients were defined by the height of the macroadenoma: Group A patients (n = 27) had pituitary macroadenomas less than 20 mm in height, and group B (n = 27) had macroadenomas 20 mm or larger. In group A, the bright spot was identified in 25 patients (93%); it was located in the sella in 24 of these cases (96%). In group B, the bright spot was identified in 19 patients (70%); it was in an ectopic location in 14 of these cases (74%). CONCLUSION: MR imaging can be used to depict the pituitary bright spot in most patients with pituitary macroadenomas before surgery. The bright spot is usually identified at its expected location within the sella in patients with pituitary macroadenomas less than 20 mm in height, whereas an ectopic location is common when pituitary macroadenomas are larger more than 20 mm.