Ectopic sphenoidal ACTH-secreting adenoma revealed by 11C Methionine PET scan: case report.

BACKGROUND: Ectopic ACTH pituitary adenomas (EAPA), located outside the sella turcica and deriving from cellular remnants of Rathke's pouch are a very rare cause of Cushing's syndrome (CS). The diagnosis is often difficult and delayed, even after comprehensive work-up. To our knowledge, we report for the first time an ectopic corticotroph tumor of the posterior wall of the sphenoid sinus, leading to false positive results of bilateral inferior petrosal sinus sampling (BIPPS) and which was finally localized by a co-registered11 C Methionine PET/MR imaging. CASE PRESENTATION: A 48-year-old woman was referred for a high clinical suspicion of ACTH-dependent CS. Biological testing comprising low dose dexamethasone suppression and CRH stimulation tests were indicative of pituitary Cushing's disease, but comprehensive pituitary MRI did not reveal any pituitary adenoma. BIPSS confirmed however a central origin of ACTH secretion (central-to-peripheral ACTH ratio > 100) and revealed a significant right-to-left gradient (6.2), leading to a first right-sided exploratory hypophysectomy, that did not cure the patient. BIPSS images were reviewed and revealed preferential drainage of the left pituitary to the right petrosal sinus, leading us to a left sided exploratory hypophysectomy, which was again unsuccessful. A11 C Methionine PET/MRI was performed and revealed a hypermetabolic lesion adjacent to the posterior wall of the sphenoidal sinus. After surgical resection, this polypoid mass was identified as an ectopic ATCH-secreting pituitary adenoma expressing ACTH and T-Pit and complete remission of hypercortisolism was observed. CONCLUSIONS: In conclusion, we report a case of ACTH-dependent Cushing's syndrome, caused by an ectopic corticotroph adenoma located in the sphenoidal sinus, which perfectly mimicked the biological features of a classical pituitary ACTH adenoma on a comprehensive hormonal evaluation including BIPPS, and the features of a benign naso-sinusal polyp at MRI. We report for the first time a key role of11 C Methionine PET co-registered to high resolution MRI for localizing ectopic adenomas, efficiently guiding surgical removal and leading to complete remission of hypercortisolism.

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

Post-injury smell disorders.

Post-injury smell disorders. PROBLEMS/OBJECTIVES: Head trauma is the third most common aetioiogy of post-traumatic olfactory loss (PTOL). This literature review aims to report the existing knowledge surrounding this issue, exploring the current understanding of the inducing pathogenesis and the assessment and management standards from the early phases to longer-term considerations. METHODOLOGY: Literature search and appraisal in PubMed on the following themes directly associated with PTOL: olfactory disorders, trauma, pathogenesis, examination, recovery and treatment. RESULTS: Scientific evidence was mainly available for epidemiology and exploration tools in cases suffering from PTOL. The current research into obj6ctive batteries of olfactory tests is promising. CONCLUSIONS: This paper highlights the importance of an adequate assessment of PTOL for an early start in olfactory training.

Primary undifferentiated carcinoma of the trachea.

BACKGROUND: Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal localization is exceedingly rare. To the best of our knowledge, only four cases have been reported previously, all in Asian patients. CASE REPORT: A 61-year-old male European patient presented with hemoptysis and cough for several months. The workup revealed a primary tracheal tumor without regional or distant metastasis. The patient was treated with tracheal resection followed by end-to-end reconstruction. Pathologic analysis of the tumor, including immunohistochemistry, confirmed the diagnosis of lymphoepithelioma-like carcinoma. Testing for Epstein-Barr virus by hybridization in situ was massively positive. With a follow-up at 15 months, the patient is alive and free of disease. CONCLUSION: We report the first case of lymphoepithelioma-like carcinoma in the trachea in the European population. Treatment possibilities are discussed. They should be based on each patient's clinical presentation and the results of their preoperative workup.

Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: To investigate the safety and activity of cetuximab in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Cetuximab was administered for 2 weeks before surgery to 33 treatment-naïve patients selected for primary surgical treatment. Tumour biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography ((18)FDG-PET) and imaging were carried out at baseline and before surgery. The primary aim of the study was safety and the secondary aims included metabolical, radiological and pathological tumour response. Five untreated patients were included as controls. RESULTS: Cetuximab given 24 h before surgery was safe. Ninety percent of patients had (18)FDG-PET partial response (EORTC guideline) in the cetuximab group versus 0% in the control group. Delta maximal standardized uptake values (ΔSUVmax) were correlated with tumour cellularity on the surgical specimens (P < 0.0001). For patients with ΔSUVmax less than -25% or less than -50%, Ki67 was significantly decreased by cetuximab (P = 0.01 and 0.003). Cetuximab induced down-regulation of pEGFR (P = 0.0004) and pERK (P = 0.003). CONCLUSIONS: Short-course pre-operative administration of cetuximab is safe and shows a high rate of (18)FDG-PET response. (18)FDG-PET response was correlated with residual tumour cellularity suggesting that (18)FDG-PET deserves further investigation as a potential early marker of cetuximab activity in SCCHN.

Pitfalls in preoperative work-up of parotid gland tumours: 10-year series.

PROBLEMS/OBJECTIVES: Preoperative fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) are the two most widely accepted diagnostic techniques used for the assessment of parotid gland tumours. We retrospectively evaluated the ability of FNAC and MRI to predict malignancy in parotid gland tumours. METHODOLOGY: Over a period of 10 years (2002-2011), parotidectomy for primary parotid gland tumours was performed in a consecutive series of 178 patients. Preoperative MRI was performed in 75% (133/178) of cases, and preoperative FNAC was performed in 70% of cases (124/178). Both modalities were applied in 53% (94/178) of patients. Sensitivity, specificity, and accuracy were analyzed retrospectively for each subgroup of patients. RESULTS: The sensitivity, specificity, and accuracy for predicting malignancy were 45%, 89%, and 84%, respectively, for FNAC (including only diagnostic cytology), and 40%, 88%, and 81%, respectively, for MRI. In the subgroup of patients who underwent both MRI and FNAC, sensitivity, specificity, and accuracy were 50%, 85%, and 80%, respectively. Preoperative MRI values improved significantly after introduction of diffusion-weighted (DW) acquisition in 2007 (71%, 93%, and 91%, respectively). CONCLUSIONS: Compared to previously published results, the high number of nondiagnostic smears and the low sensitivity rates in our series were disappointing, In part, this can be explained by the low percentage of malignant tumours and the high number of low-grade tumours among these. We discuss possibilities for improving preoperative performance, such as ultrasound-guided FNAC.

Preliminary experience of CT imaging of the ischaemic brain penumbra through spectral processing of multiphasic CTA datasets.

To assess ischaemic penumbra through the post-processing of the spectral multiphasic CT Angiography (mCTA) data in acute ischaemic stroke (AIS) patients. Thirty one consecutive patients strongly suspected of severe Middle Cerebral Artery AIS presenting less than 6 h after onset of symptoms or with unknown time of onset of symptoms underwent a standardized CT protocol in spectral mode including Non Contrast CT, mCTA, and Perfusion CT (CTP) on a dual-layer MDCT system. Areas disclosing delayed enhancement on iodine density (ID) maps were highlighted by subtraction of the serial mCTA datasets. Two neuroradiologists independently rated the correspondence between delayed enhancing areas at mCTA and the penumbral/infarcted areas delineated by two validated CTP applications using a 5-levels scoring scale. Interobserver agreement between observers was evaluated by kappa statistics. Dose delivery was recorded for each acquisition. Averaged correspondence score between penumbra delineation using subtracted mCTA-derived ID maps and CTP ones was 2.76 for one application and 2.9 for the other with best interobserver agreement kappa value at 0.59. All 6 stroke mimics out of the 31 patients' cohort were correctly identified. Average dose delivery was 7.55 mSv for the whole procedure of which CTP accounted for 39.7%. Post-processing of spectral mCTA data could allow clinically relevant assessment of the presence or absence of ischaemic penumbra in AIS-suspected patients if results of this proof-of-concept study should be confirmed in larger patients'series.

Percutaneous pedicle screw implantation for refractory low back pain: from manual 2D to fully robotic intraoperative 2D/3D fluoroscopy.

Many surgical treatments for chronic low back pain that is refractory to medical treatments focus on spine stabilization. One of the main surgical procedures consists of placing an interbody cage with bone grafts associated with pedicle screws [2, 25, 30]. This technique can be performed using different approaches: a large open posterior approach, tubular approaches (minimal open) or percutaneously (minimally invasive percutaneous or MIP) [5, 28]. One of the main difficulties is to precisely locate the screws into the pedicle avoiding especially infero-medial pedicle breaches. This difficulty is even great- er when working percutaneously. This paper focuses on percutaneously placed pedicle screws (PPS), reports the use of a robotic multi-axis 2D/3D fluoros- copy to enhance the accuracy of pedicle screw placement and reviews other strategies and results reported in the literature.

Conservative management of complicated Rathke's cleft cyst mimicking pituitary apoplexy.

Summary: Complicated Rathke's cleft cyst (RCC) is a rare occurrence of symptomatic bleeding or growth of a previously asymptomatic (and often undiagnosed) intrasellar cyst derived from remnants of Rathke's pouch, situated on the midline between the adeno- and neurohypophysis. Symptoms may be identical to those of pituitary apoplexy: acute onset of headache, hypopituitarism, and neurological disturbances. Both syndromes may also exhibit a similar appearance of a large haemorrhagic sellar mass at initial radiological evaluation. We report on two patients who presented with headache and complete hypopituitarism. Based on the initial MRI, they were first diagnosed with pituitary apoplexy but managed conservatively with hormone therapy alone because of the absence of severe visual or neurological threat. Upon follow-up at 4 months, clinical evolution was good in both patients but their pituitary mass had not reduced in size and, after careful radiologic reviewing, was more indicative of a large midline complicated RCC. In conclusion, the diagnosis of complicated RCC is challenging because it can mimic pituitary apoplexy clinically, biologically, and radiologically. Clinicians should distinguish between the two entities using specific radiological signs or evolution of the mass at MRI if the patient does not undergo surgery. To our knowledge, we report conservative management of this rare condition for the first time, though it seems appropriate in the absence of neurological compromise or visual compression. Long-term follow-up is however mandatory. Learning points: Complicated Rathke's cleft cyst can mimic pituitary apoplexy, presenting with sudden onset of headache, hypopituitarism, and visual and neurological compromise in the most severe cases. At diagnosis, pituitary MRI may not be able to differentiate between the two entities, showing a large haemorrhagic mass inside the sella, with little or no normal pituitary tissue visible. Patients are often diagnosed with apoplexy at this stage and may undergo pituitary surgery. When surgery has not been performed initially in these patients, repeat imaging at 3-6 months is unchanged and does not show the expected involution usually seen after adenoma apoplexy. Conservative management with hormonal replacement seems a valid option in the absence of visual or neurological deficits that would require trans-sphenoidal surgery.

Holmes tremor in a monocentric series of resected brainstem cavernomas.

OBJECT: Several scientific papers report clinical symptoms, indications, complications and outcomes of brainstem cavernous malformation (BSCM) surgery without reporting on the occurrence of postoperative Holmes tremor (HT). Our purpose is to report our experience with HT in a monocentric series of resected brainstem cavernomas. METHODS: We reviewed all the BSCM surgical records between 2002 and 2018 at Saint-Luc University Hospital's Department of Neurosurgery, Brussels and selected patients developing HT postoperatively. Patients' demographics, symptoms, pre- and postoperative imaging, recurrence and complications were analysed. A PubMed literature review was performed to compare our results with those in the existing literature. RESULTS: In a total series of 18 resected BSCM, 5 patients: 1 male and 4 females, with a median age of 51 years (range 29-59 years), developed HT. The median preoperative mRS score was 2 (range 1-4). GTR was achieved in all patients without surgery-related death. BSCM were located in the mesencephalon in 4 patients (80%) who developed HT. Tremor was noticed between ten days and one year after surgery. One patient saw significant improvements to the point of stopping treatment. The median follow-up period was 2 years (range 1-14 years). At the last follow-up, 40% of our patients showed a worse mRS score, 40% stayed unchanged, and 20% improved. CONCLUSION: We are reporting an original single-center series of patients suffering from HT after BSCM surgery. The risk for HT after surgery is significant for midbrain BSCM. A spontaneous favorable evolution is possible.

Functional Prognostic value of optical coherence tomography in optic chiasmal decompression: A preliminary study.

PURPOSE: To assess the predictive value for functional recovery of Ganglion Cell Complex Layer (GCC) and Retinal Nerve Fiber Layer (RNFL) measurements obtained by Optical Coherence Tomography (OCT) in patients undergoing chiasmal decompression and to define potential OCT thresholds for visual recovery. METHODS: We measured preoperative GCC and RNFL thickness in patients with a sellar and/or perisellar tumor compressing the optic chiasm. Visual recovery was defined as recovery of mean deviation (MD) and pattern standard deviation (PSD) using Humphrey visual field testing after 12 successful decompressions (24 eyes). Receiver operating characteristic curve (ROC) analysis was used to identify the best thresholds. RESULTS: Robust global and focal OCT thresholds were found. Superior GCC≥63µm had the best functional prognostic value (AUC=1) for visual improvement. Mean GCC ≥ 67µm and mean RNFL≥75µm also had excellent predictive values (AUC>0.9). CONCLUSION: In this preliminary study, significant preoperative OCT thresholds for early visual recovery after chiasmal decompression were identified, mainly regarding GCC measurements. Further studies on larger cohorts with closely scheduled follow-up could refine our results.

Olfactory bulb volume and depth of olfactory sulcus in patients with idiopathic olfactory loss.

Olfactory loss is considered as idiopathic (IOL) when no cause can be found, neither on the basis of a standardized history nor a thorough clinical evaluation. Olfactory bulb volume (OB) has been shown to be decreased in patients with olfactory loss due to trauma, infections, or sinonasal disease. However, OB volume has not yet been investigated in IOL patients. Twenty-two patients with IOL were compared with 22 controls in terms of olfactory performance and of OB volume assessed with magnetic resonance imaging (MRI). Psychophysical testing confirmed that patients had lower scores than controls: P < 0.001 for threshold (T), discrimination (D), identification (I) and global TDI score. Mean right, left and total OB volumes were significantly smaller for IOL patients as compared to controls. Both for IOL and controls, there was a significant correlation between odor thresholds and total OB volume, respectively. In conclusion, patients with IOL have decreased olfactory function and decreased OB volume when compared with controls. This was previously demonstrated for patients with postinfectious or posttraumatic olfactory dysfunction, but not for patients with uneventful conditions possibly damaging their olfactory apparatus.

[Intramedullary tumours and pseudotumours]. / Moelle épinière tumorale et pseudo-tumorale.

Swelling of the spinal cord and/or enhancement after intravenous gadolinium administration are not always specific features of intramedullary tumour. These may also be seen in association with several diseases of inflammatory, infectious, granulomatous or vascular origin. A tumour is characterized by its sagittal location, axial topography: central, lateral or exophytic, its size and size of the spinal canal, macroscopic components: calcium, fat, methemoglobin, melanin, hemosiderin, vascular pedicle, cystic component, enhancement after intravenous gadolinium administration, effect on the spinal cord tracts and edema. Characteristics: astrocytoma is lateral and infiltrative, ependymoma is central with white matter tract displacement and hemosiderin cap, hemangioblastoma is postero-lateral and shows enhancement with a vascular pedicle, metastases are very edematous or leptomeningeal in location.

Intracranial brain parenchymal spread of mucormycosis through olfactory tract: a diffusion-weighted imaging-based concept.

Mucormycosis is an opportunistic fungal infection involving among others the paranasal sinuses, nasal fossa and brain parenchyma. Mucor can invade the brain parenchyma by either contiguous spread from the paranasal sinuses or through vascular invasion. We report a case of fatal rhino-cerebral mucormycosis in whom cytotoxic edema at magnetic resonance diffusion-weighted imaging was symmetrically restricted to both neocortical and paleocortical primary areas of olfactory projection at earliest phase of the disease process. Shortly later tissue damage extended into the whole brain. This undescribed observation raised the hypothesis of preferential way of brain invasion by Mucor through the olfactory tract.

Diagnostic and therapeutic pitfalls in neurosarcoidosis.

Neurosarcoidosis is a diagnostic challenge, especially in the absence of systemic involvement, even when cerebral biopsies show noncaseating granulomas. We report a patient with a pineal germinoma associated with a extensive peri- and intra- tumoural granulomatous reaction, who was first diagnosed as possible neurosarcoïdosis. A second patient was initially considered as suffering from Multiple Sclerosis. Brain biopsy showed typical granulomas and gallium scintigraphy revealed other locations of the disease. Unfortunately, he developed a severe, steroid-induced, epidural lipomatosis at the Th3-Th8 levels and died unexpectedly after surgical decompression. Granulomatous inflammation in a tissue obtained by biopsy from a midline lesion should be always considered for the differential diagnosis of germinoma. Corticosteroid-sparing immunosuppressant drugs should be used early in neurosarcoïdosis.

Olfactory bulb volume in the clinical assessment of olfactory dysfunction.

The olfactory bulb collects the sensory afferents of the olfactory receptor cells located in the olfactory neuroepithelium. The olfactory bulb ends with the olfactory tract and is closely related to the olfactory sulcus of the frontal lobe. Many studies demonstrated that olfactory bulb volume assessed with magnetic resonance imaging is related to the olfactory function both in normal and pathological conditions. It has been shown that olfactory bulb volume changes with the degree of olfactory dysfunction, that it decreases with the duration of the olfactory loss and that patients with qualitative disorder such as parosmia have smaller olfactory bulbs than patients without parosmia. In this review, we will discuss the actual knowledge regarding olfactory bulb function, practical ways to measure olfactory bulb volume and olfactory sulcus depth, and report systematic observations regarding these measurements related to various causes of olfactory dysfunction, e.g. infection of the upper respiratory tract, head trauma, or neurodegenerative disease. Measurement of olfactory bulb volume may provide valuable information for patients with olfactory dysfunction.

How to measure olfactory bulb volume and olfactory sulcus depth?

In combination with psychophysical testing and electrophysiological studies, magnetic resonance imaging plays a role in the clinical evaluation of patients with an olfactory dysfunction. Quantitative measurements of olfactory bulb volume and of olfactory sulcus depth, and the morphological depiction of structural abnormalities, make synergistic contributions to the accurate radiological diagnosis of smell dysfunction. Moreover, the plasticity of our olfactory system can be demonstrated by temporal changes in OB volumetric measurements. In this paper, we provide an outline of how to measure olfactory bulb volume and olfactory sulcus depth, with numerous illustrative cases of patients with congenital anosmia, post-infectious or posttraumatic olfactory loss and sinonasal-related olfactory dysfunction.

T2-weighted magnetic resonance imaging characterization of prolactinomas and association with their response to dopamine agonists.

PURPOSE: Recent work supports the use of T2-weighted MRI intensity as a tool for treatment stratification in acromegaly. Our study aimed to establish if the pattern of T2 intensity could be a predictor of hormonal and/or tumoral response to dopamine agonists (DAs) in prolactinomas. METHODS: This was a retrospective study performed in two academic centers. We characterized the magnetic resonance T2-weighted aspect of prolactinomas (signal intensity and homogeneity in the whole tumors) before DA therapy and correlated this pattern to the prolactin (PRL) concentration at diagnosis and to hormonal and tumoral responses after 1 year of medical treatment. We separately analyzed a subgroup of prolactinomas visually very bright in more than 50% of the surface ("cystic" tumors). RESULTS: Out of 70 prolactinomas, 80% were T2 hyperintense and 40% were heterogeneous. At diagnosis, heterogeneous prolactinomas were more frequent in men (68% vs. 28.9%, p ≤ 0.011), larger (median area 304.5 mm2 vs. 56.5 mm2, p ≤ 0.021), taller (mean height 18.6 mm vs. 9.9 mm, p < 0.001), more secreting (median PRL ULN_area 23 µg/L/cm2 vs. 12.6 µg/L/cm2, p ≤ 0.032) and had poorer hormonal response to DA as compared with homogeneous prolactinomas. "Cystic" tumors were diagnosed almost exclusively in women and secreted less prolactin, but showed similar hormonal and tumoral response as "non-cystic" tumors. In homogeneous prolactinomas, the T2-weighted intensity ratio was correlated to prolactin secretion, although not significantly, and did not predict hormonal and tumoral response to DA. CONCLUSIONS: Our study confirms that hypo/isointense prolactinoma is a rare finding and suggests for the first time that the heterogeneity of prolactinoma T2 signal at diagnosis might be correlated with a different clinical behavior and could be used as a negative predictor factor of hormonal response to DA.

Acute ischaemic pontine stroke revealing lyme neuroborreliosis in a young adult.

We report the case of a 23-year-old male patient who suddenly developed right hemiparesis, cerebellar ataxia, dysarthria, and bilateral dysmetria. Brain magnetic resonance (MR) examination demonstrated hyperacute ischaemic lesions within the pons. CSF analysis revealed a high protein content, lymphocytic pleocytosis, and oligoclonal IgG bands not present in the serum. Elevated IgM and IgG anti-Borrelia burgdorferi antibodies were shown in both serum and CSF samples, associated with an intrathecal synthesis of these antibodies. Ischaemic CNS lesions have been rarely observed as the first manifestation of Lyme neuroborreliosis. The putative mechanism for parenchymal ischaemia is the local extension of inflammatory changes from meninges to the wall of penetrating arterioles.