Efficacy of endoscopic endonasal transsphenoidal surgery for Cushing's disease in 230 patients with positive and negative MRI.

OBJECT: The primary objective was to assess the remission rate, and the secondary objectives were to evaluate the early complications and recurrence rate and to define the predictive factors for the remission and recurrence rates. PATIENTS AND METHODS: This prospective single-center study included 230 consecutive patients, operated on by a single surgeon for Cushing's disease via a transsphenoidal endoscopic endonasal approach, over a 6-year period (2008-2013). The patients included in this series were all adults (>18 years of age), who presented with clinical and biological characteristics of Cushing's disease confirmed based on dedicated MRI pituitary imaging. Biochemical remission was defined as a postoperative serum cortisol level <5 µg/dl on the 2nd day following surgery that required glucocorticoid replacement therapy. RESULTS: The remission rate for the global population (n = 230) with a follow-up of 21 ± 19.2 months concerned 182 patients (79.1%) divided into 132 patients (82.5%) with positive MRI and 50 patients (71.4%) with negative MRI with no statistically significant difference (p = 0.077). Complications occurred in 77 patients with no deaths. A total of 22% of patients had transient diabetes insipidus and 6.4% long-term diabetes insipidus, and no postoperatively CSF leakage was observed. The recurrence rate was 9.8% with a mean time of 32.7 ± 15.2 months. The predictive factors for the remission rate were the presence of pituitary microadenoma and a positive histology. No risk factors were involved regarding the recurrence rate. CONCLUSION: Whatever the MRI results, the transsphenoidal endonasal endoscopic approach remains the gold standard treatment for Cushing's disease. It was maximally effective with a remission rate of 79.1% and lower morbidity.

Silent, but not unseen: multimicrocystic aspect on T2-weighted MRI in silent corticotroph adenomas.

OBJECTIVE: Silent corticotroph adenomas (SCAs) present as nonfunctional pituitary tumours in routine pre-operative evaluation. The objective of this study was to evaluate the diagnostic accuracy of MRI T2-weighted sequences for detecting the corticotroph subtype pre-operatively. DESIGN: The pre-operative T2-weighted MRI sequences were retrospectively evaluated in patients with SCA and two control groups: clinically manifest corticotroph macroadenomas (CSMs) and nonfunctional gonadotroph macroadenomas (NFGMs). All were selected from a registry of 1096 patients in whom transsphenoidal surgery was performed in the same tertiary reference centre. T2-weighted MRI sequences were independently classified by one senior endocrinologist and one senior radiologist who were blinded to the clinical and histological features. PATIENTS: Seventeen patients with SCA, 14 with CSM and 60 with NFGM were included in this study. MEASUREMENTS: Pituitary MRI with T2-weighted sequences. Two aspects were retained: multiple microcysts (MMs) and the absence of microcysts. Hormonal data included plasma prolactin, IGF-1, testosterone or oestradiol, LH, FT4, TSH, morning plasma cortisol and an ACTH-stimulation test, when available. RESULTS: Multiple microcysts were present in 76% (13/17) of SCAs, 21% (3/14) of CSMs and 5% (3/60) of NFGMs. The presence of MMs in clinically nonfunctioning macroadenomas had a sensitivity of 76% and a specificity of 95% for predicting SCA. CONCLUSION: The presence of MMs in T2-weighted MRI is a good diagnostic tool to suggest the corticotroph subtype in an apparently nonfunctional pituitary tumour.

MRI and MRA of spinal cord arteriovenous shunts.

The purpose of this review is to describe the diagnostic criteria for spinal cord arteriovenous shunts (SCAVSs) when using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and to discuss the extent to which the different MRI and MRA sequences and technical parameters provide the information that is required to diagnose these lesions properly. SCAVSs are divided into four groups according to location (paraspinal, epidural, dural, or intradural) and type (fistula or nidus); each type of lesion is described. SCAVSs are responsible for neurological symptoms due to spinal cord or nerve root involvement. MRI is usually the first examination performed when a spinal cord lesion is suspected. Recognition of the image characteristics of vascular lesions is mandatory if useful sequences are to be performed-especially MRA sequences. Because the treatment of SCAVSs relies mainly on endovascular therapies, MRI and MRA help with the planning of the angiographic procedure. We explain the choice of MRA sequences and parameters, the advantages and pitfalls to be aware of in order to obtain the best visualization, and the analysis of each lesion.

A case of spontaneous brain arteriovenous malformation occlusion: Imaging analysis and clinical debate.

The spontaneous occlusion of brain arteriovenous malformations (bAVMs) is a rare event, particularly for unruptured ones. Associated factors include single-venous drainage and small nidus size. Most of the previously reported cases were ruptured bAVMs. We report the case of a middle-aged male patient with an unruptured, rolandic, left-sided bAVM associated with a 30-year history of refractory epilepsy. We documented the spontaneous thrombosis of the venous drainage of the AVM without any sign of bleeding. Finally, we underline the difference between ruptured-induced occlusion and truly spontaneous thrombosis of the bAVMs.

Diagnosis and management of children and adult craniopharyngiomas: a French Endocrine Society/French Society for Paediatric Endocrinology & Diabetes Consensus Statement.

Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up.

Follow-up of coiled intracranial aneurysms: comparison of 3D time-of-flight and contrast-enhanced magnetic resonance angiography at 3T in a large, prospective series.

OBJECTIVES: To compare 3D-TOF magnetic resonance angiography (MRA) and contrast-enhanced MRA (CE-MRA) sequences at 3T in the follow-up of coiled aneurysms with digital subtracted angiography (DSA) as the gold standard. METHODS: DSA, 3D-TOF and CE-MRA were performed in a prospective series of 126 aneurysms in 96 patients (57 female, 39 male; age: 25-75 years, mean: 51.3 ± 11.3 years). The quality of aneurysm occlusion was assessed independently and anonymously by a core laboratory. RESULTS: Using DSA (gold standard technique), total occlusion was depicted in 57 aneurysms (45.2%), neck remnant in 34 aneurysms (27.0%) and aneurysm remnant in 35 aneurysms (27.8%). Sensitivity, specificity, positive predictive value and negative predictive value were very similar with 3D-TOF and CE-MRA. Visibility of coils was much better with 3D-TOF (95.2%) than with CE-MRA (23.0%) (P < 0.001). Also, substantial artefacts were less frequent with 3D-TOF (4.0%) than with CE-MRA (11.9%; P = 0.012). CONCLUSIONS: In this large prospective series of patients with coiled aneurysms, at 3T 3D-TOF MRA was equivalent to CE-MRA for the evaluation of aneurysm occlusion, but coil visibility was superior at 3D-TOF. Thus the use of 3D-TOF at 3T is recommended for the follow-up of coiled intracranial aneurysms. KEY POINTS: • Different Magnetic Resonance (MR) imaging techniques are used to evaluate intracranial aneurysms. • At 3T MR, 3D-TOF and CE-MRA appear equivalent for evaluating coiled aneurysms.. • Coils are better visualised on 3D-TOF than on CE-MRA. • Combined analysis of 3D-TOF and CE-MRA does not seem helpful. • At 3T, 3D-TOF techniques are recommended for monitoring patients with coiled aneurysms.

Developmental venous anomalies with capillary stain: a subgroup of symptomatic DVAs?

INTRODUCTION: Intracranial developmental venous anomalies (DVAs) are considered benign vascular dispositions; they are asymptomatic in the vast majority of cases. They represent extreme variations of the venous drainage and may rarely be responsible for focal venous ischemia leading to neurological dysfunction. The aim of the study is to analyze a group of patients with symptomatic DVAs with capillary stain at angiography. METHODS: We retrospectively reviewed the clinical and radiological features of patients in which a DVA was considered the cause of a neurological event. In all the patients, the DVA was suspected by angio-CT or MRI and conventional angiography was performed to detail the angioarchitecture of the DVA. RESULTS: A total of 7 patients and 11 DVAs were identified; three patients had multiple DVAs. Three DVAs were frontal, two were parietal, two were thalamic, one was in the midbrain, and three were cerebellar. Patients presented with progressive neurological deficits, seizures, or cerebral hemorrhage. All these DVAs were associated with a peculiar capillary stain at angiography. CONCLUSION: Although being normal anatomical variations, DVAs may create, because of hemodynamic unbalance, venous ischemia that induces angiogenic phenomena. MRI shows the suffering of the brain and angiography witnesses this angiogenesis under the form of capillary stain. Conventional angiography can thus provide useful information to recognize "atypical" symptomatic DVAs.

Consensus statement by the French Society of Endocrinology (SFE) and French Society of Pediatric Endocrinology & Diabetology (SFEDP) on diagnosis of Cushing's syndrome.

Cushing's syndrome is defined by prolonged exposure to glucocorticoids, leading to excess morbidity and mortality. Diagnosis of this rare pathology is difficult due to the low specificity of the clinical signs, the variable severity of the clinical presentation, and the difficulties of interpretation associated with the diagnostic methods. The present consensus paper by 38 experts of the French Society of Endocrinology and the French Society of Pediatric Endocrinology and Diabetology aimed firstly to detail the circumstances suggesting diagnosis and the biologic diagnosis tools and their interpretation for positive diagnosis and for etiologic diagnosis according to ACTH-independent and -dependent mechanisms. Secondly, situations making diagnosis complex (pregnancy, intense hypercortisolism, fluctuating Cushing's syndrome, pediatric forms and genetically determined forms) were detailed. Lastly, methods of surveillance and diagnosis of recurrence were dealt with in the final section.

Controlateral cavernous syndrome, brainstem congestion and posterior fossa venous thrombosis with cerebellar hematoma related to a ruptured intracavernous carotid artery aneurysm.

Intracavernous carotid artery aneurysms (ICCAs) are rarely associated with life-threatening complications. We describe a 55-year-old woman who, after the rupture of an intracavernous carotid artery aneurysm, presented with a contralateral cavernous sinus syndrome and severe posterior fossa and spinal cord symptoms. Following parent artery occlusion, thrombosis of the posterior fossa and spinal cord veins caused a progressive worsening of the neurological status to a "locked-in" state. The patient fully recovered with anticoagulation therapy. Comprehension of the pathophysiological mechanism associated with the rupture of ICCA and early diagnosis of the related symptoms are essential in order to plan a correct treatment that includes the management of the aneurysm rupture and of possible complications related to venous thrombosis.

Intradural spinal cord arteriovenous shunts in a personal series of 210 patients: novel classification with emphasis on anatomical disposition and angioarchitectonic distribution, related to spinal cord histogenetic units.

OBJECTIVE: Few classifications of intradural spinal arteriovenous shunts (ID-SAVSs) have considered their anatomical localization in relation to their phenotype and angioarchitectonics. The authors propose another vision of ID-SAVSs allowing a reappraised classification based on analysis of the anatomical disposition, angioarchitecture, and histogenetic location of these vascular malformations. METHODS: The radiological and clinical records of 210 patients with ID-SAVSs were retrospectively reviewed, considering their localization, vascular architectonics, and correlation with the 5 histogenetic units of the spinal cord. Among these, 183 files with complete data allowed precise analysis of the ID-SAVSs. RESULTS: Among these 183 files (162 and 21 cases with single and multiple lesions, respectively), different entities were identified: 13 pial macro arteriovenous fistulas (MAVFs), 92 pial micro arteriovenous fistulas (mAVFs), 33 superficial pial niduses, and 69 intramedullary niduses. Thirteen sulcal shunts (either fistulas or niduses) were considered subtypes of pial lesions. Among the 21 multiple cases, 11 were monomyelomeric while 10 were multimyelomeric. Pial lesions, either fistulas or niduses, were dominantly vascularized by pial arteries (anterior or posterior depending on the localization of the shunt) and occasionally (except for MAVFs) by transmedullary arteries. Pial niduses occasionally extended into the funiculus by recruiting intrinsic veins or by extension of the nidus itself inside the white matter. Intramedullary niduses were always vascularized by both centrifugal and centripetal feeders, respectively, from sulcal arteries (SAs) and pial arteries. Sulcal lesions are pial lesions located within the ventral median sulcus and vascularized by SAs and veins. Single or multiple ID-SAVSs can be part of various syndromes such as hereditary hemorrhagic telangiectasia, Parkes-Weber, RASA1, CLOVES, and spinal arteriovenous metameric syndromes. Histogenetic analyses revealed a specific distribution of each ID-SAVS in the 5 histogenetic units of the spinal cord: intramedullary niduses were found almost equally from cervical to thoracic units, while MAVFs and mAVFs were mostly found from thoracic to postcrural ones. Pial niduses showed intermediate features between intramedullary and fistulous lesions and were mostly distributed from brachial to crural segments. CONCLUSIONS: Precise analysis of the anatomical disposition of ID-SAVSs in relation to functional histogenetic units allows a better understanding of these lesions and improved therapeutic management.

Partially thrombosed intracranial aneurysms: symptoms, evolution, and therapeutic management.

BACKGROUND: Partially thrombosed intracranial aneurysms (PTIAs) are different from saccular or nonthrombosed giant or large aneurysms, as they are characterized by multiple intramural thrombotic phenomena related to recurrent vessel wall dissections. METHODS: We retrospectively reviewed clinical and radiological files of 23 consecutive patients with PTIAs (mean age 49.3 years). Twenty-two lesions were studied by magnetic resonance imaging (MRI). Patients were managed by endovascular treatments, medically with steroids, or conservatively. RESULTS: Thirteen patients presented with progressive neurological symptoms. Subarachnoid hemorrhage was suspected but not proven in three. At MRI, 90.9% of PTIAs caused mass effect; perilesional T2 hypersignal compatible with edema was evident in 13.6%. Aneurysmal wall enhancement was detectable in 63.2% of the PTIAs and considered a marker of inflammatory processes. Parent artery occlusion was performed in seven patients with clinical improvement in six. Selective coiling was proposed in three patients (one improved, one remained stable, and one experienced symptoms progression). Three patients were treated with steroids and improved. Ten patients were managed conservatively: eight because spontaneous thrombosis of the lesion had been diagnosed and two because of clinical and radiological stability. CONCLUSIONS: The natural history of PTIAs is different from other aneurysms. They most commonly present with progressive neurological symptoms due to mass effect. MRI properly diagnoses PTIAs and allows precise follow-up, more accurately than angiography because it detects prominent "abluminal" features indicating inflammation and neovascularization. Spontaneous thrombosis is part of the natural history of PTIAs and it should be taken in consideration when discussing the therapeutic management.

Pangenomic Classification of Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) are common, with five main histological subtypes: lactotroph, somatotroph, and thyrotroph (POU1F1/PIT1 lineage); corticotroph (TBX19/TPIT lineage); and gonadotroph (NR5A1/SF1 lineage). We report a comprehensive pangenomic classification of PitNETs. PitNETs from POU1F1/PIT1 lineage showed an epigenetic signature of diffuse DNA hypomethylation, with transposable elements expression and chromosomal instability (except for GNAS-mutated somatotrophs). In TPIT lineage, corticotrophs were divided into three classes: the USP8-mutated with overt secretion, the USP8-wild-type with increased invasiveness and increased epithelial-mesenchymal transition, and the large silent tumors with gonadotroph transdifferentiation. Unexpected expression of gonadotroph markers was also found in GNAS-wild-type somatotrophs (SF1 expression), challenging the current definition of SF1/gonadotroph lineage. This classification improves our understanding and affects the clinical stratification of patients with PitNETs.

Thrombectomy by Direct Cervical Access in Case of Common Carotid Occlusion with Collateral Supply to Internal Carotid Artery: Uncommon Anatomic Variant.

BACKGROUND: Mechanical thrombectomy for acute ischemic stroke recently proved its superiority to standard medical management alone. With the increasing number of procedures, practitioners are exposed to unexpected situations that may lead to failure of access and significantly worse clinical outcome. Being able to plan the procedure and use alternative techniques may be useful in case of peculiar anatomy. CASE DESCRIPTION: We report here the case of a 60-year-old man referred to our institution for an acute ischemic stroke. The patient had an initial National Institutes of Health Stroke Scale score of 19. The patient's medical history revealed an unspecified cervical treatment at the level of C5-C6 20 years previously. Magnetic resonance imaging showed a left M1 occlusion and the absence of ipsilateral common carotid. The digital subtraction angiography revealed an anastomosis through the left inferior and superior thyroid artery. Mechanical thrombectomy was performed through direct cervical access with a TICI 3 recanalization score. CONCLUSIONS: Absence of viable access to perform mechanical thrombectomy during acute ischemic stroke is a rare but pejorative event. Direct common carotid puncture, even in its distal segment, when necessary is a feasible technique to perform internal carotid catheterization.

Biological and radiological exploration and management of non-functioning pituitary adenoma.

Non-functioning pituitary adenoma may be totally asymptomatic and discovered "incidentally" during radiological examination for some other indication, or else induce tumoral signs with compression of the optic chiasm and pituitary dysfunction. Non-functioning adenomas are mainly gonadotroph, but may also be "silent". Treatment strategy depends on initial clinical, biological, ophthalmological and radiological findings. The present French Society of Endocrinology Consensus work-group sought to update the pitfalls associated with hormone assay and outline a hormonal exploration strategy for diagnosis and follow-up, without overlooking the particularities of silent adenoma. We also drew up basic rules for initial exploration and radiological follow-up of both operated and non-operated pituitary adenomas.

Management of nonfunctioning pituitary incidentaloma.

Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy.

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences.

Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (P<0.0001), were associated with higher IGF1 levels (P=0.0001), invaded the cavernous sinus less frequently (P=0.0002), and rarely caused optic chiasm compression (P<0.0001). Acromegalic men tended to be younger at diagnosis than women (P=0.067) and presented higher IGF1 values (P=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (P=0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (P=0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether the T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies.

Therapeutic management of intracranial dural arteriovenous shunts with leptomeningeal venous drainage: report of 53 consecutive patients with emphasis on transarterial embolization with acrylic glue.

OBJECT: There is a strong correlation between the venous drainage pattern of intracranial dural arteriovenous shunts (ICDAVSs) and the affected patients' clinical presentation. The ICDAVSs that have cortical venous reflux (CVR) (retrograde leptomeningeal drainage: Borden Type 2 and 3 lesions) are very aggressive and have a poor natural history. Although the necessity of treatment remains debatable in ICDAVSs that drain exclusively into a sinus (Borden Type 1), lesions with CVR must be treated because of the negative effects of the retrograde venous drainage. Surgery, radiosurgery, and embolization have been proposed for management of these lesions, but endovascular therapy is considered the most appropriate therapeutic strategy in ICDAVSs. New embolic materials, such as Onyx, have been recently developed and are considered to represent a kind of "gold standard" for embolization of these lesions. The purpose of this study is to emphasize the importance of transarterial embolization using acrylic glue in the therapeutic management of ICDAVSs with CVR, and to compare the results the authors obtained using this treatment with those reported in the literature for Onyx treatment of the same type of dural shunts. METHODS: The clinical and radiological records of 53 consecutive patients suffering from ICDAVSs with CVR (Borden Types 2 or 3) were reviewed. All cases were managed with the same angiographic and therapeutic protocol. Localization of the lesions, their clinical symptoms, their angioarchitecture, their therapeutic management, and the results were analyzed. RESULTS: Fourteen ICDAVSs were located at the superior sagittal sinus and/or convexity veins, 13 at the transverse and sigmoid sinuses, 10 at the tentorium, 5 in the anterior cranial fossa, 4 at the foramen magnum, 3 at the torcula, 2 at the straight sinus, and 1 at the vein of Galen. One patient presented with an infantile form of ICDAVS with multiple shunts. Hemorrhage had occurred in 36% of cases. Forty-three patients underwent transarterial embolization (42 with acrylic glue). Complete closure of the fistula was obtained in 34 patients. Suppression of the CVR with partial occlusion of the main shunt was achieved in all other cases. No mortality or permanent morbidity was observed in this series. CONCLUSIONS: Intracranial dural arteriovenous shunts can be safely managed by transarterial embolization, which can be considered in most instances as an effective first-intention treatment. Acrylic glue still allows a cheap, fast, and effective treatment with high rates of cures that compare favorably to those obtained with new embolic materials.