Position statement on the diagnosis and management of congenital pituitary deficiency in adults: The French National Diagnosis and Treatment Protocol (NDTP).

Pituitary deficiency, or hypopituitarism, is a rare chronic disease. It is defined by insufficient synthesis of one or more pituitary hormones (growth hormone, TSH, ACTH, LH-FSH, prolactin), whether or not associated with arginine vasopressin deficiency (formerly known as diabetes insipidus). In adult patients, it is usually acquired (notably during childhood), but can also be congenital, due to abnormal pituitary development. The present study focuses on congenital pituitary deficiency in adults, from diagnosis to follow-up, including special situations such as pregnancy or the elderly. The clinical presentation is highly variable, ranging from isolated deficit to multiple deficits, which may be part of a syndromic form or not. Diagnosis is based on a combination of clinical, biological (assessment of all hormonal axes), radiological (brain and hypothalamic-pituitary MRI) and genetic factors. Treatment consists in hormonal replacement therapy, adapted according to the period of life and the deficits, which may be progressive. Comorbidities, risk of complications and acute decompensation, and the impact on fertility and quality of life all require adaptative multidisciplinary care and long-term monitoring.

Diagnosis and management of congenital hypopituitarism in children.

Hypopituitarism (or pituitary deficiency) is a rare disease with an estimated prevalence of between 1/16,000 and 1/26,000 individuals, defined by insufficient production of one or several anterior pituitary hormones (growth hormone [GH], thyroid-stimulating hormone [TSH], adrenocorticotropic hormone [ACTH], luteinizing hormone [LH], follicle-stimulating hormone [FSH], prolactin), in association or not with diabetes insipidus (antidiuretic hormone [ADH] deficiency). While in adults hypopituitarism is mostly an acquired disease (tumors, irradiation), in children it is most often a congenital condition, due to abnormal pituitary development. Clinical symptoms vary considerably from isolated to combined deficiencies and between syndromic and non-syndromic forms. Early signs are non-specific but should not be overlooked. Diagnosis is based on a combination of clinical, laboratory (testing of all hormonal axes), imaging (brain magnetic resonance imaging [MRI] with thin slices centered on the hypothalamic-pituitary region), and genetic (next-generation sequencing of genes involved in pituitary development, array-based comparative genomic hybridization, and/or genomic analysis) findings. Early brain MRI is crucial in neonates or in cases of severe hormone deficiency for differential diagnosis and to inform syndrome workup. This article presents recommendations for hormone replacement therapy for each of the respective deficient axes. Lifelong follow-up with an endocrinologist is required, including in adulthood, with multidisciplinary management for patients with syndromic forms or comorbidities. Treatment objectives include alleviating symptoms, preventing comorbidities and acute complications, and optimal social and educational integration.

Borrowing strength from adults: Transferability of AI algorithms for paediatric brain and tumour segmentation.

PURPOSE: AI brain tumour segmentation and brain extraction algorithms promise better diagnostic and follow-up of brain tumours in adults. The development of such tools for paediatric populations is restricted by limited training data but careful adaption of adult algorithms to paediatric population might be a solution. Here, we aim exploring the transferability of algorithms for brain (HD-BET) and tumour segmentation (HD-GLIOMA) in adults to paediatric imaging studies. METHOD: In a retrospective cohort, we compared automated segmentation with expert masks. We used the dice coefficient for evaluating the similarity and multivariate regressions for the influence of covariates. We explored the feasibility of automatic tumor classification based on diffusion data. RESULTS: In 42 patients (mean age 7 years, 9 below 2 years, 26 males), segmentation was excellent for brain extraction (mean dice 0.99, range 0.85-1), moderate for segmentation of contrast-enhancing tumours (mean dice 0.67, range 0-1), and weak for non-enhancing T2-signal abnormalities (mean dice 0.41). Precision was better for enhancing tumour parts (p < 0.001) and for malignant histology (p = 0.006 and p = 0.012) but independent from myelinisation as indicated by the age (p = 0.472). Automated tumour grading based on mean diffusivity (MD) values from automated masks was good (AUC = 0.86) but tended to be less accurate than MD values from expert masks (AUC = 1, p = 0.208). CONCLUSION: HD-BET provides a reliable extraction of the paediatric brain. HD-GLIOMA works moderately for contrast-enhancing tumours parts. Without optimization, brain tumor AI algorithms trained on adults and used on paediatric patients may yield acceptable results depending on the clinical scenario.

Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function.

BACKGROUND AND PURPOSE: Extent and dynamic of neurodegeneration in progressive multiple sclerosis (MS) might be reflected by global and regional brain perfusion, an outcome at the intercept between structure and function. Here, we provide a first insight into the evolution of brain perfusion and its association with disability in primary progressive MS (PPMS) over several years. METHODS: Seventy-seven persons with PPMS were followed over up to 5 years. Visits included a 3-T magnetic resonance imaging with pulsed arterial spin labelling perfusion, the Timed 25-Foot Walk, 9-Hole Peg Test (NHPT), Symbol Digit Modalities Test (SDMT), and Expanded Disability Status Scale (EDSS). We extracted regional cerebral blood flow surrogates and compared them to 11 controls. Analyses focused on cortical and deep grey matter, the change over time, and associations with disability on the regional and global levels. RESULTS: Baseline brain perfusion of patients and controls was comparable for the cortex (p = 0.716) and deep grey matter (p = 0.095). EDSS disability increased mildly (p = 0.023), whereas brain perfusion decreased during follow-up (p < 0.001) and with disease duration (p = 0.009). Lower global perfusion correlated with higher disability as indicated by EDSS, NHPT, and Timed 25-Foot Walk (p < 0.001). The motor task NHPT showed associations with 20 grey matter regions. In contrast, better SDMT performance correlated with lower perfusion (p < 0.001) in seven predominantly frontal regions, indicating a functional maladaptation. CONCLUSIONS: Decreasing perfusion indicates a putative association with MS disease mechanisms such as neurodegeneration, reduced metabolism, and loss of resilience. A low alteration rate limits its use in clinical practice, but regional association patterns might provide a snapshot of adaptive and maladaptive functional reorganization.

Automatic segmentation of deep grey nuclei using a high-resolution 7T magnetic resonance imaging atlas-Quantification of T1 values in healthy volunteers.

We present a new consensus atlas of deep grey nuclei obtained by shape-based averaging of manual segmentation of two experienced neuroradiologists and optimized from 7T MP2RAGE images acquired at (.6 mm)3 in 60 healthy subjects. A group-wise normalization method was used to build a high-contrast and high-resolution T1 -weighted brain template (.5 mm)3 using data from 30 out of the 60 controls. Delineation of 24 deep grey nuclei per hemisphere, including the claustrum and 12 thalamic nuclei, was then performed by two expert neuroradiologists and reviewed by a third neuroradiologist according to tissue contrast and external references based on the Morel atlas. Corresponding deep grey matter structures were also extracted from the Morel and CIT168 atlases. The data-derived, Morel and CIT168 atlases were all applied at the individual level using non-linear registration to fit the subject reference and to extract absolute mean quantitative T1 values derived from the 3D-MP2RAGE volumes, after correction for residual B1+ biases. Three metrics (the Dice and the volumetric similarity coefficients and a novel Hausdorff distance) were used to estimate the inter-rater agreement of manual MRI segmentation and inter-atlas variability, and these metrics were measured to quantify biases due to image registration, and their impact on the measurements of the quantitative T1 values was highlighted. This represents a fully automated segmentation process permitting the extraction of unbiased normative T1 values in a population of young healthy controls as a reference for characterizing subtle structural alterations of deep grey nuclei relevant to a range of neurological diseases.

High 18F-FDOPA PET Uptake in Primary Central Nervous System Lymphoma.

We present a 42-year-old woman with primary central nervous system lymphoma (PCNSL) and strong F-FDOPA PET uptake. F-FDOPA PET has high diagnostic accuracy in gliomas and brain metastases. The L-type amino acid transporter 1, targeted by F-FDOPA and C-MET PET, is a cell-type transporter usually upregulated in malignant tumors, including PCNSL. In this line, strong uptake was already shown with C-MET in PCNSL. We report the same findings with F-FDOPA. Consequently, PCNSL is a possible differential neoplastic diagnosis of F-FDOPA uptake among neoplastic lesions.

T1-Based Synthetic Magnetic Resonance Contrasts Improve Multiple Sclerosis and Focal Epilepsy Imaging at 7 T.

OBJECTIVES: Ultra-high field magnetic resonance imaging (MRI) (≥7 T) is a unique opportunity to improve the clinical diagnosis of brain pathologies, such as multiple sclerosis or focal epilepsy. However, several shortcomings of 7 T MRI, such as radiofrequency field inhomogeneities, could degrade image quality and hinder radiological interpretation. To address these challenges, an original synthetic MRI method based on T1 mapping achieved with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence was developed. The radiological quality of on-demand T1-based contrasts generated by this technique was evaluated in multiple sclerosis and focal epilepsy imaging at 7 T. MATERIALS AND METHODS: This retrospective study was carried out from October 2017 to September 2019 and included 21 patients with different phenotypes of multiple sclerosis and 35 patients with focal epilepsy who underwent MRI brain examinations using a whole-body investigative 7 T magnetic resonance system. The quality of 2 proposed synthetic contrast images were assessed and compared with conventional images acquired at 7 T using the MP2RAGE sequence by 4 radiologists, evaluating 3 qualitative criteria: signal homogeneity, contrast intensity, and lesion visualization. Statistical analyses were performed on reported quality scores using Wilcoxon rank tests and further multiple comparisons tests. Intraobserver and interobserver reliabilities were calculated as well. RESULTS: Radiological quality scores were reported higher for synthetic images when compared with original images, regardless of contrast, pathologies, or raters considered, with significant differences found for all 3 criteria (P < 0.0001, Wilcoxon rank test). None of the 4 radiologists ever rated a synthetic image "markedly worse" than an original image. Synthetic images were rated slightly less satisfying for only 3 epileptic patients, without precluding lesion identification. CONCLUSION: T1-based synthetic MRI with the MP2RAGE sequence provided on-demand contrasts and high-quality images to the radiologist, facilitating lesion visualization in multiple sclerosis and focal epilepsy, while reducing the magnetic resonance examination total duration by removing an additional sequence.

VNS implantation in a NF1 patient: massive nerve hypertrophy discovered intra-operatively preventing successful electrode placement. Case report.

For the vast majority of surgeons, no specific investigation is necessary before vagal nerve stimulation (VNS) implantation. We report our intraoperative unexpected finding of a massively enlarged vagus nerve in a patient with neurofibromatosis type 1 (NF1). The nerve hypertrophy prevented wrapping the coils of the helical electrode. The patient had no signs of vagus nerve dysfunction preoperatively (no hoarseness or dysphonia). This exceptional mishap is undoubtedly related to NF1-associated peripheral nerve sheath tumors. Even though it is not advisable to routinely perform any imaging prior to VNS, in such specific context, preoperative imaging work-up, especially cervical ultrasound, might be judicious to rule out any asymptomatic enlarged left vagus nerve.

Stroke after spontaneous intracranial hypotension: Not a single mechanism. Case report and review of literature.

Spontaneous intracranial hypotension (SIH) is a rare syndrome, typically manifests as orthostatic headache. Sometimes considered asbenignillness, neurological complications are well described, in particular subdural hematoma and cerebral venous sinus thrombosis. Brain infarction as complication of SIH is rarely reported. The main mechanism supported in the literature is the stretching of arteries due to the sagging of the brain. We report a case of SIH followed with brain infarction, with a distinct presentation from previous literature, suggesting a different mechanism. A 35 year-old had severe orthostatic headache, responsible for prolonged bed rest. One month later, he had acute left hemiparesis secondary to stroke and right posterior cerebral artery occlusion. Stroke MRI showed arguments for intracranial hypotension (thickened meninges). He was successfully treated with intravenous rtPA thrombolysis. Headache were resolved after an epidural blood patch. A patent foramen ovale was detected. Clinical features of this description were compared with previous literature. This case suggest a different mechanism for cerebral infarction after intracranial hypotension. In case of prolonged lying down due to intracranial hypotension, the presence of patent foramen ovale could be a risk factor for embolic stroke.

Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population.

PURPOSE: To evaluate the technical feasibility and efficacy of percutaneous cryoablation for the treatment of osteoid osteoma (OO) in adults. METHODS AND MATERIALS: 21 patients (12 male and nine female; mean age, 29.9 years) who underwent CT-guided percutaneous cryoablation for the treatment of OO were retrospectively evaluated. Procedures were carried out under local anaesthesia and conscious sedation in 13 patients, and under general anaesthesia in eight patients. Then, the ablation zone was evaluated with post-procedure magnetic resonance imaging at 6 weeks. Clinical outcome was assessed using a visual analogue scale (VAS) to evaluate severity of pain before procedure, as well as at primary (6 weeks) and secondary follow-up (6-40 months). RESULTS: All procedures were technically successful. Median VAS scores were: 8 (range, 5-10) before procedure and after procedure, respectively, 0 (range, 0-2; p < .0001) and 0 (range, 0-7; p < .0001) at primary and secondary follow-up. There were three minor complications (14.3%) and no major complication. A single patient reported symptom recurrence (4.8%) at secondary follow-up and successfully underwent a second cryoablation procedure. CONCLUSION: CT-guided percutaneous cryoablation is safe and effective in the treatment of OO in adults, and can be accomplished without general anaesthesia in selected cases. KEY POINTS: • CT-guided percutaneous cryoablation of osteoid osteoma is safe and effective • Cryoablation allows precise visual control of the aggregated iceball during procedure • Percutaneous cryoablation can be accomplished without general anaesthesia in selected cases • Another advantage of cryoablation is reduction of immediate postprocedural pain • Post-procedure MRI is helpful in the evaluation of technical success.