Le syndrome d’Alström : étude descriptive des anomalies cérébro-faciales à l’IRM

Médecine. Radiodiagnostic. Imagerie médicaleIntroduction : Le syndrome d'Alström (SA) est une ciliopathie génétique rare caractérisée par une perte progressive visuelle par rétinite pigmentaire, une perte auditive neurosensorielle, une obésité, un diabète insulinorésistant, une cardiomyopathie dilatée et une petite taille. Cette étude vise à décrire les manifestations crânio-faciales et cérébrales du syndrome d'Alström à l'IRM. Matériel et méthodes : Dans cette étude prospective monocentrique non contrôlée, dix-sept patients atteints du syndrome d'Alström confirmé génétiquement (âge moyen, 17,12 ans ; intervalle, 6-46 ans ; 10 femmes) ont eu une imagerie par IRM cérébrale. Le protocole de l'étude comprenait des séquences 3D T2 FLAIR, des séquences 3D T1 IR et une séquence T2 haute résolution axée sur les bulbes olfactifs. Les images ont été analysées pour rechercher une atrophie cérébelleuse, une atrophie des bulbes olfactifs, une atteinte de l'hypophyse définie par une selle turcique vide, une dysgénésie hippocampique, des anomalies de la substance blanche et leur localisation, une obstruction des sinus de la face ou des anomalies des oreilles interne et moyenne. Résultats : Une atrophie cérébelleuse a été observée dans tous les cas et 14/17 présentaient une atrophie supra-tentorielle (prédominance fronto-pariétale). 10/17 patients présentaient une dysgénésie de l'hippocampe, 8/17 présentaient des anomalies de la substance blanche. 4/17 avaient une selle turcique vide. Un comblement sinusien était noté chez 10/17 patients. Cliniquement, 6/17 patients présentaient des troubles olfactifs. Les valeurs moyennes de l'évaluation volumétrique des deux bulbes olfactifs étaient de 34,23 mm3. Aucune atrophie du nerf acoustique n'a été détectée. 2 malformations labyrinthiques postérieures bénignes ont été observées. Conclusion : Cette étude originale d’analyse cérébro-faciale dans le syndrome d’Alström a permis de mettre en évidence une atrophie cérébelleuse, une hypotrophie des bulbes olfactifs, une atteinte de l’hypophyse définie par une selle turcique vide, une dysgénésie hippocampique, des hypersignaux de la substance blanche, un comblement inflammatoire des sinus de la face et une absence d’atteinte des nerfs optiques et auditifs dans un contexte de cécité et de surdité profonde. Elle permet d’ouvrir le champ à de futures études de corrélation radiologique/génotype-phénotype et d’améliorer la connaissance de cette ciliopathie rare.Background and Purpose: Alström Syndrome (AS) is a rare genetic ciliopathy characterized by cone-rod retinal dystrophy, sensorineural hearing loss, obesity, endocrinal dysfunctions, insulin-resistant diabetes, cardiomyopathy and short stature. This study aims to describe the cranio facial and brain MRI manifestations of AS. Material - Methods: In this monocentric prospective non-controlled study, seventeen patients with genetically assessed AS (mean age, 17,12 years; range, 6-46 years; 10 females) underwent brain MR imaging. The study protocol included 3D T2 FLAIR, 3D T1 IR sequences, and high-resolution T2 sequence focused on olfactive bulbs. Images were analysed to search cerebellar atrophy, olfactive bulbs atrophy, pituitary gland involvement defined by an empty sella, hippocampal dysgenesis, white matter abnormalities and their localization, sinus fillings or abnormalities of inner and middle ear. Results: Cerebellar atrophy was observed in 16/17 cases and 14/17 had supra tentorial atrophy (fronto parietal predominance). 10/17 patients demonstrated hippocampal dysgenesis, 6/17 had white matter abnormalities. 2/17 patients presented an arachnoid cyst. 1/17 had a mega cisterna magna. 4/17 had an empty dorsal sella, sinus fillings on 10/17 patients. The mean values of both olfactive bulbs volumetric evaluation was 34,23 mm3. No acoustic nerve atrophy was detected. 2 benign posterior labyrinthic malformations were observed. Conclusion: Brain involvement in AS is constant in our series. The most common anomaly found is a cerebral atrophy, mainly affecting the cerebellum. The high rate of hippocampal dysgenesis, hypotrophy of the olfactive bulbs and empty dorsal sella is questioning and need to be correlate with the study of their function. It opens the field to future radiological/genotype-phenotype correlation studies and improves knowledge of this rare ciliopathy

Cerebral vasculitis of medium-sized vessels as a possible mechanism of brain damage in COVID-19 patients

Background and purpose: Cerebral complications related to COVID-19 were recently reported, and the underlying mechanisms of brain damage remain uncertain, probably multifactorial. Among various hypotheses suggested, a possible vasculitis was issued but never confirmed. Herein, we aimed to describe brain MRIs focused on the intracranial vessel wall in a population of COVID-19 patients with neurologic manifestations.Materials and methods: Between March 1 and May 31, 2020, 69 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI allowing the study of the intracranial vessel wall at Strasbourg University hospitals and were retrospectively included. During the same period, 25 consecutive patients, without suspicion of SARS-CoV-2 infection, underwent a brain MRI urgently, with the same imaging protocols. A vasculitis seemed likely when imaging demonstrated vessel wall thickening with homogeneous and concentric enhancement.Results: Among the 69 COVID-19 patients included, 11 (16%) presented arterial vessel wall thickening with homogeneous and concentric enhancement, compatible with cerebral vasculitis. These neuroimaging findings were not found among the 25 patients without SARS-CoV-2 infection, and the difference was statistically significant (p = 0.03). Middle cerebral arteries, basilar artery, and posterior cerebral arteries were the most frequent vessels involved. For nine of them, imaging demonstrated ischemic or hemorrhagic complications.Conclusion: Cerebral vasculitis of medium-sized vessels seems to be one of the mechanisms at the origin of brain damage related to COVID-19

Collicular Hyperactivation in Patients with COVID-19: A New Finding on Brain MRI and PET/CT

Hyperactivation of the colliculi has been observed in some patients with coronavirus disease 2019

Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses

Background and purpose: During the COVID-19 outbreak, the presence of extensive white matter microhemorrhages was detected by brain MRIs. The goal of this study was to investigate the origin of this atypical hemorrhagic complication. Methods: Between March 17 and May 18, 2020, 80 patients with severe COVID-19 infections were admitted for acute respiratory distress syndrome to intensive care units at the University Hospitals of Strasbourg for whom a brain MRI for neurologic manifestations was performed. 19 patients (24%) with diffuse microhemorrhages were compared to 18 control patients with COVID-19 and normal brain MRI. Results: The first hypothesis was hypoxemia. The latter seemed very likely since respiratory failure was longer and more pronounced in patients with microhemorrhages (prolonged endotracheal intubation (p = 0.0002), higher FiO2 (p = 0.03), increased use of extracorporeal membrane oxygenation (p = 0.04)). A relevant hypothesis, the role of microangiopathy, was also considered, since patients with microhemorrhages presented a higher increase of the D-Dimers (p = 0.01) and a tendency to more frequent thrombotic events (p = 0.12). Another hypothesis tested was the role of kidney failure, which was more severe in the group with diffuse microhemorrhages (higher creatinine level [median of 293 µmol/L versus 112 µmol/L, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04). Conclusions: Blood-brain barrier dysfunction secondary to hypoxemia and high concentration of uremic toxins seems to be the main mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients. Keywords: COVID-19; Hypoxemia; Kidney failure; MRI; Microhemorrhages

Molecular Heterogeneity in BRAF-Mutant Gliomas: Diagnostic, Prognostic, and Therapeutic Implications

Over the last few decades, deciphering the alteration of molecular pathways in brain tumors has led to impressive changes in diagnostic refinement. Among the molecular abnormalities triggering and/or driving gliomas, alterations in the MAPK pathway reign supreme in the pediatric population, as it is encountered in almost all low-grade pediatric gliomas. Activating abnormalities in the MAPK pathway are also present in both pediatric and adult high-grade gliomas. Across those alterations, BRAF p.V600E mutations seem to define homogeneous groups of tumors in terms of prognosis. The recent development of small molecules inhibiting this pathway retains the attention of neurooncologists on BRAF-altered tumors, as conventional therapies showed no significant effect, nor prolonged efficiency on the high-grade or low-grade unresectable forms. Nevertheless, tumoral heterogeneity and especially molecular alteration(s) associated with MAPK-pathway abnormalities are not fully understood with respect to how they might lead to the specific dismal prognosis of those gliomas and/or affect their response to targeted therapies. This review is an attempt to provide comprehensive information regarding molecular alterations related to the aggressiveness modulation in BRAF-mutated gliomas and the current knowledge on how to use those targeted therapies in such situations

Cerebral mucormycosis: neuroimaging findings and histopathological correlation

International audienceIntroduction: Mucormycosis are infections caused by molds of the order Mucorales. These opportunistic infections are rare, difficult to diagnose, and have a poor prognosis. We aimed to describe common radiographic patterns that may help to diagnose cerebral mucormycosis and search for histopathological correlations with imaging data. Methods: We studied the radiological findings (CT and MRI) of 18 patients with cerebral mucormycosis and four patients' histopathological findings. Results: All patients were immunocompromised and/or diabetic. The type of lesions depended on the infection's dissemination pathway. Hematogenous dissemination lesions were most frequently abscesses (59 lesions), cortical, cortical-subcortical, or in the basal ganglia, with a halo aspect on DWI for lesions larger than 1.6 cm. Only seven lesions were enhanced after contrast injection, with different presentations depending on patients' immune status. Ischemia and hemorrhagic areas were also seen. Vascular lesions were represented by stenosis and thrombosis. Direct posterior extension lesions were bi-fronto basal hypodensities on CT and restricted diffusion without enhancement on MRI. A particular extension, perineural spread, was seen along the trigeminal nerve. Histopathological analysis found endovascular lesions with destruction of vessel walls by Mucorales, microbleeds around vessels, as well as acute and chronic inflammation. Conclusions: MRI is the critical exam for cerebral mucormycosis. Weak ring enhancement and reduced halo diffusion suggest the diagnosis of fungal infections. Involvement of the frontal lobes should raise suspicion of mucormycosis (along with aspergillosis). The perineural spread can be considered a more specific extension pathway of mucormycosis

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty

Evolution of Neuroimaging Findings in Severe COVID-19 Patients with Initial Neurological Impairment: An Observational Study

Background and Objectives: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. Methods: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). Results: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18–79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. Conclusion: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery

Periodontal (formerly type VIII ) Ehlers–Danlos syndrome: Description of 13 novel cases and expansion of the clinical phenotype

International audienc