Auswahl der wissenschaftlichen Literatur zum Thema „Radiologically Isolated Syndrom“

Objective:To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed “radiologically isolated syndrome” or RIS).Methods:Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS.Results:We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%–60%) in a median of 2.0 years (interquartile range [IQR] 1.0–4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%–76%) in a median of 1.1 years (IQR 0.5–1.9 years). The presence of ≥2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4–86.2, p = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4–43.6, p = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex.Conclusions:We describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.

Le Syndrome Radiologique Isolé (RIS pour Radiologically Isolated Syndrome) représente la phase pré-clinique de la sclérose en plaques (SEP), et correspond à la découverte fortuite d'anomalies de la substance blanche évocatrices de SEP de par leur localisation, leur taille et leur forme, sur une Imagerie par Résonance Magnétique (IRM) pratiquée pour une autre raison que pour une suspicion de maladie démyélinisante chez des sujets sans histoire de symptôme neurologique et présentant un examen clinique neurologique strictement normal. Les critères diagnostiques de RIS ont été décrits la première fois en 2009 et révisés en 2023 augmentant la sensibilité des critères mais aussi les risques d'erreurs de diagnostic. Ce constat a été à l'origine du premier travail de cette thèse portant sur une enquête française d'identification des lésions de la substance blanche en IRM montrant que de nombreux praticiens utilisent les critères de diagnostic de la SEP même si les anomalies de la substance blanche ne correspondent pas à des lésions démyélinisantes, pouvant engendrer des erreurs dans l'application des critères de diagnostic de SEP. Ces résultats soulignent l'importance d'avoir des marqueurs diagnostiques dans la pratique courante.La seconde étude de cette thèse porte sur l'évaluation d'un marqueur diagnostic appelé « signe de la veine centrale » (SVC) dans le diagnostic de RIS. En effet, des études récentes utilisant l'IRM à haute résolution et notamment une séquence spécifique en IRM de susceptibilité magnétique, la SWI (Susceptibility-Weighted Imaging), permet de mettre en évidence ce SVC. L'IRM obligatoire pour le diagnostic et du suivi du RIS, l'identification de marqueur diagnostic comme le SVC permet d'augmenter la spécificité et la sensibilité du diagnostic et de réduire les erreurs diagnostiques. Une fois le diagnostic de RIS certain et établi, l'identification de marqueurs prédictifs de conversion clinique en SEP constitue un enjeu crucial pour les patients RIS.Le troisième objectif de cette thèse porte sur l'étude du volume des plexus choroïdes dans une large cohorte de patients RIS en comparaison avec des sujets sains afin d'explorer sa relation avec d'autres volumes cérébraux, mais aussi l'activité clinique et radiologique de la maladie et avec des marqueurs biologiques identifiés en parallèle dans notre équipe.La prochaine étape de ce travail sera d'introduire une analyse de biomarqueurs digitaux. En effet, nous avons démontré que des sujets RIS montrent de moins bonnes performances que des sujets contrôles à la passation de tests digitaux à partir de l'utilisation d'applications mobiles. Nous émettons l'hypothèse que des mesures digitales, collectées de façon simple à l'aide d'un smart phone ou d'une tablette, permettraient de déceler des anomalies infracliniques qui témoigneraient d'une évolution silencieuse de la maladie et seraient prédictives d'une évolution clinique.Ce projet de thèse porte principalement sur l'analyse de biomarqueurs en imagerie dans le but d'améliorer le diagnostic de RIS mais aussi dans l'objectif d'identifier des facteurs prédictifs d'évolution clinique des sujets RIS en SEP
Radiologically Isolated Syndrome (RIS) is the pre-clinical phase of multiple sclerosis (MS). It corresponds to the incidental discovery of white matter abnormalities suggestive of MS based on their location, size, and shape on Magnetic Resonance Imaging (MRI) performed for a reason other than for suspicion of demyelinating disease in subjects with no history of neurological symptoms and presenting a strictly normal neurological clinical examination. The diagnostic criteria for RIS were first described in 2009 and revised in 2023, increasing the sensitivity of the criteria and the risks of diagnostic errors. This observation was at the origin of the first work of this thesis relating to a French survey of identification of white matter lesions in MRI showing that many practitioners use the diagnostic criteria for MS even if white matter abnormalities do not correspond to demyelinating lesions, which may cause errors in the application of the MS diagnostic criteria. These results highlight the importance of having diagnostic markers in current practice.The second study of this thesis focuses on the evaluation of a diagnostic marker called “central vein sign” (CVS) in the diagnosis of RIS. Indeed, recent studies using high-resolution MRI and a specific magnetic susceptibility sequence, SWI (Susceptibility-Weighted Imaging), make it possible to visualize this CVS. As MRI is mandatory for the diagnosis and monitoring of RIS, the identification of diagnostic markers such as CVS makes it possible to increase the specificity and sensitivity of the diagnosis and to reduce diagnostic errors. Once the diagnosis of RIS is certain and established, identifying predictive markers of clinical conversion to MS constitutes a crucial issue for RIS patients.The third objective of this thesis involves the study of the volume of the choroid plexuses in a large cohort of RIS patients compared with healthy control subjects to explore its relationship with other brain volumes, clinical and radiological activity of the disease, and biological markers.The next step in this work will be to introduce an analysis of digital biomarkers. Indeed, we have demonstrated that RIS subjects perform poorer than control subjects facing digital tests using mobile applications. We hypothesize that digital measurements, collected easily using a smartphone or a tablet, would make it possible to detect subclinical anomalies, which would indicate a silent evolution of the disease and predict a clinical evolution.This thesis project mainly focuses on analyzing biomarkers in imaging to improve the diagnosis of RIS and identify predictive factors of the clinical evolution of RIS subjects in MS

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
A Síndrome Radiológica Isolada (RIS) corresponde a uma situação clínica em que são identificadas em exames de imagem, nomeadamente de ressonância magnética (RM), lesões de características desmielinizantes consideradas típicas de esclerose múltipla (EM), sem que o indivíduo tenha tido, em algum momento, qualquer manifestação clínica a elas atribuível. Por este motivo, é a RIS habitualmente considerada como uma fase pré-sintomática da EM, o que a torna um alvo de investigação extremamente apetecível, no sentido de se modificar o risco de que se venha a desenvolver essa mesma doença. A RIS pode ser diagnosticada em idade pediátrica, mas são extremamente escassos os dados existentes sobre esta condição, de manifestação tão precoce na vida. Neste trabalho, far-se-á uma revisão narrativa sobre a RIS em idade pediátrica, refletindo-se criticamente sobre o benefício do seu estudo, particularmente para o (eventual) desenvolvimento de estratégias terapêuticas promotoras da remielinização e neuroprotecção. .
Radiologically Isolated Syndrome (RIS) is a condition in which imagiological findings suggestive of demyelination, specifically multiple sclerosis, are seen in neurologically asymptomatic individuals. Hence, RIS is usually referred to as a pre-symptomatic stage of multiple sclerosis, making it an interesting research object, with the goal of modifying the risk of subsequent evolution to that demyelinating disease. RIS can be diagnosed in children and adolescents, but the data available on this condition for this age range is still scarce. This review on pediatric RIS focuses on the benefit of its research, specifically aiming at the eventual development of therapeutic interventions that, in the future, will eventually promote remyelination and neuroprotection. .

This chapter aims to highlight the diagnostic and prognostic value of cerebrospinal fluid (CSF) findings in multiple sclerosis with a special consideration of distinguishing it from neuromyelitis optica (NMO) and NMO spectrum disorder. Interpretation of CSF findings in daily clinical practice in patients with MS is thoroughly explained. New advances in CSF analysis and recently identified biomarkers may be helpful for diagnosis, help elucidate disease subtype and activity, or aid in prognosis and monitoring of the response to treatment. Characteristics of CSF changes in different subtypes of multiple sclerosis, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS) are discussed. CSF findings in NMO spectrum disease as a diagnostic and differentiating marker are explained separately.

Vascular surgical patients are at higher risk of cardiovascular morbidity and mortality than other surgical patients, and perioperative care remains challenging. However, vascular surgical practice is changing, with the expanding use of endovascular techniques to treat patients with vascular disease, improvements in medical therapy, and the evolution of evidence-based approaches to preoperative assessment. Preoperative assessment should concentrate on identifying and optimizing potentially correctable medical conditions, in particular cardiovascular disease. Successful outcomes depend on good anaesthetic techniques with emphasis on meticulous attention to detail and maintaining cardiovascular function and stability. Good communication with surgical and radiological colleagues is also vital. Anaesthesia for major vascular surgery also requires expertise in managing major haemorrhage, the use of invasive monitoring and cardioactive drugs, and regional anaesthesia. Knowledge and skills in the use of specific techniques for monitoring and protection against organ dysfunction are required. Endovascular surgery may be performed in dedicated operating suites or within the radiology department so the anaesthetist needs to be aware of considerations for anaesthesia in an isolated environment. This chapter details the management of patients presenting for the commonest major vascular procedures. All aspects of perioperative care for patients with abdominal and thoracic aortic aneurysms, occlusive aortic and peripheral vascular disease, and carotid stenosis are discussed. Anaesthesia for open surgery, endovascular and hybrid procedures, and elective and emergency procedures are included. The benefits of regional and general anaesthetic techniques are considered, where appropriate. The chapter also incorporates the anaesthetic management for less common procedures to treat carotid body tumours, thoracic outlet syndrome, and for thoracoscopic sympathectomy.

A healthy 26-year-old woman with a history of episodic migraine without aura since age 12 years had a first-ever event of transient visual impairment. She reported to her neurologist that she “lost vision” for 15 minutes and described a “black blob” with a bright jagged border that moved across her binocular visual field and resolved without sequelae. Minutes later, one of her typical migraine headaches developed. Given the patient’s history of typical episodic migraine, the new visual event’s clinical characteristics were highly consistent with a migraine aura. Because of the new transient visual symptoms, the neurologist ordered brain magnetic resonance imaging, which showed several periventricular white matter lesions, including some that involved the corpus callosum and were oriented perpendicular to the septocallosal surface. The patient was counseled about the magnetic resonance imaging findings and expressed the desire to fully evaluate her risk of multiple sclerosis. The patient was diagnosed with radiologically isolated syndrome. The patient was counseled regarding the relevance of the magnetic resonance imaging findings and risk of future development of multiple sclerosis. She was not prescribed a disease-modifying therapy for multiple sclerosis. This patient has radiologically isolated syndrome —incidentally found magnetic resonance imaging lesions consistent with demyelination in a patient with no symptoms or signs suggestive of multiple sclerosis.

• The pituitary is formed of two anatomically and embryologically distinct lobes: ◦ anterior pituitary: which secretes growth hormone (GH), gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin ◦ posterior pituitary: which secretes vasopressin and oxytocin. • Hypopituitarism is deficiency of one or more pituitary hormones. Some hormones, e.g. GH (LH/FSH), are more likely to present with isolated deficiencies, while others, e.g. TSH, ACTH, are more often found as part of multiple pituitary hormone deficiency (MPHD). • Deficiencies may be congenital (including genetic) or acquired; secondary to tumour, trauma, infiltration, infection, or irradiation. • GH deficiency: ◦ diagnosed using a combination of clinical, radiological, and biochemical assessment (including GH stimulation testing) ◦ treatment is with GH (including if necessary into adulthood). • LH/FSH deficiency: ◦ If acquired, often one of the first anterior pituitary hormones to be lost. ◦ Congenital forms: ■ present with cryptorchidism and/or micropenis in males ■ may occur in isolation, or in association with anosmia (Kallmann and CHARGE syndromes). ◦ Treatment: sex steroid therapy to induce secondary sexual characteristics, and recombinant FSH/LH to induce fertility potential. • ACTH deficiency: ◦ Unlike primary adrenal problems, hyperpigmentation does not occur. ◦ Although mineralocorticoid production is preserved, hyponatraemia may still occur. ◦ Treatment is with hydrocortisone. • TSH deficiency: ◦ TSH may be low, normal, or raised (but inappropriate for free thyroxine level). ◦ Treatment is with thyroxine. • Vasopressin deficiency: ◦ produces cranial diabetes insipidus ◦ treatment is with DDAVP (orally or nasally). • Prolactin and oxytocin deficiency rarely produce clinical problems.

Context: The Red Ear Syndrome” (RES) is a rare condition characterized by ear hyperemia associated with burning pain. This syndrome is classified into secondary and idiopathic forms, which pathophysiological mechanisms are still unclear. Idiopathic forms occur isolated or associated with primary headaches and secondary forms are associated to cervical disorders. The aim of this study is to report a case of RES related to migraine, the new published cases make this syndrome earn more attention and investigation. Case report: A 31-year-old woman presented with acute pain, edema and marked erythema, occasionally accompanied by hyperhidrosis and local burning. These episodes occurred spontaneously or were induced by triggers. During attacks, cooling was the only means of relief. The patient reported a clear association between RES and some migraine attacks. Extensive laboratory and radiological investigation showed no abnormalities. Conclusions: RES is mainly determined by sudden or induced attacks of burning pain and redness in the ear. Attacks can last from minutes to hours in conjunction with primary headaches. The uncertainty about the etiology of this syndrome is an obstacle to treatment.

In 1980, Hall et all described a syndrome characterized by “hamartoblastoma”, hypopituitarism, unperfurated anus, polydactyly postaxial and numerous visceral anomalies, today known as Pallister-Hall Syndrome. On the study, Hall et all reported six cases of children with that malformation syndrome - lethal on neonatal period. None of the newborns had anterior hypophysis and the hypothalamic tumor was apparent in the inferior part of the brain, going from the optic chiasm to the interpeduncular fossa. Besides, other anomalies were found, such as: laryngeal split, abnormal pulmonary lobation, renal agenesis or dysplasia, shorts fourth metacarpals, nail dysplasia, multiple mouth frenulum, hypoadrenalism, congenital cardiomyopathy and intrauterine growth retardation. Every case was sporadic, the chromosome were apparently normal, without consaguinity relations. Several similar, milder and even asymptomatic cases were described later on. Kletter and Biesecker (1992), Topf et all (1993) and Penman Splitt et all (1994), define the disease as dominant autosomal inheritance. Kettler and Biesecker (1992) stated that most cases as sporadic as a result of a gene mutation with variable expressiveness. According to Biesecker et al (1996), an international workshop determined diagnostic criteria to the Syndrome: Hypothalamic Hamartroma and Central Polydactyly; First degree relative with hypothalamic hamartroma and polydactyly; Dominant autosomal parrent inheritance or in a consistent form with germaine mosaicism. The radiological changes are important for differential diagnosis between Pallister-Hall Syndrome and other hamartroma-present diseases. The hypothalamic hamartroma isolated has phenotypical features and causes hormonal disorders such as early puberty. On the MRI (Magnetic resonance imaging) it shows hyperintese sign on attenuated fluid. On the other hand, the Pallister-Hall Syndrome the hamartroma shows itself as a isointense signs along with other deformities as polydactyly, for example. According to Kuo et al (1999), on MRI, the classic hypothalamic hamartroma isn’t calcified, is homogenous and isointense to the grey matter on weight images in T1, and isointense and often hyperintense on weight images in T2. Those findings are pretty distinctive and help distinguish the hypothalamic hamartroma from ordinary lesions, as craniopharyngioma and hypothalamic/opticalchiasmic glioma, observed in children. Case report: The patient ALDV, male, born in 30/12/1995, was referred to evaluation on the Medical Genetic Service from HCPA. At the time, aged one year and 8 months, he was the only son of a young, healthy couple with no consanguinity. The family history of similar cases or other genetic pathologies are unknown. The prenatal happened with no intercurrences, unless the smoking mother. It was a natural birth; Birth Weight: 2kg; High: 42cm; PC: 32cm. APGAR 9. At 8 months, starts an investigation for precocious puberty, and a karyotype was performed in her hometown: 46, XY (normal). He presents convulsive crises since one year old. DNPM: cephalic support when he had 8 months, sat without support at the age of one. Physical examination: Head circumference in the 97th percentile, length above the 97th percentile. Good general condition, dysmorphic, facies with fusion of eyebrows (sinofre), epicanthus, small nose, dysplastic ears with a broad shield, three café-au-lait spots on the body. Presence of pubic hair. Increase in length and diameter of the penis, as well as of the testicles, in relation to chronological age. In the hands, significant brachydactyly with bitateral hexadactyly. In the feet, bilateral hexadactyly. Proximal cutaneous syndactyly between the 2nd and 3rd bilateral arthroids, mainly on the right. Additional exams: Rx of hands and wrists for bone age: 7 years; Chronological Age: 1 year and 10 months. Normal abdominal ultrasound; Computed Tomography of Skull/Magnetic Resonance of Skull: hypothalamic expansive lesion (3 cm), compatible with hamartoma; triventricular hydrocephalus; Cavum septum pellucidum. Endocrinological Evaluation: compatible with precocious puberty of central cause. High resolution karyotype: 46, XY (normal). Computed tomography of the brain: Examination for neurological control, performed on 10/12/2014, 18-year-old patient. It was observed solid nodular formation in the hypothalamic region, hypodense, with well-defined limits, in close contact with the mesencephalon, without impregnation by contrast medium administered intravenously, measuring about 2.9 X 2.4 X 3.0 cm, in the respective laterolateral, anteroposterior and craniocaudal planes, which in correlation with the patient’s clinical history may be related to hypothalamic Hamartoma.