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Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the etiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analyzed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.

Cavernous malformations (CM) of the brain are vascular abnormalities that carry a risk of bleeding, posing significant neurological and life-threatening challenges, particularly in posterior fossa. The efficacy of radiosurgery for cavernomas still remains a matter of debate, largely due to technical and statistical limitations. In this study, we present a series of posterior fossa cavernomas treated using CyberKnife radiosurgery, employing an innovative approach that integrates both technical and statistical advancements. Patients and methods: We conducted a prospective series involving 35 posterior fossa cavernomas in 33 patients treated with low-dose radiosurgery protocols (12 Gy in a single fraction or 18 Gy in 3 fractions). Compared to previously published series, our approach targeted a larger treatment volume, encompassing the entire hemosiderin ring surrounding the cavernoma. Radiosurgery was indicated for cases of hemorrhage or progressive neurological deficits in anatomically challenging, nonsurgical areas. The statistical analysis was designed to address the unknown onset time of cavernoma prior to radiosurgery, enabling a more accurate calculation of the hemorrhage incidence rate before treatment. Follow-up evaluations, including clinical assessments and MRI, were conducted at 3-6-9-12-18-24 months and subsequently on an annual basis. Results: With a mean follow-up duration of 26 months, exceeding the previously described latency period, and a median [IQR] follow-up of 13 months [8.7-30.4] which represents approximately half the latency period, only one patient experienced a recurrence of hemorrhage, occurring 20 months post-treatment and remaining asymptomatic. No patients exhibited radio-induced parenchymal changes or clinical deterioration following radiosurgery. Conclusions: These preliminary results support the strategy of increasing the target volume while reducing the radiation dose for cavernous malformations. We further recommend incorporating sensitivity analyses to evaluate the robustness of results, particularly in the context of uncertainties surrounding the time of onset of cavernomas. [ABSTRACT FROM AUTHOR]

Résumé: Les maladies des petits artères cérébrales (MPAC) sont une cause fréquente d'accidents vasculaires cérébraux (AVC), qu'ils soient ischémiques ou hémorragiques. Une petite proportion des MPAC résulte de pathologies monogéniques. Bien qu'elles soient rares, l'identification de ces formes monogéniques est cruciale, permettant d'offrir une prise en charge adaptée à ces patients et à leurs apparentés. Dans cette revue, les principales situations devant conduire le clinicien à évoquer une forme monogénique de MPAC sont listées, et les principales caractéristiques des différentes MPAC connues à ce jour sont résumées. Cerebral small vessel diseases (cSVD) represent a common cause of stroke, either ischemic or hemorrhagic. Only a small proportion of cSVD results from monogenic conditions. Although they are involved in a minority of patient, the accurate identification by physicians of hereditary forms of cSVD is crucial for the medical care of these patients and their relatives. In this paper, the main situations that must lead physicians to suspect a hereditary cSVD are listed, and the key characteristics of the monogenic cSVD known to date are summarized. [ABSTRACT FROM AUTHOR]

Résumé: Nous rapportons le cas d'une patiente présentant un accident vasculaire cérébral (AVC) ischémique, secondaire à un thrombus de la carotide interne, sur plaque d'athérome. La taille du thrombus et son association à une embolie pulmonaire sont inhabituels et le seul facteur favorisant potentiel identifié est le contexte de Covid-19, sans signe de gravité de l'infection. La survenue de volumineuses thromboses artérielles au cours de la maladie liée au coronavirus est largement rapportée depuis le début de l'épidémie. Ce phénomène, responsable notamment d'AVC ischémiques sévères, ne survient pas nécessairement chez des patients présentant une forme grave de l'infection, mais semble associé à un moins bon pronostic fonctionnel. We report a case of ischemic stroke characterized by unusual large thrombosis of the internal carotid, origin associated to pulmonary embolism in a patient without any prothrombotic factor except from mild signs of Covid-19. The high incidence of thrombotic phenomens observed among patients with coronavirus during the last months does not seem to systematically occur among patients with severe presentation of the infection, but seems associated to a worst functional prognosis. [ABSTRACT FROM AUTHOR]

Moyamoya angiopathy is characterized by a progressive stenosis of the terminal portion of the internal carotid arteries and the development of a network of abnormal collateral vessels. This chronic cerebral angiopathy is observed in children and adults. It mainly leads to brain ischemic events in children, and to ischemic and hemorrhagic events in adults. This is a rare condition, with a marked prevalence gradient between Asian countries and Western countries. Two main nosological entities are identified. On the one hand, moyamoya disease corresponds to isolated moyamoya angiopathy, defined as being "idiopathic" according to the Guidelines of the Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis. This entity is probably multifactorial and polygenic in most patients. On the other hand, moyamoya syndrome is a moyamoya angiopathy associated with an underlying condition and forms a very heterogeneous group with various clinical presentations, various modes of inheritance, and a variable penetrance of the cerebrovascular phenotype. Diagnostic and evaluation techniques rely on magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) conventional angiography, and cerebral hemodynamics measurements. Revascularization surgery can be indicated, with several techniques. Characteristics of genetic moyamoya syndromes are presented, with a focus on recently reported mutations in BRCC3/ MTCP1 and GUCY1A3 genes. Identification of the genes involved in moyamoya disease and several monogenic moyamoya syndromes unraveled different pathways involved in the development of this angiopathy. Studying genes and pathways involved in monogenic moyamoya syndromes may help to give insights into pathophysiological models and discover potential candidates for medical treatment strategies. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation Intravascular lymphoma is a rare subtype of B‐cell lymphoma characterized by a clonal proliferation restricted to the lumen of small vessels. Over 50% of patients exhibit central nervous system (CNS) involvement, but diagnosis is often delayed due to the lack of distinctive features. We aimed to identify key phenotypic features for early diagnosis of intravascular lymphoma with CNS involvement through an in‐depth cohort study.We built up a multicenter retrospective cohort of 17 patients recruited in collaboration with the French Expert Network for Oculo‐Cerebral Lymphomas (LOC network), and retrospectively analyzed data from medical records.In this cohort, 15 of 17 (88%) patients developed focal neurological episodes, often fluctuating and/or recurrent, with a sudden onset in 68% of episodes, suggesting a vascular origin. Rapid cognitive deterioration occurred in 15 of 17 (88%) patients, psychiatric manifestations in 8 of 17 (47%), and “B signs” in 14 of 17 (82%). Brain MRI showed polymorphic FLAIR hyperintensities in 14 of 16 (87%) patients, and DWI‐positive lesions in 13 of 16 (81%) of patients, which accumulated over time and had unusual characteristics for ischemic lesions (progressive growth, persistent DWI‐hyperintensity over 1 month, surrounded by a wider FLAIR hyperintensity). Early‐onset inflammatory syndrome, and elevated lactate dehydrogenase (LDH) levels were observed in over 90% of cases. Mild and inconsistent meningitis contrasted with a nearly‐constant hyperproteinorachia. An increased interleukin 10/6 ratio over 0,7 was found in 4 of 7 (57%) patients, and skin biopsy led to a pathological diagnosis in 3 of 6 (50%) patients.The results of this study highlight “red flags” that could help accelerate the diagnosis of intravascular lymphoma involving the CNS. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Purpose: Qualitative and quantitative analyses of retinal arteriolar tortuosity in patients with COL4A1 and COL4A2 mutations to identify a tortuosity index (TI) threshold for detecting increased retinal arteriolar tortuosity., Methods: Fifty-two eyes of 28 patients were included. Group 1 included eyes with a normal arteriolar pattern (n = 19, 37%), Group 2 included eyes with moderately increased arteriolar tortuosity (n = 13, 25%), and Group 3 included eyes with typical abnormal arteriolar tortuosity (n = 20, 38%). The TI was measured by calculating the arc-to-chord ratio of arterioles and venules in the posterior pole., Results: The mean arteriolar TI was significantly higher in all groups with a COL4A1/A2 mutation compared with controls: 1.19 ± 0.03, 1.24 ± 0.05, and 1.57 ± 0.23 in Groups 1, 2 and 3, respectively, versus 1.12 ± 0.01 (all P < 0.0001). The TI threshold was 1.13, with a sensitivity of 98.1% and a specificity of 100%. The area under the curve was 0.995., Conclusion: Measuring the arteriolar TI allowed diagnosing increased retinal arteriolar tortuosity in all eyes with a COL4A1 / A2 mutation, whereas the subjective assessment suspected or detected it in only 62% of eyes. In adult patients with cerebral microangiopathy, detecting increased retinal arteriolar tortuosity, even when mild, directs the diagnosis toward COL4A1/A2 -related cerebroretinal angiopathy.

Background: Children with untreated biotinidase deficiency can experience variable symptoms depending on their age of presentation. Older children and adolescents can exhibit predominant neurological deficits including para- or tetraparesis and vision loss., Methods: We report the first case of delayed-onset biotinidase deficiency in a young adult., Results: A 22-year-old man presented with a disabling extensive myelopathy and bilateral optic neuropathy which mimicked the findings of a (seronegative) neuromyelitis optica. Imaging investigations were characterized by an MRI T2 hyper-intensity involving the spinal cord, the optic nerves, the fornix and the mammillar bodies, together with an increased (18)F-FDG uptake on positron emission tomography. He was ultimately shown to have profound biotinidase deficiency due to a novel missense mutation and was partly improved by oral biotin therapy., Conclusion: This individual exemplifies the need to include biotinidase deficiency in the differential diagnosis of patients with extensive myelopathy and/or bilateral optic neuropathy and argues for newborn screening for the disorder., (© The Author(s), 2015.)