The Glymphatic System: A Review

The brain represents 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glialdependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.

The Natural History of Brain Arteriovenous Malformations

Brain arteriovenous malformations (AVMs) are relatively rare lesions with irreversible consequences in the context of hemorrhage. They are characterized by direct connections between arteries and veins without an intervening capillary network. The natural history of brain AVMs is controversial in the literature, with low evidence level gathered in the papers published, and with large divergence of results among them. A detailed understanding of the natural history is critical for treatment decision. The risk of development of deleterious outcomes such as hemorrhage or brain infarction should always be considered when submitting a patient to the risks of treatment. Several factors related to the patient and to the AVMs are determinants in the natural history of this disease. The topography, size, morphology and angioarchitecture of AVMs determine the risk of rupture. Large AVMs, those located in the posterior fossa and with deep venous drainage, have higher risk of rupture. Due to divergence in the literature regarding the natural history of AVMs, the choice of treatment should also consider experiences acquired over the years from reference centers with a high number of AVMs treated per year. We determined 7 variables that should be considered during the decision to treat an AVM: 1) previous hemorrhage; 2) aneurysm associated to the AVM; 3) direct arteriovenous fistula; 4) factors related to the nidus; 5) age and habits (smoking, sedentary lifestyle, diet quality); 6) the functional performance of the patient; 7) psychological factors.

Malformações arteriovenosas (MAVs) são lesões caracterizadas por conexões diretas entre artérias e veias sem rede capilar. São relativamente raras e com consequências muitas vezes irreversíveis no contexto de hemorragia. A história natural das MAVs é controversa na literatura, com pouca evidência extraída dos artigos publicados, além de alta divergência entre resultados. Um entendimento detalhado da história natural da doença é determinante para a decisão do tratamento. O risco de desenvolver consequências deletérias como hemorragia ou isquemia deve ser sempre considerado antes de submeter pacientes ao tratamento. Vários fatores relacionados ao paciente e às MAVs são determinantes na história natural da doença. A localização, tamanho, morfologia e angioarquitetura das MAVs estimam o risco de ruptura. As MAVs grandes, de fossa posterior, com drenagem venosa profunda, têm maior risco de ruptura. A decisão de tratar deve também levar em conta a experiência do serviço, adquirida após anos de tratamento de MAVs. Nós determinamos 7 fatores que devem ser avaliados diante da decisão de tratamento das MAVs: 1) hemorragia prévia; 2) aneurismas associados à MAV; 3) fístula arteriovenosa; 4) fatores relacionados ao nidus; 5) idade e hábitos de vida; 6) performance funcional do paciente; 7) fatores psicológicos.

Hemorrhagic intracranial distal (cortical) dissections: five cases and a literature review / Dissecções hemorrágicas intracranianas distais (corticais): cinco casos e revisão da literatura

Objective: To describe and analyze five cases of symptomatic intracranial spontaneous cortical dissections and a review of the literature relating to this disorder. Method: Retrospective analysis of patients undergoing investigation for intracranial hemorrhage. Data were compiled from the medical file and PACS of the Nancy University Hospital. Results: Of 350 patients who underwent investigation for spontaneous intracranial hemorrhage, five patients (four women) harbored intracranial distal dissections, with no evidence of infection, trauma, arterial hypertension, vasculitis. The patients age ranged from 35 to 77 years (mean age 50.8 years). No patient presented with a poor grade SAH (Hunt and Hess grade IV or V). All patients presented with headache. The localization of the vessel abnormality was equally distributed between the anterior and posterior circulation. All patients, except one, harbored an aneurysmal sac angiographically detectable. Conclusion: Dissecting aneurysms of the intracranial distal/cortical arteries are exceedingly rare vascular lesions that produce neurologic symptoms related to their topography and hemorrhagic or ischemic nature. In the aneurysmal forms, the treatment in an urgent fashion may be considered if we consider the risk of re-hemorrhage. The first-choice treatment is coil occlusion of the involved artery at the level of the dissection.

Objetivo: Descrever e analisar 5 casos de dissecção intracraniana de artérias distais espontâneas sintomáticas, com revisão da literatura. Métodos: Análise retrospectiva dos prontuários e imagens de tomografia, ressonância e angiografia. Os dados foram compilados do arquivo de imagens eletrônicas em formato DICOM através do sistema PACS do Hospital Universitário de Nancy, França. Resultados: De 350 pacientes investigados por hemorragia intracraniana espontânea, foram identificados 5 pacientes (4 do sexo feminino) com aneurismas intracranianos distais, onde foram descartadas as etiologias habituais (infecção, trauma, hipertensão arterial, vasculite). A média de idade foi de 50,8 anos, com mínima de 35 e máxima de 77 anos. Nenhum paciente estava com hemorragica de alto grau (Hunt-Hess grau 4 ou 5). Todos tiveram cefaléia súbita como sintoma inicial. A localização da anormalidade vascular foi igualmente distribuida entre a circulação anterior e posterior. Todos os pacientes, exceto um, apresentavam aneurisma angiograficamente detectável. Conclusão: Pequenas hemorragias intracranianas em vasos corticais são frequentemente encontradas, mas raramente investigadas. Aneurismas dissecantes das artérias distais/corticais são lesões extremamente raras que produzem sintomas relacionados a sua topografia e natureza isquêmica ou hemorrágica. A história natural destas lesões é pouco conhecida ou documentada. Aneurismas devem ser ocluidos preferencialmente com micromolas, evitando ressangramento.