ABSTRACT
La enfermedad de CADASIL (arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía) es una angiopatía sistémica hereditaria que afecta fundamentalmente a los vasos cerebrales de pequeño y mediano calibre. Alrededor de 500 familias están afectadas en el mundo, la mayoría de ellas en Europa. Se caracteriza por presentar crisis de migraña, demencia subcortical, trastornos neuropsiquiátricos e ictus isquémicos de repetición. Nuestro objetivo ha sido describir por primera vez en la literatura el manejo mediante anestesia general de un procedimiento neuroquirúrgico intracraneal en un paciente con la enfermedad de CADASIL. Consideramos esencial la monitorización continua de la presión arterial, así como el mantenimiento de normocapnia y normotermia para evitar el desarrollo de nuevos accidentes cerebrovasculares. Esta enfermedad resulta relevante debido a sus implicaciones anestésicas y las escasas publicaciones hasta la fecha
CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy) disease is an inherited systemic arterial disease that affects the small and medium calibre cerebral vessels. Around 500 families are affected in the world, most of them in Europe. It is characterised by migraine attacks, subcortical dementia, neuropsychiatric disorders, and recurrent ischaemic strokes. The objective of this article is to describe, for the first time in the literature, the management by general anaesthesia of an intracranial neurosurgical procedure in a patient with CADASIL disease. Continuous monitoring of blood pressure is considered essential, as well as the maintenance of normocapnia and normothermia to avoid the development of new cerebrovascular accidents. This disease is relevant due to its anaesthetic implications and the few publications to date
Subject(s)
Humans , Female , Middle Aged , Anesthesia, General/methods , CADASIL/surgery , Neurosurgical Procedures/methods , Monitoring, Intraoperative/methods , Rare Diseases/surgery , Intracranial Pressure/physiologyABSTRACT
CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy) disease is an inherited systemic arterial disease that affects the small and medium calibre cerebral vessels. Around 500 families are affected in the world, most of them in Europe. It is characterised by migraine attacks, subcortical dementia, neuropsychiatric disorders, and recurrent ischaemic strokes. The objective of this article is to describe, for the first time in the literature, the management by general anaesthesia of an intracranial neurosurgical procedure in a patient with CADASIL disease. Continuous monitoring of blood pressure is considered essential, as well as the maintenance of normocapnia and normothermia to avoid the development of new cerebrovascular accidents. This disease is relevant due to its anaesthetic implications and the few publications to date.
Subject(s)
Anesthesia, General/methods , CADASIL/surgery , Female , Humans , Middle Aged , Monitoring, Intraoperative/methodsABSTRACT
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a Notch3 dominant mutation-induced cerebral small vascular disease, is characterized by progressive degeneration of vascular smooth muscle cells (vSMCs) of small arteries in the brain, leading to recurrent ischemic stroke, vascular dementia and death. To date, no treatment can stop or delay the progression of this disease. Herein, we determined the therapeutic effects of stem cell factor (SCF) in combination with granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in a mouse model of CADASIL carrying the human mutant Notch3 gene. SCF+G-CSF was subcutaneously administered for 5 days and repeated 4 times with 1-4 month intervals. We found through water maze testing that SCF+G-CSF treatment improved cognitive function. SCF+G-CSF also attenuated vSMC degeneration in small arteries, increased cerebral blood vascular density, and inhibited apoptosis in CADASIL mice. We also discovered that loss of cerebral capillary endothelial cells and neural stem cells/neural progenitor cells (NSCs/NPCs) occurred in CADASIL mice. SCF+G-CSF treatment inhibited the CADASIL-induced cell loss in the endothelia and NSCs/NPCs and promoted neurogenesis. In an in vitro model of apoptosis, SCF+G-CSF prevented apoptotic cell death in vSMCs through AKT signaling and by inhibiting caspase-3 activity. These data suggest that SCF+G-CSF restricts the pathological progression of CADASIL. This study offers new insights into developing therapeutic strategies for CADASIL.
