ABSTRACT
Obstructive sleep apnoea (OSA) has previously been described in a large family suffering from Charcot-Marie-Tooth disease type 1 (CMT1). In the present study, we used a case control design to establish whether this suggested link between OSA and CMT1 may also be found when studying genetically non-related patients. 12 patients with CMT1 and 24 control patients matched for age, sex and body mass index (BMI) were included in the study. Neurological disability was graded with a previously established 6 point score. All patients underwent overnight polysomnography. The mean apnoea-hypopnoea index (AHI) of patients with CMT1 was 10.5 (16.3) which was significantly higher than that of the control group (1.5 (1.3)). Five out of 12 patients with CMT1 had an AHI > or =10/h compared with 1 of 24 control patients (p<0.01). In patients with CMT1, a significant correlation between AHI and neurological disability was found (Spearman r = 0.62; p = 0.031) while BMI and age were not related to AHI. CMT1, in particular CMT1A, predisposes with disease progression to the development of OSA. Pathophysiologically, one may assume that CMT1 related pharyngeal neuropathy increases the collapsibility of the upper airway which in turn leads to recurring obstructive respiratory events.
Subject(s)
Charcot-Marie-Tooth Disease/complications , Sleep Apnea, Obstructive/epidemiology , Adult , Age Factors , Body Mass Index , Case-Control Studies , Charcot-Marie-Tooth Disease/physiopathology , Cohort Studies , Female , Humans , Male , Middle Aged , Polysomnography , Risk Factors , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/physiopathologyABSTRACT
Virchow-Robin's perivascular spaces lie between the basement membrane around pericytes and the basement membrane at the surface of the glia limitans of the brain vessels. They are directly connected to the subpial space and harbour a population of cells distinct from pericytes, perivascular microglia and other cells within perivascular spaces (e.g. T cells and mast cells) in their ability to quickly phagocytose particles from the cerebrospinal fluid (CSF). Morphology, function, and cell surface proteins of these perivascular cells suggest an origin from the monocyte/macrophage lineage. It is currently unclear to what extent these brain perivascular cells represent a resident population of histiocytes or undergo continuous supplementation from blood monocytes. Using transplants of green-fluorescent-protein (GFP)-transfected bone marrow cells, we therefore investigated the replacement of perivascular cells by blood-borne macrophages in adult mice. GFP-positive cells in the perivascular spaces were found as early as 2 weeks post transplantation. The substitution of host perivascular cells by donor-derived macrophages was then evaluated using immunocytochemistry and intraventricular injection of hydrophilic rhodamine-fluorescent tracers. Such tracers diffuse along perivascular spaces and are subsequently phagocytosed by perivascular cells leading to stable phagocytosis-dependent labelling. Thus, the population of newly immigrated macrophages could be related to the total number of perivascular macrophages. This approach revealed a continuous increase of donor-derived perivascular cells. At 14 weeks post transplantation, all perivascular cells were donor-derived. These data show that brain perivascular cells are a population of migratory macrophages and not resident histiocytes.
