Excessive Daytime Sleepiness Is a Common Symptom in Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficient activity of the enzyme α-galactosidase A, resulting in a vasculopathic involvement of various organ systems, e.g. cerebral structures. Marked cerebral vasculopathy with subsequent white matter lesions (WML) are a frequent finding in FD patients. Recent studies discussed an association between cerebral white matter changes and sleep-related disturbances of breathing, which may lead to excessive daytime sleepiness (EDS). A 56-year-old Caucasian female FD patient with EDS was admitted to our sleep laboratory. Overnight polysomnography showed a Cheyne-Stokes respiration pattern with significant O(2) desaturation. MR imaging revealed confluent WML including the brain stem, but no renal or cardiac involvement. We then evaluated the clinical data of 49 genetically proven FD patients (27 males; mean age 43 years) from our FD centre. With a frequency of 68%, EDS exceeds the prevalence of other common symptoms of FD (angiokeratomas 61%; acroparaesthesia 51%; renal involvement 29%; cardiac involvement 27%), and the prevalence of chronic fatigue (48%). EDS was independently associated with the physical component summary of the SF-36 data (corrected R(2) = -0.323, p < 0.001). EDS and age explained a quarter of variance in mental component summary (corrected R(2) = -0.253, p < 0.001). We conclude that EDS is a common and underdiagnosed symptom in FD patients, accompanied by a significant impact on quality of life. EDS might be caused by central breathing disorders due to an affection of brain regions associated with respiratory control in FD.

Night-time bradyarrhythmia in a patient with mild obstructive sleep apnea syndrome is reversed with CPAP treatment.

Nocturnal cardiac arrhythmia is a common clinical feature of obstructive sleep apnea syndrome. Pathologically relevant rhythm disturbances such as atrioventricular block or ventricular tachycardia are known to occur mainly in patients with a high apnea-hypopnea index and marked oxygen desaturation. We report on a patient with mild obstructive sleep apnea syndrome who nevertheless showed intermittent second-degree atrioventricular block during stages of rapid eye movement sleep-associated hypopneas. Cardiac arrhythmia was reversed with the initiation of nasal continuous positive airway pressure treatment. Based on this case report and taking into account known facts from the literature, the finding of intermittent second-degree atrioventricular block in our patient with mild obstructive sleep apnea syndrome supports careful evaluation of electrocardiogram recording acquired during polysomnography in all patients with suspected obstructive sleep apnea syndrome.

Capnography screening for sleep apnea in patients with acute stroke.

Sleep apnea syndrome (SAS) is a prominent clinical feature in acute stroke patients. Diagnosis is usually established by polysomnography or cardio-respiratory polygraphy (CRP). Both diagnostic procedures produce high costs, are dependent on the access to a specialized sleep laboratory, and are poorly tolerated by patients with acute stroke. In this study we therefore investigated whether capnography may work as a simple screening tool in this context. In addition to conventional CRP, 27 patients with acute stroke were studied with capnography provided by our standard monitoring system. The trend graphs of the end-tidal CO(2) values (EtCO(2)) were used to determine the capnography-based estimate of the apnea-hypopnea index (AHI(CO2)). Index events were scored when the EtCO(2) value dropped for > 50% of the previous baseline value. We found that the AHI(CO2) correlated significantly with the apnea-hypopnea index measured with conventional CRP (AHI(CRP)) (r = 0.94; p < 0.001). An AHI(CO2) > 5 turned out to be highly predictive of an AHI(CRP) > 10. According to our findings, routinely acquired capnography may provide a reliable estimate of the AHI(CRP). The equipment needed for this screening procedure is provided by the monitoring systems of most intensive care units and stroke units where stroke patients are regularly treated during the first days of their illness. Therefore, early diagnosis of SAS in these patients is made substantially easier.

Bone marrow-derived cells expressing green fluorescent protein under the control of the glial fibrillary acidic protein promoter do not differentiate into astrocytes in vitro and in vivo.

Differentiation of bone marrow (BM) cells into astroglia expressing the glial fibrillary acidic protein (GFAP) has been reported in vitro and after intracerebral or systemic BM transplantation. In contrast, recent data suggest that astrocytic differentiation does not occur from BM-derived cells in vivo. Using transgenic mice that express the enhanced green fluorescent protein (GFP) under the control of the human glial fibrillary acidic protein (GFAP) promoter, we investigated the potential of adult murine BM-derived cells to differentiate into macroglia. In the brains of GFAP-GFP transgenic mice, astrocytes were brightly fluorescent from the expression of GFP. When BM from these animals was transplanted into lethally irradiated wild-type animals, the transgene was detected in the reconstituted hematopoietic system, but no GFP expression was found in the nervous system. In contrast, GFAP-GFP neuroectodermal anlage grafted into adult wild-type striatum gave rise to GFP-expressing astrocytes. Because cerebral ischemia has been suggested to promote the differentiation of BM-derived cells into astrocytes, BM chimeric mice were subjected to focal cerebral ischemia. No GFP-positive cells were found in the ischemic or contralateral hemispheres of these brains. Even after direct injection of GFAP-GFP transgenic BM cells into wild-type striatum, no GFP-expressing astroglia were detected. To test the hypothesis that the in vitro environment might be more permissible for astroglial differentiation, we cultured BM from mice that constitutively express GFP, BM cells expressing GFP from a retroviral vector, and BM from GFAP-GFP transgenic mice on astrocytes and on organotypic hippocampal slices. In all experimental paradigms, BM-derived cells were found to differentiate into ramified microglia but not into GFAP-expressing astrocytes.