Alterated cerebrovascular reactivity in patients with adult-onset Pompe disease: consequences of vascular smooth muscle involvement?

Aims: Involvement of smooth muscle in blood vessels in late-onset glycogenosis type II (GSDII, Pompe disease), a skeletal muscle disease, suggests a multisystemic disorder. Patients/ Methods: Ten patients with GSDII (8/10 on enzyme replacement therapy, ERT) were screened for pathological glycogen accumulation in smooth muscles of blood vessels (skeletal muscle and skin biopsy), by magnetic resonance angiography (MR-A), transcranial duplex ultrasound and for vascular risk factors. Cerebrovascular reactivity as a function of smooth muscles in the arterioles was tested by changing the CO2 partial pressure. Results: Before ERT the skeletal muscle and skin biopsy showed pathological lysosomal glycogen accumulation in smooth muscles. Functional tests for cerebrovascular reactivity revealed re-duced arteriolar vasodilatation after acetazolamide and decreased arteriolar vasoconstriction during hyperventilation in 3/9 patients. During ERT cerebrovascular reactivity after aceta-zolamide increased. MR-A revealed ectasia/dolichobasilar arteries in 2/10 patients, but no cerebral aneurysm. Conclusion: Although histopathological examination showed involvement of smooth muscles in GSDII patients MR-A revealed no cerebral aneurysms. Smooth muscles in cerebral vessels appeared to be functionally impaired in some patients and improved in all patients during long-time ERT. Electron microscopic examination of the arrector pili muscles appears to be a surrogate marker for the involvement of smooth muscles and might serve as an indicator of therapeutic efficacy.