Cerebellar impairment during an orthostatic challenge in patients with neurogenic orthostatic hypotension

•Autonomic failure is characterized by severe hypotension during orthostatic challenges.•Patients have significantly less cerebellar activation during baroreflex mediated challenges.•Failure of the vestibulo-sympathetic reflexes may contribute to the pathophysiology of dysautonomia. Compare activation patterns within the cortical autonomic network in patients with neurogenic orthostatic hypotension (NOH) versus healthy age-matched controls during an orthostatic challenge. Fifteen health controls and 15 NOH patients performed 3 Valsalva maneuvers, and 5-min of lower-body negative pressure (LBNP) during a functional brain MRI. Compared to controls, NOH patients had significantly less activation within the cerebellum during both LBNP and VM. Both groups had significant activation of the bilateral insula and left thalamus during LBNP. No significant differences were found during the recovery phase of LBNP. The cerebellum, which plays an important role in vestibulo-sympathetic reflexes, important for blood pressure adjustments during postural changes, appear to be affected in patients with NOH. The cerebellum also appears to be affected during other baroreflex mediated stressors such as the VM. Orthostatic reflexes mediated by the cerebellum may be impaired in patients with NOH. The results suggest an additional pathological pathway in patients with autonomic failure.