Mast cell disorders are associated with decreased cerebral blood flow and small fiber neuropathy

Background: Mast cell disorders including hereditary alpha tryptasemia (H alpha T) and idiopathic mast cell activation syndrome (MCAS) can be associated with neurologic symptoms such as orthostatic intolerance, pain, and cognitive impairment. The origin of these symptoms is not well understood. Objective: To characterize neurologic findings in patients with H alpha T and MCAS through objective measurements. Methods: Patients with a confirmed diagnosis of H alpha T or MCAS with neurologic symptoms were referred for standardized autonomic testing encompassing Valsalva maneuver, deep breathing, sudomotor and tilt tests with cerebral blood flow velocity (CBFv) determination, and skin biopsies for small fiber neuropathy (SFN). Results: There were 15 patients with H alpha T (age 44.4 +/- 15.9 years), 16 with MCAS (34.4 +/- 15.5), and 14 matched controls who were evaluated. Baseline serum tryptase level was increased in patients with H alpha T when compared with patients with MCAS (14.3 +/- 2.5 ng/mL vs 3.8 +/- 1.8; P <.001) and neurologic symptoms were similar between the 2 groups. When compared with controls, orthostatic CBFv was reduced in H alpha T (-24.2 +/- 14.3%; P <.001) and MCAS (-20.8 +/- 5.5%; P <.001). Reduced nerve fibers consistent with SFN were found in 80% of patients with H alpha T and 81% of those with MCAS. Mild-to-moderate dysautonomia was detected in all patients with H alpha T and MCAS when results of sympathetic, parasympathetic, and sudomotor tests were combined. Conclusion: We provide evidence of reduced orthostatic CBFv and SFN associated with mild-to-moderate autonomic dysfunction in patients with H alpha T and MCAS. Our findings suggest that comprehensive autonomic testing may be helpful to explain neurologic symptoms and guide treatment in patients with H alpha T and MCAS. (C) 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Automated summary

This study investigates the neurologic findings in patients with H alpha T and MCAS, revealing reduced orthostatic cerebral blood flow velocity and small fiber neuropathy (SFN), along with mild-to-moderate autonomic dysfunction. The findings suggest that comprehensive autonomic testing may be helpful in explaining neurologic symptoms and guiding treatment in patients with H alpha T and MCAS.