Neurological Disorders

Quantitative Scale for Grading of Cardiovascular Autonomic Reflex Tests and Small Fibers from Skin Biopsies (QASAT)

Abstract

Peter Novak

Background: Orthostatic intolerance including dizziness and syncope is common and may reflect autonomic dysfunction. Cardiovascular reflex tests (deep breathing, Valsalva maneuver and tilt test) are established diagnostic methods for evaluation of orthostatic and autonomic symptoms. Small fiber neuropathy, a frequent underlying mechanism, is evaluated by the quantitative sudomotor axonal reflex test (QSART) and skin biopsies. The comprehensive quantitative scale to grade abnormalities in these tests is lacking.
Methods: This study defines the QASAT - Quantitative scale for grading of cardiovascular reflex tests using heart rate, blood pressure, n transcranial Doppler, QSART and small fibers (intrapidermal sensory and sweat gland) densities from skin biopsies. The QASAT has three main categories: cardiovascular, cerebral blood flow (includes cerebral autoregulation/vasoreactivity score) and small fiber neuropathy. QASAT was validated in 612 participants with diabetes mellitus (92), Parkinson’s disease (88), multiple system atrophy (23) and other diagnoses (409). The QASAT was compared with the Composite Autonomic Severity Score using ANOVA, correlations and sensitivity/specificity analysis.
Results: Scores of heart rate variability from deep breathing, orthostatic hypotension, orthostatic cerebral blood flow, sensory and sweat gland small fiber densities were disease specific (p<0.0001) and were correlated with the severity of autonomic failure (r=0.84, p<0.0001). Autonomic, sensory and cerebral blood flow abnormalities coexist and are correlated. Initial response to slow and fast tilt, baroreflex gain, QT interval, catecholamines and spectral analysis of the heart rate failed to correlate with severity of autonomic failure and therefore were not included in QASAT.
Conclusion: QASAT is an objective and validated instrument for grading of dysautonomia, associated small fiber neuropathy and cerebral blood flow. QASAT quantifies both below (bradycardia, supine/orthostatic hypotension) and above (tachycardia, supine/orthostatic hypertension) normal values. Cardiovascular tests are enhanced by scoring the cerebral hypoperfusion which underlies orthostatic symptoms. Inclusion of epidermal and sweat gland fiber density scoring improves lesion localization.