30 Autonomic function tests To diagnose autonomic peripheral neuropathy, parasympathetic tests (cardiovagal), sympathetic adrenergic tests (cardiovagal), parasympathetic/sympathetic reflex tests (bladder function and pupillometry), sympathetic cholinergic tests (sudomotor) and sympathetic noradrenergic tests are distinguished.103 Cardiovagal tests Cardiovascular autonomic neuropathy (CAN) often remains undiagnosed and is observed in diabetic patients.104 CAN is divided into three categories 1) possible or early CAN confirmed with one abnormal cardiovagal test, 2) definite CAN with at least two abnormal cardiovagal tests and 3) severe CAN with orthostatic hypotension in addition to definite CAN.105 The Ewing’s battery of CAN tests consists of 6 tests 1) heart-rate (HR) response to a Valsalva maneuver, 2) HR response to postural change, 3) HR response to deep breathing, 4) blood pressure (BP) response to a Valsalva maneuver 5) BP response to postural change and 6) BP response to sustained handgrip.106 Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy include the use of the Ewan test, except for the BP response to sustained handgrip.105 Other cardiovagal tests include 7) cold pressor and mental stress test and MIBG-scintigraphy. Parasympathetic test HR response to a Valsalva maneuver: The Valsalva maneuver consists of voluntary forced expiratory effort against closed airways (for example blowing to the volar side of your hand). Increased thoracic pressure results into a decreased preload, provoking a complex autonomic reflex to compensate for arterial pressure loss. Heart activity is measured with an electrocardiogram (ECG) and RR-intervals are used to determine HR-variability. The maneuver consists of 5 different phases; phase (0) deep inspiration, phase (I) onset of strain, phase (II) continued strain, phase (III) release, phase (IV) recovery.107 The Valsalva ratio is calculated by dividing the shortest RR-interval in phase II, with the longest in phase IV.108 Individuals who suffer from SFN, show a lack of bradycardia reflex during phase IV and show a decreased Valsalva ratio.109 HR response to postural change: Changing from supine to upright position results in movement of blood volume from the central- to the peripheral compartment. An abrupt increase in heart rate is important to maintain homeostasis. The sympathetic system, parasympathetic system and baroreflex together remain homeostasis. The “30:15” ratio assesses the HR response to postural change, by dividing the bradycardia after approximately 30 s with the increased HR after approximately 15 s after postural change. In healthy individuals, HR increases with 10 beats/minute. When autonomic failure occurs due to SFN, there will be no bradycardia.110 HR response to deep respiration: In order to measure the HR variability with deep respiration, the amplitude of individual heart beats on an ECG is most commonly used as measure. Mean square successive difference, mean circular resultant, standard deviation of the RR-interval and expiratoryinspiratory ratio can be used as additional measures. The HR variability assesses the vagus nerve function and is confounded by respiratory frequency and tidal volume, age, hypocapnia and increased sympathetic flow.104,108 The vagus nerve is an autonomic nerve fiber and its function might be impaired due to SFN. 2 32 2
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