pattismith
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I suspect most of us have autonomic failure and CAN with Small Fiber Neuropathy
How to know if you have it?
CAN is diagnosed by the standardised cardiovascular autonomic reflex function tests (CARTs).
Quantitative Sudomotor Axonal Reflex Test (QSART) and Skin biopsy are used for SFN diagnosis.
"These tests assess the parasympathetic system by evaluating beat-to-beat variations during deep breathing, moving from the supine to the standing position and during the Valsalva maneuver (Vals) .
On the other hand, orthostatic hypotension (OH) and the blood pressure response to Vals mostly evaluate the sympathetic system ."
"Cardiovascular reflex tests that include tilt test, deep breathing and Valsalva maneuver are clinically established tests to evaluate patients with orthostatic intolerance [10-12].
The tilt test can detect syncope, orthostatic hypotension and cerebral hypoperfusion that underlie orthostatic symptoms.
Mechanisms provoked by the tilt are complex and include combinations of autonomic, humoral and cardiovascular responses [13-15].
Valsalva maneuver and deep breathing test are used to further refine the integrity of cardiovascular reflex circuits.
Valsalva maneuver assesses predominantly adrenergic functions [16] while deep breathing test evaluates mainly parasympathetic functions [17].
Small fiber autonomic and sensory neuropathy is a common underlying mechanism of orthostatic intolerance [18-23], and can be further evaluated using the quantitative sudomotor axonal reflex test (QSART) [10-12] and skin punch biopsies for assessment of small fibers [24-28].
Cardiovascular reflex and sensory small fiber testing
Our testing protocol used established standards [10,35,36] and was been previously described [36]. Cardiovascular tests included deep breathing, Valsalva maneuver and tilt test.
Sudomotor functions were assessed by the QSART. Signals were recorded using LabChart 7 system (ADInstruments, Inc. Colorado Springs, CO) and sampled at 400 Hz and included electrocardiogram (ECG), blood pressure, respiratory movement using a nasal thermistor, end tidal CO2, and blood flow velocity in the middle cerebral artery using Transcranial Doppler.
RESULTS
Data from 612 patients were included in the analysis. The following diagnostic groups were represented: diabetes mellitus (n,age ± sd,f/m) (92, 61.6 ± 12.6, 42/50), Parkinson disease (88, 70.9 ± 10.8,36/52) and multiple system atrophy (23, 63.8 ± 11.4,10/13).
The remaining patients (n=409) represent a heterogenous group with history of other disorders (typically with n<15) than mentioned above; these disorders include migraine, hypertension, multiple sclerosis, atypical parkinsonism, coronary artery disease, unexplained dizziness, chronic fatigue syndrome and others.
This study provides strong evidence that sensory and autonomic abnormalities coexist.
Both sensory and sweat gland fiber densities were reduced in small fiber neuropathies. The reduction of both types of fibers was disease dependent, being highest in diabetes followed by Parkinson disease.
Furthermore, the fibers reduction was proportional to the severity of autonomic failure.
Therefore inclusion of epidermal sensory and sweat gland fiber density evaluation enables more detailed grading of the severity of small fiber neuropathies and also helps to localize the lesion.
Low correlation of QSART with either epidermal or sweat gland fibers calls for caution when interpreting the QSART results. QSART might overestimate the sudomotor deficit [51] and retest reliability of the QSART is also limited [52,53].This study suggest that sweat gland fiber density might be used as an alternative to QSART.
MORE DETAILS ABOUT METHOD
Deep breathing test was performed at the rate of 6 breaths per minute for 1 minute. Valsalva maneuver was performed in the supine position with an expiratory pressure equal to 40 mm Hg for 15 seconds. Participants were allowed to rest for 10 minutes in supine position and were then tilted to the upright position at 70 degrees for at least 10 minutes if tolerated. QSART was performed using the Q-Sweat machine (WR Medical Electronics, Stillwater, MN) at regional limb temperature above 29.9°C with the simulation current 2 mA for 5 minutes, and the sweat volume was collected for 10 minutes. Baseline supine blood pressure was obtained intermittently using an automated blood pressure device Dinamap ProCare Monitor 100 (GE, Fairfield, CT) and continuously (beat-to-beat) using Finometer® (Finapress Medical Systems, Amsterdam, Netherlands). During the tilt test, the blood pressure was obtained every minute using the Dinamap ProCare and continuously using Finometer®. Normative data for deep breathing test, blood pressure response to the Valsalva maneuver and tilt test, adjusted for age and sex if appropriate, were published previously [10,27,28,36]. The temporal acoustic window with a 2 MHz Transcranial Doppler probe was used for acquisition of blood flow velocity signals using a MultiDop T (DWL, Singen, Germany).
For the Valsalva maneuver, normal response is defined as systolic blood flow velocity ≥85% of the baseline at the end of the phase 2. Epidermal sensory fiber density (ENFD) and sweat gland fiber density (SGFD) were obtained using 3-mm full-thickness skin punch biopsies taken from the lateral thigh (20 cm distal to the iliac spine) and distal leg (10 cm above the lateral malleolus) and stained with PGP 9.5 antibody [23-26]. The samples were processed at Therapath (New York, NY).
The normal values for both ENFD and SGFD were determined by Therapath. The limits of normality for ENFD (5th percentile) at the thigh were 6.2/8.3 (men/women) fibers per millimeter of epidermal length.
https://www.hindawi.com/journals/ije/2018/5607208/
https://www.omicsonline.org/open-ac...iopsies-qasat-2329-6895-1000226.php?aid=50516
How to know if you have it?
CAN is diagnosed by the standardised cardiovascular autonomic reflex function tests (CARTs).
Quantitative Sudomotor Axonal Reflex Test (QSART) and Skin biopsy are used for SFN diagnosis.
"These tests assess the parasympathetic system by evaluating beat-to-beat variations during deep breathing, moving from the supine to the standing position and during the Valsalva maneuver (Vals) .
On the other hand, orthostatic hypotension (OH) and the blood pressure response to Vals mostly evaluate the sympathetic system ."
"Cardiovascular reflex tests that include tilt test, deep breathing and Valsalva maneuver are clinically established tests to evaluate patients with orthostatic intolerance [10-12].
The tilt test can detect syncope, orthostatic hypotension and cerebral hypoperfusion that underlie orthostatic symptoms.
Mechanisms provoked by the tilt are complex and include combinations of autonomic, humoral and cardiovascular responses [13-15].
Valsalva maneuver and deep breathing test are used to further refine the integrity of cardiovascular reflex circuits.
Valsalva maneuver assesses predominantly adrenergic functions [16] while deep breathing test evaluates mainly parasympathetic functions [17].
Small fiber autonomic and sensory neuropathy is a common underlying mechanism of orthostatic intolerance [18-23], and can be further evaluated using the quantitative sudomotor axonal reflex test (QSART) [10-12] and skin punch biopsies for assessment of small fibers [24-28].
Cardiovascular reflex and sensory small fiber testing
Our testing protocol used established standards [10,35,36] and was been previously described [36]. Cardiovascular tests included deep breathing, Valsalva maneuver and tilt test.
Sudomotor functions were assessed by the QSART. Signals were recorded using LabChart 7 system (ADInstruments, Inc. Colorado Springs, CO) and sampled at 400 Hz and included electrocardiogram (ECG), blood pressure, respiratory movement using a nasal thermistor, end tidal CO2, and blood flow velocity in the middle cerebral artery using Transcranial Doppler.
RESULTS
Data from 612 patients were included in the analysis. The following diagnostic groups were represented: diabetes mellitus (n,age ± sd,f/m) (92, 61.6 ± 12.6, 42/50), Parkinson disease (88, 70.9 ± 10.8,36/52) and multiple system atrophy (23, 63.8 ± 11.4,10/13).
The remaining patients (n=409) represent a heterogenous group with history of other disorders (typically with n<15) than mentioned above; these disorders include migraine, hypertension, multiple sclerosis, atypical parkinsonism, coronary artery disease, unexplained dizziness, chronic fatigue syndrome and others.
This study provides strong evidence that sensory and autonomic abnormalities coexist.
Both sensory and sweat gland fiber densities were reduced in small fiber neuropathies. The reduction of both types of fibers was disease dependent, being highest in diabetes followed by Parkinson disease.
Furthermore, the fibers reduction was proportional to the severity of autonomic failure.
Therefore inclusion of epidermal sensory and sweat gland fiber density evaluation enables more detailed grading of the severity of small fiber neuropathies and also helps to localize the lesion.
Low correlation of QSART with either epidermal or sweat gland fibers calls for caution when interpreting the QSART results. QSART might overestimate the sudomotor deficit [51] and retest reliability of the QSART is also limited [52,53].This study suggest that sweat gland fiber density might be used as an alternative to QSART.
MORE DETAILS ABOUT METHOD
Deep breathing test was performed at the rate of 6 breaths per minute for 1 minute. Valsalva maneuver was performed in the supine position with an expiratory pressure equal to 40 mm Hg for 15 seconds. Participants were allowed to rest for 10 minutes in supine position and were then tilted to the upright position at 70 degrees for at least 10 minutes if tolerated. QSART was performed using the Q-Sweat machine (WR Medical Electronics, Stillwater, MN) at regional limb temperature above 29.9°C with the simulation current 2 mA for 5 minutes, and the sweat volume was collected for 10 minutes. Baseline supine blood pressure was obtained intermittently using an automated blood pressure device Dinamap ProCare Monitor 100 (GE, Fairfield, CT) and continuously (beat-to-beat) using Finometer® (Finapress Medical Systems, Amsterdam, Netherlands). During the tilt test, the blood pressure was obtained every minute using the Dinamap ProCare and continuously using Finometer®. Normative data for deep breathing test, blood pressure response to the Valsalva maneuver and tilt test, adjusted for age and sex if appropriate, were published previously [10,27,28,36]. The temporal acoustic window with a 2 MHz Transcranial Doppler probe was used for acquisition of blood flow velocity signals using a MultiDop T (DWL, Singen, Germany).
For the Valsalva maneuver, normal response is defined as systolic blood flow velocity ≥85% of the baseline at the end of the phase 2. Epidermal sensory fiber density (ENFD) and sweat gland fiber density (SGFD) were obtained using 3-mm full-thickness skin punch biopsies taken from the lateral thigh (20 cm distal to the iliac spine) and distal leg (10 cm above the lateral malleolus) and stained with PGP 9.5 antibody [23-26]. The samples were processed at Therapath (New York, NY).
The normal values for both ENFD and SGFD were determined by Therapath. The limits of normality for ENFD (5th percentile) at the thigh were 6.2/8.3 (men/women) fibers per millimeter of epidermal length.
https://www.hindawi.com/journals/ije/2018/5607208/
https://www.omicsonline.org/open-ac...iopsies-qasat-2329-6895-1000226.php?aid=50516
