Long-term mortality is increased after mild traumatic brain injury (mTBI). Central cardiovascular-autonomic dysregulation resulting from subtle, trauma-induced brain lesions might contribute to cardiovascular events and fatalities. We investigated whether there is cardiovascular-autonomic dysregulation after mTBI. In 20 mTBI patients (37±13 years, 5-43 months post-injury) and 20 healthy persons (26±9 years), we monitored respiration, RR intervals (RRI), blood pressures (BP), while supine and upon standing. We calculated the root mean square successive RRI differences (RMSSD) reflecting cardiovagal modulation, the ratio of maximal and minimal RRIs around the 30th and 15th RRI upon standing (30:15 ratio) reflecting baroreflex sensitivity (BRS), spectral powers of parasympathetic high-frequency (HF: 0.15-0.5 Hz) RRI oscillations, of mainly sympathetic low-frequency (LF: 0.04-0.15 Hz) RRI oscillations, of sympathetic LF-BP oscillations, RRI-LF/HF-ratios reflecting sympathovagal balance, and the gain between BP and RRI oscillations as additional BRS index (BRS(gain)). We compared supine and standing parameters of patients and controls (repeated measures analysis of variance; significance: p<0.05). While supine, patients had lower RRIs (874.2±157.8 vs. 1024.3±165.4 ms), RMSSDs (30.1±23.6 vs. 56.3±31.4 ms), RRI-HF powers (298.1±309.8 vs. 1507.2±1591.4 ms(2)), and BRS(gain) (8.1±4.4 vs. 12.5±8.1 ms·mmHg(-1)), but higher RRI-LF/HF-ratios (3.0±1.9 vs. 1.2±0.7) than controls. Upon standing, RMSSDs and RRI-HF-powers decreased significantly in controls, but not in patients; patients had lower RRI-30:15-ratios (1.3±0.3 vs. 1.6±0.3) and RRI-LF-powers (2450.0±2110.3 vs. 4805.9±3453.5 ms(2)) than controls. While supine, mTBI patients had reduced cardiovagal modulation and BRS. Upon standing, their BRS was still reduced, and patients did not withdraw parasympathetic or augment sympathetic modulation adequately. Impaired autonomic modulation probably contributes to cardiovascular irregularities post-mTBI.
Increasing stroke severity was associated with progressive loss of overall autonomic modulation, decline in parasympathetic tone, and baroreflex sensitivity, as well as progressive shift toward sympathetic dominance. All autonomic changes put patients with more severe stroke at increasing risk of cardiovascular complications and poor outcome. NIHSS scores are suited to predict risk of autonomic dysregulation and can be used as premonitory signs of autonomic failure.
Fabry disease is an X-linked recessive disease with a reduction of lysosomal alpha galactosidase A and consecutive storage of glycolipids e.g., in the brain, kidney, skin, and nerve fibers. Cardinal neurologic findings are hypohidrosis, painful episodes, and peripheral neuropathy. So far, the neurophysiological findings regarding the extent of large and small fiber dysfunction are contradictory. This study evaluated large and small nerve fiber function in a homogeneous group of Fabry patients. In 24 of 30 Fabry patients with creatinine below 194.7 mmol/L the authors assessed median, ulnar, and peroneal motor conduction velocity (MCV) and median, ulnar, and sural sensory conduction velocity (SCV) nerve conduction to study the function of thickly myelinated nerve fibers. In addition, the authors studied sympathetic skin responses (SSR) at both hands and feet in 24 patients. To evaluate A beta nerve fiber function, the authors determined vibratory detection thresholds (VDT) at the first toe in 30 patients. Function of A delta and C fibers was assessed by quantitative sensory testing of cold detection threshold (CDT) and heat-pain detection thresholds (HPDT). Nerve conduction studies showed significantly decreased amplitudes of MCVs and SCVs in Fabry patients as compared to controls. However, individual results of MCV and SCV studies were only mildly impaired. SSRs were present in all tested patients but SSR amplitudes were significantly decreased in Fabry patients in comparison to controls. VDT, CDT, and HPDT were significantly elevated in Fabry patients as compared to controls. However, only six patients had pathologic VDT, 19 had increased CDT, and 25 had elevated HPDT at a high level of stimulation. In Fabry patients, small fiber dysfunction is more prominent than large fiber dysfunction, confirming previous findings of sural nerve biopsies. The results suggest a higher vulnerability of small-diameter nerve fibers than of the thickly myelinated fibers.
ERT therapy with agalsidase beta significantly improves function of C-, Adelta-, and Abeta-nerve fibers and intradermal vibration receptors in Fabry neuropathy. Lack of recovery in some patients with abnormal cold or heat-pain perception suggests the need for early ERT, prior to irreversible nerve fiber loss.
. Dynamic cerebral autoregulation remains stable during physical challenge in healthy persons. Am J Physiol Heart Circ Physiol 285: H1048-H1054, 2003; 10.1152/ajpheart.00062.2003.-The effects of physical activity on cerebral blood flow (CBF) and cerebral autoregulation (CA) have not yet been fully evaluated. There is controversy as to whether increasing heart rate (HR), blood pressure (BP), and sympathetic and metabolic activity with altered levels of CO2 might compromise CBF and CA. To evaluate these effects, we studied middle cerebral artery blood flow velocity (CBFV) and CA in 40 healthy young adults at rest and during increasing levels of physical exercise. We continuously monitored HR, BP, endexpiratory CO 2, and CBFV with transcranial Doppler sonography at rest and during stepwise ergometric challenge at 50, 100, and 150 W. The modulation of BP and CBFV in the low-frequency (LF) range (0.04-0.14 Hz) was calculated with an autoregression algorithm. CA was evaluated by calculating the phase shift angle and gain between BP and CBFV oscillations in the LF range. The LF BP-CBFV gain was then normalized by conductance. Cerebrovascular resistance (CVR) was calculated as mean BP adjusted to brain level divided by mean CBFV. HR, BP, CO 2, and CBFV increased significantly with exercise. Phase shift angle, absolute and normalized LF BP-CBFV gain, and CVR, however, remained stable. Stable phase shift, LF BP-CBFV gain, and CVR demonstrate that progressive physical exercise does not alter CA despite increasing HR, BP, and CO 2. CA seems to compensate for the hemodynamic effects and increasing CO2 levels during exercise.cross-spectral analysis; low-frequency blood pressure-cerebral blood flow velocity gain; phase shift angle; cerebrovascular resistance CEREBRAL AUTOREGULATION normally ensures that cerebral blood flow (CBF) remains relatively constant despite fluctuations in blood pressure (BP), provided that mean BP remains within the range of autoregulation, usually from 50 to 170 mmHg (6,21,37). If BP exceeds these limits, CBF increases, initially in a curvilinear relation, and then follows BP passively in a linear relation (21, 31). During increasing levels of physical effort, cerebral perfusion is not only driven by increasing BP and heart rate (HR) but also has to adjust to high levels of sympathetic activity and to altered metabolism with changes in PO 2 and PCO 2 . With increasing muscle metabolism, PO 2 in the blood decreases, whereas PCO 2 increases, unless augmented respiration compensates for the higher O 2 demand and production of CO 2 (17,35,54). Cerebral autoregulation has to counterbalance all the cardiovascular and metabolic responses to physical effort. Although some studies suggest that CBF velocity (CBFV) and CBF remain stable despite physical effort (15), several others found an increase in CBFV (14, 17, 30) as well as regional CBF (10, 55) and global CBF during exercise (24, 51).During cardiovascular changes as they occur with increasing physical challenge, cerebral autoregulation can be evaluated b...
In Fabry disease, there is glycosphingolipid storage in vascular endothelial and smooth muscle cells and neurons of the autonomic nervous system. Vascular or autonomic dysfunction is likely to compromise cerebral blood flow velocities and cerebral autoregulation. This study was performed to evaluate cerebral blood flow velocities and cerebral autoregulation in Fabry patients. In 22 Fabry patients and 24 controls, we monitored resting respiratory frequency, electrocardiographic RR-intervals, blood pressure, and cerebral blood flow velocities (CBFV) in the middle cerebral artery using transcranial Doppler sonography. We assessed the Resistance Index, Pulsatility Index, Cerebrovascular Resistance, and spectral powers of oscillations in RR-intervals, mean blood pressure and mean CBFV in the high (0.15-0.5 Hz) and sympathetically mediated low frequency (0.04-0.15 Hz) ranges using autoregressive analysis. Cerebral autoregulation was determined from the transfer function gain between the low frequency oscillations in mean blood pressure and mean CBFV. Mean CBFV (P < 0.05) and the powers of mean blood pressure (P < 0.01) and mean CBFV oscillations (P < 0.05) in the low frequency range were lower,while RR-intervals, Resistance Index (P < 0.01), Pulsatility Index, Cerebrovascular Resistance (P < 0.05), and the transfer function gain between low frequency oscillations in mean blood pressure and mean CBFV (P < 0.01) were higher in patients than in controls. Mean blood pressure, respiratory frequency and spectral powers of RR-intervals did not differ between the two groups (P > 0.05). The decrease of CBFV might result from downstream stenoses of resistance vessels and dilatation of the insonated segment of the middle cerebral artery due to reduced sympathetic tone and vessel wall pathology with decreased elasticity. The augmented gain between blood pressure and CBFV oscillations indicates inability to dampen blood pressure fluctuations by cerebral autoregulation. Both, reduced CBFV and impaired cerebral autoregulation, are likely to be involved in the increased risk of stroke in patients with Fabry disease.
The pathophysiology of burning mouth syndrome (BMS) is largely unknown. Thus, the aim was to study oral mucosal blood flow in BMS-patients using laser Doppler flowmetry (LDF). Thirteen BMS patients (11 female, two male; mean age+/-SD 64.3+/-7.9 years, mean disease duration 18.9+/-6.2 months) and 13 healthy non-smoking controls matched for age and gender (11 female, two male; mean age 64.7+/-8.1 years) were investigated. Using the LDF technique mucosal blood flow (mBF) was measured at the hard palate, the tip of the tongue, on the midline of the oral vestibule, and on the lip. Measurements were made at rest and over 2 min following dry ice application of 10 s duration using a pencil shaped apparatus. In addition, blood pressure (BP), heart rate (HR), peripheral cutaneous blood flow, and transcutaneous pCO(2) were continuously recorded. Mucosal blood flow (mBF) increased at all measurement sites in response to dry ice application (P<0.001) with peak flow at 0.5--1.5 min after stimulation onset. During the following 1.5--2 min, blood flow decreased at all sites with a tendency to return to baseline towards the end of the observation period. Except for BP and peripheral blood flow, all of the cardiovascular changes exhibited significant changes during the observation period; no differences between groups were detected. When compared to healthy controls BMS patients generally exhibited larger changes in mBF. These changes were significant for recordings made on the hard palate (F[1,24]=13.9, P<0.001). Dry ice stimulation appears to be an effective, non-invasive and reasonably tolerable means to investigate mucosal blood flow at different mucosal sites. In general, vasoreactivity in BMS patients was higher than in healthy controls. BMS patients exhibited a higher response on the hard palate compared to controls. These changes in oral blood flow appear to be specifically related to BMS symptoms indicating a disturbed vasoreactivity.
■ Abstract Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension, we evaluated the effectiveness of countermaneuvers in FD patients.In 17 FD patients (26.4 ± 12.4 years, eight female), we monitored heart rate (HR), blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume while supine, during standing and during application of four countermaneuvers: bending forward, squatting, leg crossing, and abdominal compression using an inflatable belt. Countermaneuvers were initiated after standing up, when systolic BP had fallen by 40 mmHg or diastolic BP by 30 mmHg or presyncope had occurred.During active standing, blood pressure and TPR decreased, calf volume increased but CO remained stable. Mean BP increased significantly during bending forward (by 20.0 (17-28.5) mmHg; P = 0.005) (median (25 th -75 th quartile)), squatting (by 50.8 (33.5-56) mmHg; P = 0.002), and abdominal compression (by 5.8 (-1-34.7) mmHg; P = 0.04) -but not during leg-crossing. Squatting and abdominal compression also induced a significant increase in CO (by 18.1 (-1.3-47.9) % during squatting (P = 0.02) and by 7.6 (0.4-19.6) % during abdominal compression (P = 0.014)). HR did not change significantly during the countermaneuvers. TPR increased significantly only during squatting (by 37.2 (11.8-48.2) %; P = 0.01). However, orthopedic problems or ataxia prevented several patients from performing some of the countermaneuvers. Additionally, many patients required assistance with the maneuvers.Squatting, bending forward and abdominal compression can improve orthostatic BP in FD patients, which is achieved mainly by an increased cardiac output. Squatting has the greatest effect on orthostatic blood pressure in FD patients. Suitability and effectiveness of a specific countermaneuver depends on the orthopedic or neurological complications of each FD patient and must be individually tested before a therapeutic recommendation can be given.■ Key words physical maneuvers · familial dysautonomia · syncope · autonomic failure · impedance cardiography 1 Published in "Journal of Neurology 253(1): 65-72, 2006" which should be cited to refer to this work.
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