Julia Koehn

Frequency Analysis Unveils Cardiac Autonomic Dysfunction after Mild Traumatic Brain Injury

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.

Head and Neck Cooling Decreases Tympanic and Skin Temperature, But Significantly Increases Blood Pressure

Background and Purpose— Localized head and neck cooling might be suited to induce therapeutic hypothermia in acute brain injury such as stroke. Safety issues of head and neck cooling are undetermined and may include cardiovascular autonomic side effects that were identified in this study. Methods— Ten healthy men (age 35±13 years) underwent 120 minutes of combined head and neck cooling (Sovika, HVM Medical). Before and after onset of cooling, after 60 and 120 minutes, we determined rectal, tympanic, and forehead skin temperatures, RR intervals, systolic and diastolic blood pressures (BP), laser-Doppler skin blood flow at the index finger and cheek, and spectral powers of mainly sympathetic low-frequency (0.04–0.15 Hz) and parasympathetic high-frequency (0.15–0.5 Hz) RR interval oscillations and sympathetic low-frequency oscillations of BP. We compared values before and during cooling using analysis of variance with post hoc analysis; (significance, P<0.05). Results— Forehead skin temperature dropped by 5.5±2.2°C with cooling onset and by 12.4±3.2°C after 20 minutes. Tympanic temperature decreased by 4.7±0.7°C within 40 minutes, and rectal temperature by only 0.3±0.3°C after 120 minutes. Systolic and diastolic BP increased immediately on cooling onset and rose by 15.3±20.8 mm Hg and 16.5±13.4 mm Hg (P=0.004) after 120 minutes, whereas skin blood flow fell significantly during cooling. RR intervals and parasympathetic RR interval high-frequency powers increased with cooling onset and were significantly higher after 60 and 120 minutes than they were before cooling. Conclusions— Head and neck cooling prominently reduced tympanic temperature and thus might also induce intracerebral hypothermia; however, it did not significantly lower body core temperature. Profound skin temperature decrease induced sympathetically mediated peripheral vasoconstriction and prominent BP increases that are not offset by simultaneous parasympathetic heart rate slowing. Prominent peripheral vasoconstriction and BP increase must be considered as possibly harmful during head and neck cooling.

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

Background In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions. Objectives To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation. Methods Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and “sustained-handgrip-exercise” in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05). Results Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05). Conclusions The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod. Trial Registration German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do

Extracranial internal carotid artery vasospasm due to sympathetic dysfunction

Isolated vasospasms of the extracranial internal carotid artery (ICA) are rare causes of cerebral ischemia.1,2 Pathophysiology of ICA vasospasms is not yet understood and may be associated with altered autonomic ICA innervation. ### Case description. A 25-year-old patient presented with transient right amaurosis and left hemiparesis. Since age 12, he …

Reliability and Limitations of Automated Arrhythmia Detection in Telemetric Monitoring After Stroke

Background and Purpose— Guidelines recommend continuous ECG monitoring in patients with cerebrovascular events. Studies on intensive care units (ICU) demonstrated high sensitivity but high rates of false alarms of monitoring systems resulting in desensitization of medical personnel potentially endangering patient safety. Data on patients with acute stroke are lacking. Methods— One-hundred fifty-one consecutive patients with acute cerebrovascular events were prospectively included. Automatically identified arrhythmia events were analyzed by manual ECG analysis. Muting of alarms was registered. Sensitivity was evaluated by beat-to-beat analysis of the entire recorded ECG data in a subset of patients. Ethics approval was obtained by University of Erlangen-Nuremberg. Results— A total of 4809.5 hours of ECG registration and 22 509 alarms were analyzed. The automated detection algorithm missed no events but the overall rate of false alarms was 27.4%. Only 0.6% of all alarms indicated acute life-threatening events and 91.4% of these alarms were incorrect. Transient muting of acoustic alarms was observed in 20.5% patients. Conclusions— Continuous ECG monitoring using automated arrhythmia detection is highly sensitive in acute stroke. However, high rates of false alarms and alarms without direct therapeutic consequence cause desensitization of personnel. Therefore, acoustic alarms may be limited to life-threatening events but standardized manual evaluation of all alarms should complement automated systems to identify clinically relevant arrhythmias.

Combined counter‐maneuvers accelerate recovery from orthostatic hypotension in familial dysautonomia

In patients with familial dysautonomia (FD), prominent orthostatic hypotension (OH) endangers cerebral perfusion. Supine repositioning or abdominal compression improves systolic and diastolic blood pressure (BPsys and BPdia).

Metronomic breathing shows altered parasympathetic baroreflex function in untreated Fabry patients and baroreflex improvement after enzyme replacement therapy.

Objective In untreated Fabry patients without overt autonomic dysfunction and normal baroreflex sensitivity (BRS) at rest, BRS is impaired during orthostatic, sympathetic challenge but normalizes after enzyme-replacement therapy (ERT) (Hilz et al., J Hypertens 2010; 28:1438–1448). This study evaluated BRS during parasympathetic challenge with six cycles per minute metronomic deep breathing (MDB) in Fabry patients before and after ERT. Methods In 22 Fabry patients (28 ± 8years), we monitored RR-intervals (RRIs), SBP, and respiratory frequency during spontaneous breathing (spont_breath) and MDB, before and after 18 (11 patients) or 23 months (11 patients) of biweekly ERT (1.0 mg/kg agalsidase beta). We determined spectral powers of mainly sympathetic low-frequency (0.04–0.15 Hz) RRI fluctuations, parasympathetic high-frequency (0.15–0.5 Hz) RRI fluctuations, sympathetically mediated low-frequency powers of SBP and high-frequency powers of SBP. We calculated BRS (ms/mmHg) during spont_breath and MDB as low-frequency–high-frequency alpha index (coherence >0.5). We compared parameters during spont_breath and MDB within and between patients before and after ERT and 15 age-matched (27 ± 5years) healthy men (RANOVA and posthoc analysis; significance: P < 0.05). Results During spont_breath and MDB, parameters were similar between groups. Within the three groups, RRIs were lower, whereas RRI low-frequency powers and SBP low-frequency powers were higher during MDB than during spont_breath. BRS was similar during MBD and spont_breath in untreated patients (P > 0.05), but increased significantly with MDB in patients after ERT (P = 0.048) and in controls (P = 0.035). Conclusion In untreated Fabry patients, MDB uncovers impaired BRS. After 18 or 23 months of ERT, MDB-induced BRS increase is similar in Fabry patients and controls, demonstrating that ERT not only restores sympathetic but also parasympathetic baroreflex activation.

Autonomic Blockade During Sinusoidal Baroreflex Activation Proves Sympathetic Modulation of Cerebral Blood Flow Velocity

Background and Purpose— Pharmacological blockade showed sympathetic origin of 0.03 to 0.15 Hz blood pressure (BP) oscillations and parasympathetic origin of 0.15 to 0.5 Hz RR-interval (RRI) oscillations, but has not been used to determine origin of cerebral blood flow velocity (CBFV) oscillations at these frequencies. This study evaluated by pharmacological blockade whether 0.1 Hz CBFV oscillations are related to sympathetic and 0.2 Hz CBFV oscillations to parasympathetic modulation. Methods— In 11 volunteers (24.6±2.3 years), we monitored RRIs, BP, and proximal middle cerebral artery CBFV, at rest, during 180 s sympathetic BP activation by 0.1 Hz sinusoidal neck suction (NS), and during 180 s parasympathetic RRI activation by 0.2 Hz NS. We repeated recordings after 25 mg carvedilol, and after 0.04 mg/kg atropine. Autoregressive analysis quantified RRI-, BP-, and CBFV-spectral powers at 0.1 Hz and 0.2 Hz. We compared parameters at rest, during 0.1 Hz, or 0.2 Hz NS, with and without carvedilol or atropine (analysis of variance, post hoc testing; significance, P<0.05). Results— Carvedilol significantly increased RRIs and lowered BP, CBFV, and 0.1 Hz RRI-, BP-, and CBFV-powers at baseline (P=0.041 for CBFV-powers), and during 0.1 Hz NS-induced sympathetic activation (P<0.05). At baseline and during 0.2 Hz NS-induced parasympathetic activation, atropine lowered RRIs and 0.2 Hz RRI-powers, but did not change BP, CBFV, and 0.2 Hz BP- and CBFV-powers. Conclusions— Attenuation of both 0.1 Hz CBFV and BP oscillations after carvedilol indicates a direct relation between 0.1 Hz CBFV oscillations and sympathetic modulation. Absent effects of atropine on BP, CBFV, and 0.2 Hz BP and CBFV oscillations suggest that there is no direct parasympathetic influence on 0.2 Hz BP and CBFV modulation.

Eyeball pressure stimulation induces subtle sympathetic activation in patients with a history of moderate or severe traumatic brain injury

OBJECTIVE After traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation. METHODS In 51 post-moderate-severe-TBI patients (32.7 ± 10.5 years old, 43.1 ± 33.4 months post-injury), and 30 controls (29.1 ± 9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05). RESULTS At rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter. CONCLUSIONS In post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation. SIGNIFICANCE Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI.

Can stapedius reflex testing objectively measure muscle function in Pompe patients

We assessed the value of stapedius reflex testing as an objective measurement of striated muscle function in four patients with Pompe disease. Common tests of disease severity and efficacy of enzyme replacement therapy (ERT) yield highly variable results that depend on patient cooperation and day‐to‐day performance, whereas stapedius reflex thresholds improved in seven of eight ears after 2 years of ERT.