Faculty Bibliography

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds

We recently published data suggesting the presence of an intrinsic sinus node abnormality in a subgroup of patients with the postural tachycardia syndrome (POTS). Based on the hypothesis that more widespread abnormalities of cardiac electrophysiologic properties may be present in POTS, we undertook a study to compare cardiac conduction and repolarization at different heart rate levels in patients with POTS and healthy controls. Eleven healthy controls and fourteen patients with POTS participated in the study. Acquisition of 12-lead electrocardiogram recordings were made during supine rest and during gradual head-up tilt. The heart rate of controls was titrated by isoproterenol infusion to match the heart rate of patients. Indices for cardiac conduction (PR interval, QRS duration, and R wave axis) and repolarization (QT interval, QTc interval, and T wave axis) were then compared at different heart rate levels. The PR interval decreased with increasing heart rate in controls more than in patients, resulting in a significantly longer PR interval in patients at the fastest heart rate level. The QT and QTc intervals were significantly shorter in POTS over the entire analyzed heart rate range. The T wave axis decreased with increasing heart rate in patients only. This resulted in a significantly lower T wave axis in patients at the fastest heart rate level. Our data suggest abnormalities of atrioventricular conduction and ventricular repolarization in patients with POTS. These findings may reflect intrinsic cardiac electrophysiologic abnormalities or may be secondary due to abnormalities of cardiac autonomic innervation

Although cardiorespiratory complications contribute to the high morbidity/mortality of familial dysautonomia (FD), the mechanisms remain unclear. We evaluated respiratory, cardiovascular, and cerebrovascular control by monitoring ventilation, end-tidal carbon dioxide (CO2-et), oxygen saturation, RR interval, blood pressure (BP), and midcerebral artery flow velocity (MCFV) during progressive isocapnic hypoxia, progressive hyperoxic hypercapnia, and during recovery from moderate hyperventilation (to simulate changes leading to respiratory arrest) in 22 subjects with FD and 23 matched control subjects. Subjects with FD had normal ventilation, higher CO2-et, lower oxygen saturation, lower RR interval, and higher BP. MCFV was also higher but depended on the higher baseline CO2-et. In the FD group, whereas hyperoxic hypercapnia induced normal cardiovascular and ventilatory responses, progressive hypoxia resulted in blunted increases in ventilation, paradoxical decreases in RR interval and BP, and lack of MCFV increase. Hyperventilation induced a longer hypocapnia-induced apneic period (51.5 +/- 9.9 versus 11.2 +/- 5.5 seconds, p < 0.008) with profound desaturation (to 75.8 +/- 3.5%), marked BP decrease, and RR interval increase. Subjects with FD develop central depression in response to even moderate hypoxia with lack of expected change in cerebral circulation, leading to hypotension, bradycardia, hypoventilation, and potentially respiratory arrest. Higher resting BP delays occurrence of syncope during hypoxia. Therapeutic measures preventing hypoxia/hypocapnia may correct cardiovascular accidents in patients with FD

BACKGROUND: Healthy ageing has several effects on the autonomic control of the circulation. Several studies have shown that baroreflex-mediated vagal control of the heart deteriorates with age, but so far there is little information regarding the effect of ageing on sympathetically mediated baroreflex responses. The aim of this study was to assess the effects of ageing on baroreflex control of the heart and blood vessels. MATERIALS AND METHODS: In 40 healthy volunteers, aged 20-87 years, we applied oscillatory neck suction at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was maintained at 0.25 Hz. Blood pressure, electrocardiographic RR intervals and respiration were recorded continuously. Spectral analysis was used to evaluate the magnitude of the low-frequency (0.03-0.14 Hz) and high-frequency (0.15-0.50 Hz) oscillations in the RR interval and blood pressure. Responses to neck suction were assessed as the change in power of the RR interval and blood pressure fluctuations at the stimulation frequency from baseline values. RESULTS: Resting low- and high-frequency powers of the RR interval decreased significantly with age (P < 0.01). However, the low-frequency power of systolic blood pressure did not correlate with age. Spontaneous baroreflex sensitivity (alpha-index) showed a significant inverse correlation with age (r = -0.46, P < 0.05). Responses of the RR interval and systolic blood pressure to 0.1 Hz neck suction stimulation were not related to age, however, the RR interval response to 0.2 Hz neck suction declined significantly with age (r = -0.61, P < 0.01). CONCLUSIONS: These results confirm an age-related decrease in cardiovagal baroreflex responses. However, sympathetically mediated baroreflex control of the blood vessels is preserved with age

AIM: The purpose of this study was to investigate, in a community-based population, the frequency of stroke-related urinary incontinence (

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29+/-4 years) we applied sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to -50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (-10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at -10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing

BACKGROUND: Relatively little is known about physiological cerebrovascular haemodynamics during physical stress in elderly healthy individuals. The aim of this study was to determine the effect of ergometer stress on cerebrovascular haemodynamics in elderly healthy individuals in comparison with young healthy individuals, using non-invasive methods. METHODS: Continuous middle cerebral artery blood flow velocity (CBFV; transcranial Doppler ultrasound), beat-to-beat blood pressure, heart rate and transcutaneous pCO(2) were measured in response to 3 min ergometer exercise stress in 18 elderly healthy subjects (mean age +/- SD 66.5 +/- 5.8 years) and 18 healthy young subjects (mean age +/- SD 29.4 +/- 4.7 years). Pulsatility index (PI) was used as a parameter for cerebrovascular resistance. The subjects were in a supine position with an elevated trunk and performed exercise by pedalling on an ergometer, generating 75-100 W. Statistical analysis was carried out using MANOVA, a general linear model with repeated measures. RESULTS: In both groups, blood pressure increased significantly (p < 0.001) with time during exercise, with no significant differences between the groups or regarding interaction (time sequence/group factor). Heart rate increased significantly with time during exercise (p < 0.001) and was significantly more prominent (p = 0.002) and prolonged (p < 0.001) in the young group. pCO(2) did not differ with time or between the groups and with regard to interaction. Mean CBFV (MFV) increased significantly during time (p < 0.001). Between the groups, there was no significant difference (p = 0.836), but with regard to interaction (time sequence/group factor), there was a significant delay in MFV increase in the group of young subjects (p = 0.002). The PI, a measure of cerebrovascular resistance, increased significantly with time without significant differences between the groups (p = 0.061), but was significantly delayed in the elderly regarding the interaction time sequence/group factor (p < 0.001). CONCLUSION: The cerebrovascular changes during ergometer exercise may reflect the combined activation of the cerebrovascular autoregulative mechanisms (predominantly neurogenic and myogenic). In healthy normotensive elderly subjects, cerebral autoregulatory capacity is retained but delayed in response to ergometer stress compared with young healthy subjects. We speculate that these findings may contribute to a higher risk of cerebral hypoperfusion in the elderly

After 1 week of flu-like illness, a 64-year-old man developed rapidly progressive mononeuritis multiplex involving the right arm and both legs. Serologic studies identified Coxiella burnetii as the cause of the febrile disease (Q fever). Fourteen days doxycycline treatment (200 mg daily) induced rapid and complete recovery. After 6 months, flu-like symptoms, weakness and hypalgesia of the right leg reappeared. Antibody titers again identified Q fever. Doxycycline was re-established and induced prompt recovery. Q fever has been associated with various neurologic complications such as meningoencephalitis, cerebellitis, optic neuritis or polyneuroradiculitis. This is the first report on Q fever related mononeuritis multiplex. Prolonged antibiotic treatment may be required to prevent relapsing infection from the resistant bacterium

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

OBJECTIVE: Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease which has no known cure and limited symptomatic treatment. While coping strategies in more common diseases are widely assessed, coping is poorly understood in ALS. METHODS: We examined 41 ALS patients using a standardised interview, a validated coping self-rating questionnaire and a self-rating depression scale. The evaluation was repeated after six months. RESULTS: 'Loss of speech', 'loss of mobility' and 'the poor prognosis' were the most frequent answers in the standardised interview to questions regarding the worst aspect of the disease. Pain was seldom mentioned. 'Family members' were most helpful in coping with the disease, followed by 'unspecific mechanisms' and 'technical aids'. None of our patients expressed a wish for assisted suicide. In comparison with other fatal diseases, patients with ALS had similar rankings in the coping mechanism of 'rumination', but lower rankings in 'search for social integration', 'defence of fear', 'search for information and communication'. In contrast,* 'search for hold in the religion' was of high importance for our ALS patients. In the follow-up examination the importance of 'search for information and communication' increased. CONCLUSION: The results emphasise the importance of 'loss of speech' and the importance of the caring family as well as the availability of technical aids in ALS. Coping in ALS seems to be based mainly on 'rumination' and *'hold in the religion', but the increasing importance of 'search for information' indicates that the sustained offer of information is essential