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In familial dysautonomia (1713), i.e. Riley-Day-syndrome, sympathetic cardiovascular function, as well as afferent temperature and pain mediating neurons, are significantly reduced. Thus, it was questioned if cold pressor test (CPT), which normally enhances sympathetic outflow and induces peripheral vasoconstriction by the activation of thermo- and nociceptive system activation, could be used to assess sympathetic function in FD. To evaluate whether CPT can be used to assess sympathetic activation in FD, we performed CPT in 15 FD patients and IS controls. After a 35-min resting period, participants immersed their right hand and arm up to the elbow into 0-1°C cold water while we monitored heart rate (HR), respiration, beat-to-beat radial artery blood pressure (BP), and laser Doppler skin blood flow (SBF) at the right index finger pulp. From these measurements, heart rate variability parameters were calculated: root mean square of successive differences (RMSSD), coefficient of variation (CV), low and high frequency (LF, HF) power spectra of the electrocardiogram (ECG). All participants perceived cold stimulation and indicated discomfort. In controls, SBF decreased and HR and BP increased rapidly upon CPT. After 60 s, SBF indicated secondary vasodilatation in six controls, BP rise attenuated and HR returned to baseline in all controls. In the patients, SBF remained unchanged, HR and BP increased significantly, but after 50-60 s of CPT and changes were lower than in controls (p*LT0.05). RMSSD and CV decreased and LF increased significantly only in the controls. We conclude that CPT activates sympathetic HR and BP modulation despite impaired pain and temperature perception in FD patients. BP increase in the presence of almost unchanged SBF might be due to HR increase and to nociceptive arousal and emotionally induced catecholamine release as seen in emotional crises of FD patients. CPT assesses sympathetic cardiovascular responses independently from baroreflex... [ABSTRACT FROM AUTHOR]

Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed., Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance., Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs., Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications., (© 2016 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: 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)., Objective: To determine whether OH recovers faster with combined supine repositioning and abdominal compression than with supine repositioning alone., Methods: In 9 patients with FD (17.8 ± 3.9 years) and 10 healthy controls (18.8 ± 5 years), we assessed 2-min averages of BPsys, BPdia, and heart rate (HR) during supine rest, standing, supine repositioning, another supine rest, second standing, and supine repositioning with abdominal compression by leg elevation and flexion. We determined BPsys- and BPdia-recovery-times as intervals from return to supine until BP reached values equivalent to each participant's 2-min average at supine rest minus two standard deviations. Differences in signal values and BP-recovery-times between groups and positions were assessed by ANOVA and post hoc testing (significance: P < 0.05)., Results: Patients with FD had pronounced OH that improved with supine repositioning. However, BP only reached supine rest values with additional abdominal compression. In controls, BP was stable during positional changes. Without abdominal compression, BP-recovery-times were longer in patients with FD than those in controls, but similar to control values with compression (BPsys: 83.7 ± 64.1 vs 36.6 ± 49.5 s; P = 0.013; BPdia: 84.6 ± 65.2 vs 35.3 ± 48.9 s; P = 0.009)., Conclusion: Combining supine repositioning with abdominal compression significantly accelerates recovery from OH and thus lowers the risk of hypotension-induced cerebral hypoperfusion., (© 2012 John Wiley & Sons A/S.)

Objective: Tachyarrhythmias are common during epileptic seizures while bradyarrhythmias or asystoles are less frequent. Ictal asystole might be related to epilepsy-induced cardiac sympathetic denervation., Methods: To evaluate cardiac post-ganglionic denervation in epilepsy patients with ictal asystoles we assessed I123-meta-iodobenzylguanidine (MIBG) as a marker of post-ganglionic cardiac norepinephrine-uptake, using single photon emission computed tomography (MIBG-SPECT)., Results: In five of 844 patients with presurgical video-electroencephalography-monitoring, we recorded ictal asystoles during nine of 37 seizures. Asystole patients underwent cardiologic examination (Holter-electrocardiogram, echocardiogram) and cardiac MIBG-SPECT. We compared cardiac MIBG uptake in the asystole patients to the uptake in 18 temporal lobe epilepsy (TLE) patients without bradyarrhythmias and in 14 controls without cardiac or neurological disease. As the cardiological examinations were unremarkable in all subjects, the heart/mediastinum-MIBG-uptake ratios (H/M-ratios) differed significantly between the three groups (P = 0.004). H/M-ratios were lower in asystole TLE patients (mean +/- SD: 1.58 +/- 0.3) than in patients without asystole (1.81 +/- 0.18; P = 0.037) or controls (1.96 +/- 0.16)., Conclusions: Pronounced reduction in cardiac MIBG uptake of asystole patients indicates post-ganglionic cardiac catecholamine disturbance. Impaired sympathetic cardiac innervation limits adjustment and heart rate modulation, and may increase the risk of asystole and ultimately sudden unexpected death in epilepsy (SUDEP).

Background: Sildenafil, frequently used as on demand medication for the treatment of erectile dysfunction (ED), has been suggested to improve endothelial function but also to alter blood pressure (BP) and induce sympathetic activation. In people with type 2 diabetes mellitus (T2DM), a high-risk population, the safety profile and the effects on endothelial function of a maximal sildenafil dose (100 mg) have not been investigated and therefore constituted the aim of our study., Methods: A double-blind, placebo-controlled, cross-over trial using a single dose of 100 mg sildenafil or placebo has been conducted in 40 subjects with T2DM without known CVD. Haemodynamic parameters, flow mediated dilatation (FMD) in brachial artery, cardiovascular autonomic function tests and spontaneous baroreflex sensitivity (BRS) were measured., Results: Sixty minutes after administration of sildenafil but not placebo, a fall of supine systolic blood pressure (SBP) (-5.41 +/- 1.87 vs. + 0.54 +/- 1.71 mmHg) and diastolic blood pressure (DBP) (-4.46 +/- 1.13 vs. + 0.89 +/- 0.94 mmHg), as well as orthostatic SBP (-7.41 +/- 2.35 vs. + 0.94 +/- 2.06 mmHg) and DBP (-5.65 +/- 1.45 vs. + 1.76 +/- 1.00 mmHg) during standing occurred, accompanied by an increase in heart rate (+1.98 +/- 0.69 vs. - 2.42 +/- 0.59 beats/min) (all p < 0.01 vs. placebo). Changes in BP to standing up, FMD, time domain and frequency domain indices of heart rate variability (HRV) and BRS were comparable between sildenafil and placebo., Conclusions: Sildenafil administered at a maximum single dose to T2DM men results in a mild increase in heart rate and decrease in BP, but it induces neither an acute improvement of FMD nor any adverse effects on orthostatic BP regulation, HRV and BRS., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Objective: To evaluate the impact of vagus nerve stimulation (VNS) on heart rate and blood pressure (BP) modulation in epilepsy patients., Material and Methods: Twenty-one epilepsy patients with VNS were tested during on (60 s) and off (5 min) phases. We monitored BP, RR intervals (RRI) and respiration. Spectral analysis was performed in low- (LF: 0.04-0.15 Hz) and high-frequency bands (HF: 0.15-0.5 Hz). For coherences above 0.5, we calculated the LF transfer function between systolic BP and RRI, and the HF transfer function gain and phase between RRI and respiration. Differences between the on and off phases were evaluated using Wilcoxon test., Results: VNS did not change RRI and BP values. The LF power of BP and the LF and HF power of RRI increased significantly. There was a slight change in the RRI/BP LF gain and the RRI/respiration HF gain (ns). The HF phase between RRI and respiration decreased significantly., Conclusions: Our findings show that VNS influences both sympathetic and parasympathetic cardiovascular modulation. However, our results also show that VNS does not negatively influence autonomic cardiovascular regulation.

Objectives: The aim of this study was to assess baroreflex regulation of the heart rate and blood vessels in migraine patients in comparison with healthy controls., Methods: In 30 migraine patients who were in a headache-free phase, aged 34 +/- 2 years, and 30 healthy controls, aged 34 +/- 3 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 paced at 0.25 Hz. Electrocardiographic RR-intervals, blood pressure and respiration were continuously recorded. Responses to the baroreflex stimulations were assessed as the changes in power of the RR-interval and blood pressure fluctuations at the relevant stimulating frequency from the baseline values., Results: Systolic and diastolic blood pressure responses to the 0.1 Hz neck suction pressure were not significantly different between the patients and controls. The RR-interval oscillatory response to 0.2 Hz neck suction was significantly less (P < 0.05) in the migraine patients (4.45 +/- 0.27 ln ms2) compared with the controls (5.48 +/- 0.36 ln ms2)., Conclusion: These results suggest that baroreflex-mediated cardiovagal responses are reduced in migraine patients. However, the sympathetic-mediated baroreflex control of the blood vessels is intact in the migraine patients. The autonomic nervous system may have a role in the pathophysiology of migraine.

Objectives: Enhanced external counterpulsation (EECP) rhythmically augments blood pressure (BP) by diastolic lower-body compression. Recently, we showed decreased mean cerebral blood flow velocity (CBFVmean) in young healthy persons during EECP, but unchanged CBFVmean in atherosclerotic patients. In this study, we assessed EECP effects on dynamic cerebral autoregulation (CA)., Material & Methods: In 23 healthy persons and 15 atherosclerotic patients we monitored heart rate (HR), mean BP (BPmean) and CBFVmean before and during 5 min EECP. We analyzed spectral powers of HR, BPmean and CBFVmean in the low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency ranges to determine CA from the LF-transfer function gain and phase shift between BPmean and CBFVmean oscillations., Results: EECP increased HR and BPmean, while transfer function gain and phase shift remained stable., Conclusions: Stable gain and phase values suggest that EECP does not compromise CA and, therefore, does not seem to bear cerebrovascular risks., (Blackwell Munksgaard 2004)

Objectives: Intra-aortic counterpulsation is the most frequently used cardiac assist device. However, there are only few studies of the effects of counterpulsation on cerebral blood flow and these report conflicting outcomes. The new enhanced external counterpulsation (EECP) technique reproduces non-invasively the effects of intra-aortic counterpulsation. In this study, we evaluated effects of EECP on blood pressure (BP) and on cerebral flow velocity (CBFV)., Subjects and Methods: Twenty-three healthy controls and 15 atherosclerotic patients each underwent a 5-min session of EECP. Before, during and after EECP we monitored heart rate, beat-to-beat radial artery BP and CBFV., Results: EECP induced a second increase in BP and CBFV during diastole with a significant increase of mean BP and a decrease of systolic BP in patients and controls. Mean CBFV increased in both groups during the first 5 s of EECP. After 3 min of EECP, diastolic CBFV was still higher than at baseline, but systolic CBVF was lower than at baseline; mean CBFV was as low as before EECP in the patients and lower than the baseline values in the controls. Three minutes after ending EECP, mean and systolic BP were lower in the patients than the corresponding baseline values. Otherwise, CBFV and BP values did not differ from baseline in patients and controls., Conclusion: Cerebral autoregulation ensures the constancy of cerebral blood flow even though EECP creates marked systemic changes. In the patients, the decrease of BP after EECP with maintained CBFV indicates an improved BPCBFV relation and a more economic autoregulation.

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., (Copyright Blackwell Munksgaard 2002)

Background and Purpose: Monitoring of the basilar artery (BA) is difficult and has been sparsely performed. The aim of this study was to present physiological data of functional transcranial Doppler sonography (TCD) of the BA during caloric vestibular stimulation in healthy volunteers., Methods: TCD of the BA was performed in 26 healthy volunteers (14 women, 12 men, age 25.1+/-3 years) during caloric vestibular stimulation. Vertigo was documented using electronystagmography (ENG) and a subjective vertigo scale ranging from 0 to 10 points. Simultaneously, capnogpraphy was performed., Results: All subjects experienced vertigo, nausea and oszillopsia during vestibular irrigation. The average subjective vertigo was for a period of 106 s (+/-65.4); the average subjective estimated degree of vertigo was 6.7 points (+/-1.5). In all subjects, ENG demonstrated horizontal nystagm to the left non-irrigated side. In 14 subjects the subjective vertigo was rated by the individuals as extreme (point score > or =7) and in 12 subjects as low (point score <7). Mean flow velocity (MFV) in the BA increased significantly during vestibular irrigation, being more prominent in the initial irrigation and vertigo phase (5.8+/-5.9%, P<0.05) than in the second vertigo phase (2.2+/-8.8%, P<0.05). The calculated pulsatility index (PI), which indicates the condition of the small resistance vessels, decreased significantly (-4.9+/-8.1%; 4.3+/-8.9%, P<0.05) during both phases of vestibular activation. End tidal pCO2 did not change significantly (constant 5.4+/-0.4 Vol%), but respiration frequency was significantly increased during vestibular stimulation (12.3+/-3.8 min(-1) to 16.4+/-5.3 min(-1) and 16.3+/-4.8 min(-1), P<0.05) probably as a vegetative sign of vertigo. The observed MFV- and PI-changes were more prominent, although not quite significant, in the subgroup of subjects who experienced extreme subjective vertigo than in the subgroup who experienced low subjective vertigo., Conclusion: These observations indicate that MFV increase in the posterior circulation is due to activation of the vestibulocerebellum. In addition, it is possible that the previously elaborated MFV increase in the MCA might contribute to MFV increase in the BA via the posterior communicating artery. The difference in the 2 subgroups (extreme vertigo vs. low vertigo) may reflect the great variety of anatomical and physiological conditions of the peripheral vestibular organ, the brainstem anatomy and the corresponding blood supply. For clinical purposes this TCD-test may contribute to the investigation of the vasomotor reserve of the posterior circulation, e.g. in patients with vertebrobasilar ischemia, bilateral vestibular loss or local neurodegenerative disease.

Involvement of the autonomic cardiac nervous system in early stages of amyotrophic lateral sclerosis (ALS) was evaluated in 40 patients. I-123-metaiodobenzylguanidine-single photon emission computed tomography (MIBG-SPECT) and heart rate variability (HRV) yielded information about sympathetic and parasympathetic innervation of the heart. MIBG-SPECT is a sensitive diagnostic method for demonstration of early cardiac sympathetic denervation. Both sympathetic and parasympathetic dysfunction was observed in 16 (40%) out of 40 patients. Mean cardiac MIBG uptake as demonstrated by the heart/mediastinum ratio was significantly reduced in all ALS patients in comparison with controls (P<0.01). The global MIBG-SPECT score was clearly abnormal in 29% and slightly abnormal in 22% of patients. HRV was diminished in 6 of 38 patients, 4 of whom having an abnormal MIBG-SPECT score as well. The presented results indicate that ALS patients with mild to moderate impairment may have evidence of postganglionic sympathetic adrenergic cardiac or cardiovagal denervation. To our knowledge, this is the first study indicating possible postganglionic sympathetic denervation in ALS. The original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease which possibly represents different entities.

The diagnostic sensitivity of Vibrameter and tuning fork examination towards uremic and alcoholic neuropathy was tested in 75 patients. In 40 uremic and 35 alcoholic patients, we compared the sensitivity of neurological examination, nerve conduction studies (NCS) and vibration thresholds assessed at the malleoli by means of Vibrameter and scaled tuning fork. Vibrameter results were correlated with NCS. Polyneuropathy was diagnosed in 52 patients, but in 16 patients diagnosis depended upon inclusion of Vibrameter testing in the examination protocol. In uremic patients, Vibrameter (47.5%) showed abnormalities as often as NCS (45%), and more often than clinical (32.5%) or tuning fork examination (2.5%). In alcoholic patients, Vibrameter revealed abnormalities more often (60%) than NCS (34.3%) or tuning fork (14.3%). Correlations between NCS and vibratory thresholds were low (-0.52 < or = Rs < or = -0.35). Vibrameter studies are far more sensitive than tuning fork tests. The technique complements NCS and refines the diagnosis of uremic and alcoholic neuropathies.

Reports on the incidence of alcoholic polyneuropathies are variable depending on diagnostic tools. In this study, 50 chronic alcoholics with positive MALT (Munich Alcoholism Test) and greater than seven years history of excessive alcohol abuse were examined neurologically. Tibial and peroneal motor and sural nerve conduction velocities (NCV) were studied. Warm and cold perception was evaluated in the area behind the internal malleolus using a Somedic-Thermotest. Thresholds were determined by the method of limits. The effect of a slow, medium and fast temperature change rate on thermal perception was tested. Thirty-eight patients (76%) showed signs of neuropathy. Thermal perception was more often abnormal (62%) than NCV (42%) and clinical examination (56%). A medium temperature change rate of 2.0-2.5 degrees C/s was the most sensitive index of small fiber neuropathy. Thermal threshold measurement proved to be a reliable, sensitive and easy to perform method that should become standard in the examination of polyneuropathies.

Marstock thermotesting evaluates A-delta- and C-fiber functions. To optimize this method, intraindividual variations of vasodilatation, blood flow and sympathetic activity probably biasing thermotest results were imitated by exogenous stimuli which strongly exaggerated these intraindividual variations. In 20 healthy subjects, warm (WT), cold (CT), and heat-pain (HT) thresholds were determined in the morning at the thenar (th), the volar wrist (wr), and behind the malleolus internus (mi). Thresholds at the thenar and the volar wrist were compared with those during severe sweating induced by Minor's test, and to those measured when sympathetic activity had been increased by the ingestion of a high dose of caffeine (0.5 g). Furthermore, the intraindividual variation of local capillary blood flow and vasodilatation was imitated by a rubefacient liniment (Forapin) applied to the three sites. After a local hyperemisation had been induced thermal thresholds were measured and compared to those measured without any stimulation. Local hyperemia did not influence thermal thresholds significantly. Sweating only lowered cold thresholds at the thenar significantly and only slightly raised warm and heat-pain thresholds at the thenar. Caffeine significantly lowered warm thresholds and raised heat-pain thresholds at the thenar. To conclude, the tested exogenous interferences do not disturb thermal perception markedly, especially when testing is not performed at the thenar, but at the volar wrist and when the testing-procedure and parameters are standardised.

Thermal testing was carried out on 55 healthy subjects in order to establish normal results and reproducibility of warm and cold thresholds. Diurnal variations of thresholds were investigated in a further 30 normal subjects. Then the sensitivity of different testing procedures was investigated in 33 patients with diabetes mellitus, but without severe polyneuropathy. Forced choice testing takes 6 times longer than the method of limits, and the results are not considerably different. It is thought that the forced choice algorithm does not provide a method for clinical routine. Another new approach, the double random staircase method, may help to exclude bias without taking too much time.

Thermal tests were performed in 117 healthy subjects on the face, wrist and leg; 32 were tested on the legs with different rates of cooling and warming. Additionally 2 groups of diabetics (37 patients) were tested. Thermotesting was most sensitive on the legs using a rate of temperature change of 2.5-2.8 oC/s. Warm and cold perception should be tested separately. Cold perception testing is most sensitive. Combined tests of warm and cold thresholds as well as the testing of cool pain and heat pain do not improve results. Abnormal cold perception may be an early indicator of diabetic small fibre polyneuropathy, leading to cold trauma and ulcers on the feet.