Measurement of skin vasoconstrictor response in healthy subjects

OBJECTIVES: Laser Doppler flowmetry enables non-invasive quantification of skin blood flow and its sympathetically mediated change. Four different maneuvers were performed in 60 healthy subjects aged 20-78 years to investigate their variability, reproducibility and to determine the influence of gender, age and height. MATERIAL AND METHODS: Skin blood flow was measured on the pulp of both index fingers using laser Doppler flowmetry. Vasoconstriction was induced by deep inspiratory gasp, arm dependency, acoustic stimulation and a modified cold pressor test. RESULTS: More than 95% of normal subjects showed a vasoconstrictor response to cold pressure test and 100% to inspiratory gasp. In all other maneuvers vasoconstrictor response was less reliable. The magnitude of vasoconstrictor responses decreased with age in all maneuvers, while latencies remained unchanged. Only during inspiratory gasp men showed more pronounced vasoconstrictor response compared with women. Body height influenced latencies if peripheral stimuli were applied like in the cold pressor and arm dependency tests. CONCLUSIONS: Inspiratory gasp and the modified cold pressor test were found to be more suitable maneuvers for routine clinical testing than arm dependency and acoustic stimulation. Normal data also for side differences are provided as a base for routine clinical testing in systemic and unilateral neurological disorders.     

Skin vasomotor reflex responses in two contrasting groups of autonomic failure

Background & Aim A variety of stimuli such as deep inspiration, isometric exercise and mental arithmetic, result in a transient vasoconstriction,mediated by sympathetic efferent nerves, in the skin of the fingers and toes of healthy controls (Skin Vasomotor Reflex: SkVR). Multiple system atrophy (MSA) and pure autonomic failure (PAF) provide contrasting models of autonomic failure. In MSA the lesion is central and preganglionic, whilst in PAF the lesion site is peripheral and postganglionic. We evaluated the SkVR in response to various stimuli in MSA and PAF, to determine differences in skin vasomotor involvement between these two patient groups. Methods 25 subjects (10 MSA, 7 PAF, 8 healthy controls) were studied. Baseline recordings of skin blood flow were obtained with a laser Doppler probe on the left index finger pulp and forearm. The subject then underwent a variety of stimuli with rest periods in between to reestablish baseline SkBF. These stimuli were: single deep inspiration (inspiratory gasp); mental arithmetic; bilateral leg elevation and cutaneous cold. Results Healthy control subjects demonstrated marked SkVRs on the finger pulp to each of the stimuli of a magnitude similar to those seen in previous studies, but no SkVRs on the forearm. In MSA SkVRs to inspiratory gasp on the finger pulp were reduced relative to controls. In PAF SkVRs were reduced relative to controls or MSA. The magnitude of SkVR response to gasp and cutaneous cold in PAF was significantly less than in healthy controls. In addition, the magnitude of the response in PAF was significantly less than in MSA for inspiratory gasp. Conclusions PAF showed a decreased SkVR response to all 4 stimuli, the response being significantly less than controls (for inspiratory gasp and cutaneous cold) or MSA (cutaneous cold inspiratory gasp). The decreased responses in PAF may reflect the extensive postganglionic sympathetic denervation seen in this group. The measurement of SkVR may therefore provide a non-invasive aid to the differentiation of MSA and PAF.     

Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

Fabry disease is a rare X-linked lysosomal storage disorder. The mutations result in a deficiency of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycosphingolipids in the vascular endothelial cells and many other tissues. Given the X-linked inheritance, male patients are severely affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically. The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p = 0.006) in female Fabry patients. This indicates that female Fabry patients have a significant loss of small-fibre function and demonstrates that it is possible to evaluate this by a non-invasive method.     

Fabry disease: impaired autonomic function

Previous reports of extensive lipid accumulation within neurons of the autonomic nervous system in Fabry disease suggest an anatomicopathologic basis for the peculiar pain, diminished sweating, and gastrointestinal symptoms experienced in this disorder. To further assess autonomic function in Fabry disease, noninvasive clinical tests were performed on 10 patients. Diminished sweating was found in each; the loss was approximately uniform proximally and distally, suggesting sweat gland dysfunction rather than autonomic neuropathy. Impaired pupillary constriction with pilocarpine, and reduced saliva and tear formation were found in half the patients. Disordered intestinal mobility was demonstrated in the oldest patients. In all cases, the cutaneous flare response to scratch and intradermal histamine was diminished, and pruritus was not experienced. Signs of autonomic dysfunction are present in Fabry disease and correlate with the known lipid deposition in autonomic neurons.     

Skin biopsy for assessment of autonomic denervation in Parkinson’s disease

Summary. Autonomic dysfunction in Parkinson’s disease (PD) is considered a late complication of the disease or an adverse effect of anti-parkinsonian medications. Morphological changes are demonstrated only by postmortem examination. The study objective was to evaluate peripheral autonomic neural involvement in PD using punch skin biopsy. The study sample included 22 patients (mean age 50 ± 7.7 years, mean disease duration 5.3 ± 3.8 years) and 19 controls. Four-millimeter skin biopsies were immunohistochemically stained with anti-PGP 9.5 antibody. Autonomic innervation of the blood vessels, sweat glands, and erector pili muscles was assessed and rated from 0 (normal) to 2 (severe). Cutaneous autonomic innervation was decreased in patients compared to controls. Semi quantitative analysis demonstrated reduced autonomic innervation of the blood vessels (1.0 ± 0.8 vs. 0.42 ± 0.8 in controls; p < 0.02), of sweat glands (0.95 ± 0.67 vs. 0.47 ± 0.61; p < 0.02) and of the erector pili muscles (1.06 ± 0.55 vs 0.21 ± 0.42; p < 0.001). This method demonstrates that the peripheral autonomic system is affected in PD at early stage of the disease and that autonomic involvement in PD may be more prevalent than previously thought. R. Dabby and R. Djaldetti contributed equally to this work     

Functional assessment of the sympathetic innervation of the microcirculation of the lower urinary tract: A preliminary report

This paper presents preliminary data on a new method for testing the sympathetic innervation of the urothelium. A flexible laser Doppler probe was introduced into the urethra of two females and two male subjects. The percentage fall in laser Doppler flux following generalized sympathetic stimulation by taking an inspiratory gasp was measured. This resulted in 36%, 32%, 68% and 34% mean drop in urothelial blood flux. In the female subjects, the probe was advanced into the bladder and the procedure repeated, and the gasp resulted in 60% and 83% drop in flux. With laser Doppler fluxmetry, fall in microcirculatory blood flow associated with a generalized increase in sympathetic tone, therefore can be demonstrated. This method may be useful in the assessment of the integrity of the sympathetic innervation of the urothelium in patients with suspected autonomic dysfunction of the genitourinary tract.     

Small fiber dysfunction predominates in Fabry neuropathy.

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.     

Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease

Fabry disease is an X-linked disorder caused by a deficiency of lysosomal alpha-galactosidase A resulting in accumulation of alpha-D-galatosyl conjugated glycosphingolipids. Clinical manifestations include a small-fiber neuropathy associated with debilitating pain and hypohidrosis. We report the effect of a 3-year open-label extension of a previously reported 6-month placebo-controlled enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry disease received 0.2 mg/kg of alpha-galactosidase A every 2 weeks. The effect of ERT on neuropathic pain scores while off pain medications, quantitative sensory testing, quantitative sudomotor axon reflex test (QSART), and thermoregulatory sweat test (TST) is reported. In the patients who crossed-over from placebo to ERT (n = 10), mean pain-at-its-worst scores on a 0-10 scale decreased (from 6.9 to 4.5). There was a significant reduction in the threshold for cold and warm sensation in the foot. At the 3-year time-point, pre-ERT sweat excretion in 17 Fabry patients was 0.24 +/- 0.33 microl/mm(2) vs. 1.05 +/- 0.81 in concurrent controls (n = 38). Sweat function improved 24-72 h post-enzyme infusion (0.57 +/- 0.71 microl/mm(2)) and normalized in four anhidrotic patients. TST confirmed the QSART results. We conclude that prolonged ERT in Fabry disease leads to a modest but significant improvement in the clinical manifestations of the small-fiber neuropathy associated with this disorder. QSART may be useful to further optimize the dose and frequency of ERT.     

Tilt-table test during transcranial Doppler monitoring in Parkinson's disease

Cardiovascular autonomic dysfunction can occur in Parkinson's disease (PD) and intracranial vascular modifications following orthostatism may be relevant to diagnostic and therapeutic decision-making. We performed transcranial Doppler monitoring of right middle cerebral artery (MCA) at rest and during passive 70 degrees tilt in 19 patients with idiopathic PD and in 19 age-matched normal controls. Brachial arterial blood pressure (systolic, diastolic and mean), cardiac frequency (CF), respiratory frequency and mean velocity (MV) of the MCA were recorded after 10 min of rest in supine position, and each minute during 9 min of tilting and 5 min of restored clinostatic position. The pulsatility and cerebrovascular resistances (CVR) indexes were calculated. At rest there was no significant difference in blood pressure, CF, respiratory frequency and MCA mean velocity between patients and controls. During tilt test, PD patients showed a trend to higher pulsatility index values (p=0.09) and significant lower diastolic blood pressure (p=0.001), while there was no significant difference in CVR index. In conclusion, PD patients showed mild hypotensive response to orthostatic stress, with intracranial compensatory vasodilation. Our findings suggest a preserved intracerebral autoregulation in PD without symptoms of orthostatic intolerance.     

Postischemic cutaneous hyperperfusion in the presence of forearm hypoperfusion suggests sympathetic vasomotor dysfunction in Fabry disease

In Fabry disease, deficiency of -galactosidase A induces glycolipid storage that accounts for neuropathy, renal failure, myocardial infarction and stroke. Vascular crises may be precipitated by stressful conditions. To evaluate pathomechanisms of overall organ versus microvessel perfusion in response to ischemic challenge, we assessed resting and postischemic forearm and skin blood flow in Fabry patients. In 14 Fabry patients and 15 healthy controls, we measured resting and postischemic forearm blood flow by means of venous occlusion plethysmography and superficial index finger skin blood flow using laser Doppler flowmetry. At rest, arterial inflow into the limb was averaged from eight venous occlusion measurements and expressed as % volume change/minute. Postischemic plethysmographic inflow was determined from the peak influx during the first venous occlusion following three minutes of ischemia. Transcutaneous oxygen and carbon dioxide partial pressures at the forearm were monitored continuously. At rest, plethysmographic forearm perfusion was 15% lower in patients than in controls (p < 0.05) while skin blood flow did not differ between patients and controls. After ischemia, forearm hyperperfusion was less pronounced in patients than in controls (p < 0.05), while skin perfusion almost doubled in patients but increased only slightly in controls. Transcutaneous oxygen and carbon dioxide pressures did not differ between both groups. We conclude that the reduced overall limb perfusion at rest and after ischemia is likely to be due to lipid deposition with increased rigidity, decreased distensibility and lowered diameter of the vasculature. The exaggerated skin perfusion after ischemia might be attributable to the small fiber neuropathy of Fabry patients with deficient vasoconstrictor tone and enhanced vasodilatation due to hypersensitivity of denervated intracutaneous nerve fibers towards ischemia.     

The sympathetic skin response in peripheral autonomic failure — evaluation in pure autonomic failure, pure cholinergic dysautonomia and dopamine-beta-hydroxylase deficiency

The sympathetic skin response (SSR) detects changes in the electrical potential in the skin in response to physiological and electrical stimuli and, therefore, may indicate the integrity of sympathetic cholinergic neural pathways to sweat glands. This has been evaluated in 21 patients with three different forms of peripheral autonomic failure. Of these, 15 had pure autonomic failure (PAF) without additional neurological features; investigations indicated both sympathetic and parasympathetic failure. Four patients had pure cholinergic dysautonomia (PCD), with clinical and laboratory features indicating only cholinergic failure. Two siblings had dopamine-betahydroxylase (DBH) deficiency with only sympathetic adrenergic failure. None was on drugs affecting cholinergic function. Ten normal individuals were aged-matched with PAF patients and studied as controls. The SSR was recorded from the palmar hand and plantar foot surfaces, using previously described techniques, in response to physiological (auditory, cough and inspiratory gasp) and electrical stimuli. Nerve conduction studies excluded an associated motor or sensory neuropathy.The SSR was present in all normal individuals, and in both patients with DBH deficiency who had preserved cholinergic and subdomotor function. It was absent in all 15 PAF and all four PCD patients with impaired cholimergic function. Therefore, we conclude that the SSR reflected sympathetic cholinergic function in these three different groups with peripheral autonomic failure. Clin Auton Res 8:133–138     

Adult polyglucosan body disease in a patient originally diagnosed with Fabry’s disease

Adult polyglucosan body disease is a rare autosomal recessive disease, caused by glycogen branching enzyme gene mutations, characterised by urinary dysfunction, spastic paraplegia with vibration sense loss, peripheral neuropathy, and cognitive impairment. Fabry’s disease is an X-linked lysosomal storage disorder caused by α-galactosidase A gene mutations; neurological manifestations include cerebrovascular accidents, small-fibre neuropathy and autonomic dysfunction. Here, we report the case of a 44-year-old Sicilian male with stroke-like episodes, hypohidrosis and mild proteinuria, which led to the diagnosis of Fabry’s disease after a hemizygous mutation (p.Ala143Thr) in α-galactosidase A gene was detected. Subsequently, he developed progressive walking difficulties and dementia, which were considered atypical for Fabry’s disease. Therefore, we performed additional investigations that eventually led to the diagnosis of adult polyglucosan body disease caused by two novel missense mutations (p.Asp413His and p.Gly534Val) in the glycogen branching enzyme gene. Recently, the pathogenic role of the p.Ala143Thr mutation in causing Fabry’s disease has been questioned. This case underlines the importance of performing further investigations when facing with atypical features even in the presence of a genetic diagnosis of a rare disease.     

Alterations in cardiovascular autonomic function tests in idiopathic hyperhidrosis

We performed cardiovascular autonomic function tests to assess sympathetic and parasympathetic functions in patients with idiopathic hyperhidrosis. We studied 35 patients with idiopathic hyperhidrosis and 35 age- and sex-matched controls. A thermoregulatory sweat test (TST) was performed in all subjects. Sweating was qualitatively (Minor's test at 22°C) and quantitatively (skin conductance) evaluated. Orthostatism, tilt to 65°, cold pressor test, deep breathing, Valsalva maneuver and hyperventilation were performed in patients and controls. A greater fall in blood pressure values was observed in patients than in controls in the upright tests (p<0.05). In particular, postural hypotension was present in a subgroup of patients (34%), in whom changes in lying-to-standing blood pressure and heart rate were greater (p<0.001) than those of the remaining patients. The TST revealed that the total body sweat rate (ml/cm(2)/min) was more pronounced in patients with postural hypotension (p<0.001) than in the other patients and controls. The skin conductance values of patients with postural hypotension were higher (p<0.001) than those of the remaining patients. A positive correlation was found between skin conductance values and postural hypotension. Dehydration and poor water intake may play a role in postural hypotension in patients with severe hyperhidrosis and pronounced thermoregulatory sweating. A significantly marked increase in parasympathetic function was observed in patients. Responses to deep breathing, Valsalva maneuver and hyperventilation were significantly greater in patients (p<0.001) than in controls. Idiopathic hyperhidrosis seems to be a complex dysfunction that involves autonomic pathways other than those related to sweating.     

Effect of generalized sympathetic activation by cold pressor test on cerebral hemodynamics in diabetics with autonomic dysfunction

BACKGROUND: We examined the effects of the cold pressor test on the cerebral circulation in diabetics with autonomic dysfunction without orthostatic hypotension using transcranial Doppler. METHODS: Twenty diabetics with autonomic dysfunction and 19 age-matched healthy controls participated in the study. The mean arterial blood velocity was measured in the middle cerebral artery during the cold pressor test together with the mean arterial blood pressure. RESULTS: The mean arterial blood velocity significantly (p < 0.01) increased during the 1st, 2nd, and 3rd min of the cold pressor test by 10.6, 14.1, and 13.4%, respectively, in the control subjects and by 5.8, 7.2, and 6.8%, respectively, in the diabetics. Simultaneously, the mean arterial blood pressure significantly (p < 0.01) increased by 12, 26, and 23%, respectively, in the controls and by 9.4, 12.4 and 12.9%, respectively, in the diabetics. The increases in the mean arterial velocity as well as in the mean arterial blood pressure were significantly higher in the controls than in the diabetics (p < 0.01). The change in the mean arterial blood pressure related significantly to the change in the mean arterial blood velocity both in the controls (p < 0.01, r = 0.76) and in the diabetics (p < 0.01; r = 0.59). The slope of the regression line was significantly steeper in the controls (b = 0.42, SE = 0.05) as compared with the diabetics with autonomic dysfunction (b = 0.27, SE = 0.05; p = 0.02). Moreover, also the relative increase in the cerebrovascular resistance index was higher in the controls than in the diabetics (p < 0.05). CONCLUSION: These findings in the diabetics with autonomic neuropathy, but without orthostatic hypotension, suggest a failure in the cerebral autoregulation due to impaired cerebrovascular neurogenic control.     

Sympathetic vasoconstrictor reflexes in Parkinson's disease with autonomic dysfunction

Centrally and locally elicited sympathetic vasoconstrictor responses were examined in 12 patients with symptoms and signs of cardiovascular autonomic dysfunction due to Parkinson's disease. The sympathetic reflex mechanisms were measured in skeletal muscle and subcutaneous tissue of the arm and leg using the 133-Xenon washout technique. This method allows differentiation between local and central sympathetic reflexes in different tissues. The results indicate an abolished centrally mediated vasoconstrictor response in skeletal muscle in the arm and a decreased response in skeletal muscle in the leg and in subcutaneous tissue. This is in agreement with an autonomic dysfunction located in the central nervous system. A possible spinal sympathetic reflex controlling blood flow in subcutaneous tissue and leg muscles is considered. The sympathetic vasoconstrictor responses in parkinsonian patients without autonomic failure were of normal magnitude and the responses were not affected by long-term levodopa treatment.     

Autonomic function and human immunodeficiency virus infection

We compared autonomic function in 26 patients infected by the human immunodeficiency virus (HIV) (18 AIDS and 8 ARC) to 22 controls. A significant decline in autonomic function was present across groups. Autonomic dysfunction correlated strongly with signs of HIV-associated nervous system disease. We observed significant differences across groups in tests of heart rate variation (expiratory-inspiratory ratio, maximum minus minimum heart rate difference, and mean square successive difference), the mean arterial blood pressure fall to tilting, and the blood pressure response to isometric exercise. A trend of declining autonomic function from controls to AIDS was present in the 30:15 ratio, the Valsalva ration, the systolic blood pressure fall to standing and tilt, and the cold pressor test. We did not observe any correlation between autonomic dysfunction and individual neurologic signs, prior therapeutic agents, and concurrent HIV-associated inflammatory or neoplastic processes. This study provides support for the presence of autonomic dysfunction in association with HIV infection. Autonomic dysfunction occurs more frequently and with greater severity in patients with AIDS; however, it may be present in the early stages of HIV infection and appears to progress during the illness.     

Sympathetic dysfunction of central origin in patients with ALS

Amyotrophic lateral sclerosis (ALS) is a severe, progressive disease affecting both the central and peripheral parts of the motor nervous system. Some studies have shown unequivocal indications of a more disseminated disease also affecting the autonomic nervous system. We therefore evaluated the centrally and peripherally mediated autonomic vascular reflexes by (i) the local 133-Xenon washout technique, and (ii) the head-up tilt table test. The results correlated to clinical scores. We examined nine ALS patients and 15 age-matched controls. The 133-Xenon washout test showed a significant reduction in the centrally mediated sympathetic vasoconstrictor response, but a preserved locally mediated response in the patients. In the head-up tilt table test, the patients had a significantly higher mean arterial blood pressure (MAP) compared with controls, probably due to a general increase in vascular resistance. There were no correlations between the ALS Severity Scores and blood flow changes, diastolic blood pressure or MAP. Our study supports previous results, but indicates abnormalities consistent with a solely centrally located sympathetic dysfunction in ALS, independent of the stage of the disease.     

Cutaneous sympathetic function in patients with multiple system atrophy

Some procedures increase the sweat output (SSwR; sympathetic sweat response) and reduce the cutaneous blood flow (SVR; skin vasomotor reflex) in the hand. We evaluated SSwRs and SVRs to deep inspiration, mental arithmetic, exercise, and tactile stimulation in 40 MSA patients and 15 healthy controls. We also conducted head-up tilt tests and R-R interval variation tests (CV_R-R). SSwRs were present in all controls, but absent in 19 (47.5 %) of the MSA patients. The mean SSwR amplitudes in the MSA group were significantly lower than those in the control group. SVRs were evoked in all subjects except 3 MSA patients. There were no marked differences in SVR amplitudes between the two groups. Orthostatic hypotension and low CV_R-R values were seen in 18 (45 %) and 13 (32.5 %) of the MSA patients, respectively. SSwR amplitudes correlated significantly with postural fall in blood pressure and CV_R-R values in the MSA group. SSwRs were absent in about half of the MSA patients, and the SSwR results correlated with those of the cardiovascular autonomic tests. The SVRs were not severely disturbed in the MSA patients. We considered SSwR a useful index for the detection of autonomic dysfunction in MSA. Received: 7 January 2002, Accepted: 4 June 2002 Correspondence to: Masato Asahina, M. D.     

Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease

Abstract. 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.     

Autonomic nerve function in adults with cyclic vomiting syndrome: a prospective study

Background Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that is characterized by recurrent episodes of intense vomiting. There are several postulated mechanisms involved in its pathogenesis and one potential explanation for this disorder may be linked to autonomic dysfunction. The aim of our study was to evaluate autonomic nerve function in patients with CVS prospectively. Methods We tested the sympathetic nervous system through postural changes in heart rate (HR) and blood pressure and the thermoregulatory sweat test. The parasympathetic nervous system was tested through the HR response to deep breathing (R‐R variability on EKG). Key Results A total of 20 patients who met Rome III criteria for CVS, 14 (70%) women and 6 (30%) men, and 20 controls were enrolled in the study. A total of 17 (85%) CVS subjects and 2 (10%) controls had abnormalities on thermoregulatory sweat testing (P < 0.001). A total of 7 (35%) patients and one control subject had evidence of postural tachycardia (P = 0.04) with an increase in HR > 30 on standing. Of the subjects, 18 (90%) had either abnormal sudomotor function or postural tachycardia or both. The HR response to deep breathing was normal in 19 (95%) subjects with CVS and 18 (95%) controls. Conclusions & Inferences The results of this study suggest that the majority of subjects (90%) with CVS have impairment of the sympathetic nervous system with postural tachycardia and/or sudomotor dysfunction while parasympathetic nerve function appears to be intact. These findings of dysautonomia in CVS have implications in both the diagnosis and treatment of these patients.