Oral mucosal blood flow in patients with burning mouth syndrome.

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.

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.

[Erectile dysfunction--value of neurophysiologic diagnostic procedures]. / Erektile Dysfunktion-Wertigkeit neurophysiologischer Diagnoseverfahren.

Neurogenic, particularly autonomic disorders, frequently contribute to the etiology and pathophysiology of erectile dysfunction. Parasympathetic and sympathetic outflow mediates erection. Noncholinergic, nonadrenergic neurotransmitters induce activation of cyclic monophosphates, leading to relaxation of smooth muscles of the corpora cavernosa and by this to tumescence and rigidity, i.e. erection. The diagnosis of neurologic causes of erectile dysfunction requires a detailed history and neurologic examination. Conventional neurophysiological procedures evaluate the function of rapidly conducting, thickly myelinated nerve fibers only. Therefore, techniques such as sphincter ani externus electromyography, latency measurements of the pudendal nerve or bulbocavernosus reflex studies frequently do not contribute to the diagnostic process. The evaluation of small nerve fibers that are essential for erection, for example by means of psychophysical quantitative thermotesting, might improve the diagnosis of neurogenic causes of erectile dysfunction. In addition, the assessment of heart rate variability at rest, during metronomic breathing, Valsalva maneuver, and active standing might be helpful to identify an autonomic neuropathy as the cause of erectile dysfunction.

A simple deep breathing test reveals altered cerebral autoregulation in type 2 diabetic patients.

AIMS/HYPOTHESIS: Patients with diabetes mellitus have an increased risk of stroke and other cerebrovascular complications. The purpose of this study was to evaluate the autoregulation of cerebral blood flow in diabetic patients using a simple method that could easily be applied to the clinical routine screening of diabetic patients. METHODS: We studied ten patients with type 2 diabetes mellitus and 11 healthy volunteer control participants. Continuous and non-invasive measurements of blood pressure and cerebral blood flow velocity were performed during deep breathing at 0.1 Hz (six breaths per minute). Cerebral autoregulation was assessed from the phase shift angle between breathing-induced 0.1 Hz oscillations in mean blood pressure and cerebral blood flow velocity. RESULTS: The controls and patients all showed positive phase shift angles between breathing-induced 0.1 Hz blood pressure and cerebral blood flow velocity oscillations. However, the phase shift angle was significantly reduced (p < 0.05) in the patients (48 +/- 9 degrees ) compared with the controls (80 +/- 12 degrees ). The gain between 0.1 Hz oscillations in blood pressure and cerebral blood flow velocity did not differ significantly between the patients and controls. CONCLUSIONS/INTERPRETATION: The reduced phase shift angle between oscillations in mean blood pressure and cerebral blood flow velocity during deep breathing suggests altered cerebral autoregulation in patients with diabetes and might contribute to an increased risk of cerebrovascular disorders.

Advanced electrocardiographic predictors of mortality in familial dysautonomia.

OBJECTIVE: To identify electrocardiographic predictors of mortality in patients with familial dysautonomia (FD). METHODS: Ten-minute resting high-fidelity 12-lead electrocardiograms (ECGs) were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict mortality over a subsequent 4.5-year period, including representative parameters of heart rate variability (HRV), QT variability (QTV), T-wave complexity, signal averaged ECG, and 3-dimensional ECG. RESULTS: Four of the 14 FD patients died during the follow-up period, three with concomitant pulmonary disorder. Of the ECG parameters studied, increased non-HRV-correlated QTV and decreased HRV were the most predictive of death. Compared to controls as a group, FD patients also had significantly increased ECG voltages, JTc intervals and waveform complexity, suggestive of structural heart disease. CONCLUSION: Increased QTV and decreased HRV are markers for increased risk of death in FD patients. When present, both markers may reflect concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea.

Altered cerebral regulation in type 2 diabetic patients with cardiac autonomic neuropathy.

AIMS/HYPOTHESIS: Assessment of cerebral regulation in diabetic patients is often problematic because of the presence of cardiac autonomic neuropathy. We evaluated the technique of oscillatory neck suction at 0.1 Hz to quantify cerebral regulation in diabetic patients and healthy control subjects. SUBJECTS AND METHODS: In nine type 2 diabetic patients with cardiac autonomic neuropathy and 11 age-matched controls, we measured blood pressure and cerebral blood flow velocity responses to application of 0.1 Hz neck suction. We determined spectral powers and calculated the transfer function gain and phase shift between 0.1 Hz blood pressure and cerebral blood flow velocity oscillations as parameters of cerebral regulation. RESULTS: In the patients and control subjects, neck suction did not significantly influence mean values of the RR interval, blood pressure and cerebral blood flow velocity. The powers of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations increased in the control subjects, but remained stable in the patients. Transfer function gain remained stable in both groups. Phase shift decreased in the patients, but remained stable in control subjects. CONCLUSIONS/INTERPRETATION: The absence of an increase in the power of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations confirmed autonomic neuropathy in the diabetic patients. Gain analysis did not show altered cerebral regulation. The decrease in phase shift in the patients indicates a more passive transmission of neck suction-induced blood pressure fluctuations onto the cerebrovascular circulation, i.e. altered cerebral regulation, in the patients, and is therefore suited to identifying subtle impairment of cerebral regulation in these patients.

Enhanced external counterpulsation does not compromise cerebral autoregulation.

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.

[Female sexual dysfunction: a systematic overview of classification, pathophysiology, diagnosis and treatment]. / Weibliche sexuelle Funktionsstörungen: Klassifikation, Diagnostik und Therapie.

Sexual dysfunction is defined as "disturbances in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty". The female sexual response cycle consists of three phases: desire, arousal, and orgasm. Various organs of the external and internal genitalia, e.g. vagina, clitoris, labia minora, vestibular bulbs, pelvic floor muscles and uterus, contribute to female sexual function. During sexual arousal, genital blood flow and sensation are increased. The vaginal canal is moistened (lubrication). During orgasm, there is rhythmical contraction of the uterus and pelvic floor muscles. Within the central nervous system, hypothalamic, limbic-hippocampal structures play a central role for sexual arousal. Sexual arousal largely depends on the sympathetic nervous system. Moreover, nonadrenergic/noncholinergic neurotransmitters (NANC), e.g. vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), are involved in smooth muscle relaxation and enhancement of genital blood flow. Furthermore, various hormones may influence female sexual function. Estrogen has a significant role in maintaining vaginal mucosal epithelium as well as sensory thresholds and genital blood flow. Androgens primarily affect sexual desire, arousal, orgasm and the overall sense of well-being. The internationally accepted classification of female sexual dysfunction consists of hypoactive sexual desire disorders, sexual aversion disorders, sexual arousal disorders, orgasmic disorders and sexual pain disorders. Vascular insufficiency, e.g. due to atherosclerosis, and neurologic diseases, e.g. diabetic neuropathy, are major causes of sexual dysfunction. Additionally, sexual dysfunction may be due to changes in hormonal levels, medications with sexual side effects or of psychological origin. For the diagnosis of female sexual dysfunction, a detailed history should be taken initially, followed by a physical examination and laboratory studies. Physiologic monitoring of parameters of arousal potentially allows to diagnose organic diseases. Recordings at baseline and following sexual stimulation are recommended to determine pathologic changes that occur with arousal. Duplex Doppler sonography, photoplethysmography or the measurement of vaginal and minor labial oxygen tension may help to evaluate genital blood flow. Moreover, measurements of vaginal pH and compliance should be performed. Neurophysiological examination, e.g. measurement of the bulbocavernosus reflex and pudendal evoked potentials, genital sympathetic skin response (SSR), warm, cold and vibratory perception thresholds as well as testing of the pressure and touch sensitivity of the external genitalia, should be performed to evaluate neurogenic etiologies. Medical management of female sexual dysfunction so far is primarily based on hormone replacement therapy. Application of estrogen results in decreased pain and burning during intercourse. The efficacy of various other medications, e.g. sildenafil, L-arginine, yohimbine, phentolamine, apomorphine and prostaglandin E1, in the treatment of female sexual dysfunction is still under investigation.

[Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and therapeutic concepts]. / Diabetische somatische Polyneuropathie. Pathogenese, klinische Manifestationsformen und Therapie-Konzepte.

Diabetic polyneuropathy is the most frequent neuropathy in western countries. In Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out other polyneuropathies and assess two out of the five diagnostic criteria: neuropathic symptoms, neuropathic deficits, pathological nerve conduction studies, pathological quantitative sensory testing and pathological quantitative autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to be fully understood. Among the various pathophysiological concepts are the Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the accumulation of Sorbitol and Fructose, the concept of deficiency of essential fatty acids with reduced availability of gamma-linolenic-acid and prostanoids, the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal dysfunction and structural lesions to increased oxidative stress and free radical production. Obviously, the hyperglycemia induced generation of advanced glycation end products (AGEs) also contributes to structural dysfunctions and lesions. Elevated levels of circulating immune complexes and activated T-lymphocytes as well the identification of autoantibodies against vagus nerve or sympathetic ganglia support the concept of an immune mediated neuropathy. The reduction of neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like growth factors also seems to further diabetic neuropathy. The symmetrical, distally pronounced and predominantly sensory neuropathy is far more frequent than the symmetrical neuropathy with predominant motor weakness or the asymmetrical neuropathy. The painless neuropathy manifests with impaired light touch sensation, position sense, vibratory perception and diminished or absent ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily affects small nerve fibers and accounts for decreased temperature perception and paresthesias. The proximal, diabetic amyotrophy evolves subacutely or acutely, induces motor weakness of the proximal thigh and buttock muscles and is painful. Cranial nerve III-neuropathy is also painful and has an acute onset. Truncal radiculopathy follows the distribution of truncal roots and frequently causes intense pain. Autonomic neuropathy occurs with and without somatic neuropathy. The most important therapy is to attempt optimal blood glucose control, to reduce body weight and hyperlipidemia. Symptomatic therapy includes alpha-lipoic acid treatment, as the antioxidant seems to improve neuropathic symptoms. Aldose reductase inhibitors might reduce sorbitol and fructose production and normalize myo-inositol levels. However, there are no aldose reductase inhibitors available in Europe as yet. Evening primrose oil, containing gamma-linolenic acid, might improve nerve conduction velocities, temperature perception, muscle strength, tendon reflexes and sensory function. Substitution of nerve growth factor showed promising results in pilot studies but failed in a large-scale multicenter study. Symptomatic pain treatment can be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, anticonvulsants such as carbamazepine, gabapentin or lamotrigine, or anti-arrhythmic drugs such as mexiletine. Topical capsaicin application should reduce neuropathic pain but also induces local discomfort in the beginning of therapy. Vasoactive substances, so far have not proven to be of major benefit in diabetic neuropathy. Physical therapy and thorough footcare are of primary importance and allow prevention of secondary complications such as foot amputations.

[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management]. / Synkopen - eine systematische Ubersicht zur Klassifikation, Pathogenese, Diagnostik und Therapie.

Syncope is defined as a temporary interruption of cerebral perfusion with a sudden and transient loss of consciousness and spontaneous recovery. Approximately one third of the population experiences syncope at least once during a lifetime. Presyncopal signs and symptoms, including weakness, headache, blurred vision, diaphoresis, nausea, and vomiting are sometimes present for seconds or minutes prior to loss of consciousness. After syncope, the patients may present with persisting drowsiness, headache, dizziness, nausea, but not usually confusion. Causes of syncope have been categorized as cardiovascular, non-cardiovascular, and unexplained. Cardiovascular causes can be subdivided into structural heart disease, coronary heart disease, and arrhythmia. Non-cardiovascular causes include neurological, metabolic, psychiatric and other disorders.Orthostatic hypotension - one of the most frequent causes of syncope - has manifold etiologies comprising various neurological and internal diseases. Orthostatic hypotension usually can be attributed to an impairment of peripheral vasoconstriction or to a reduction of the intravascular volume. Signs and symptoms, including the above prodromi are often present just after rising from a supine or sitting position. Frequently, blood pressure decreases significantly without an increase in heart rate. Autonomic cardiovascular modulation is often reduced. Many of the patients with "unexplained" syncope experience neurally mediated (i. e. neurocardiogenic or vasovagal) syncope. In these patients, cardiovascular control may be stable for an extended period of time during orthostatic stress, then there is a sudden decrease in blood pressure and heart rate. Neurocardiogenic or neurally mediated syncope can be associated with painful or emotionally stressful situations such as anxiety or fear, with prolonged standing or specific trigger situations such as micturition, defecation, coughing or sneezing, visceral or carotid sinus stimulation, or with trigeminal or glossopharyngeal neuralgia. So far, the mechanisms of neurocardiogenic syncope are not completely understood. The passive 60 degrees to 70 degrees head-up tilt test is useful for the diagnosis of orthostatic and neurally mediated syncope. The sensitivity of the test can be improved by additional pharmacological provocation, e. g. by isoproterenol, or by increased orthostatic stress using lower body negative pressure stimulation. For the treatment of syncope one should first consider non-pharmacological options. Patients with orthostatic hypotension should avoid rapid changes of the body position from supine to standing, as well as high room temperature or other situations inducing peripheral vasodilatation. An increased intake of sodium and fluids, mild physical exercise or so-called postural counter-maneuvers can improve orthostatic tolerance. Among the drugs recommended for pharmacologic treatment are mineralocorticoids (e. g. fludrocortisone), vasoconstrictor agents (e. g. ephedrine, midodrine), adenosine receptor blockers (theophylline) and beta2-blockers (propanolol), anticholinergic agents, e. g. scopolamine or disopyramide, and negative cardiac inotropes, e. g. beta1-adrenergic blockers or disopyramide. Serotonin reuptake inhibitors (e. g. fluoxetine, sertraline), alpha2-adrenergic agonists (clonidine), central nervous system stimulants such as methylphenidate or phentermine are thought to be beneficial in specific cases. Cardiac pacemakers often seem to be recommended without adequate indication. The antidiuretic, V2-receptor specific, vasopressin analogue desmopressin increases the intravascular volume. Erythropoietin improves anemia and red blood cell decrease and augments blood pressure and cerebral oxygenation. In postprandial hypotension, octreotide, a somatostatin analogue, prostaglandin inhibitors such as indomethacin or ibuprofen, as well as metoclopramide or two cups of coffee per day might be beneficial.

Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy.

BACKGROUND: Peripheral neuropathy in Fabry disease predominantly involves small nerve fibers. Recently, enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A has become available. OBJECTIVE: To evaluate whether ERT improves Fabry neuropathy. METHODS: In 22 Fabry patients (age 27.9 +/- 8.0 years) undergoing ERT with recombinant human alpha-galactosidase A (agalsidase beta) for 18 (n = 11) or 23 (n = 11) months and in 25 control subjects (age 29.0 +/- 10.4 years), the authors performed quantitative sensory testing using the 4, 2, and 1 stepping algorithm (CASE IV). Detection thresholds of vibration (VDT) on the first toe were assessed; cold detection thresholds (CDT), heat-pain onset (HP 0.5), and intermediate heat-pain (HP 5.0) assessments were made on the dorsum of the feet. Patient values above mean + 2.5 SD of control values were considered abnormal. RESULTS: Before ERT, VDT, CDT, HP 0.5, and HP 5.0 were higher in patients than control subjects (p < 0.05). Following ERT, patients developed lower thresholds than prior to ERT for VDT (15.5 +/- 3.5 vs 14.3 +/- 4.1; p < 0.05), HP 0.5 (22.3 +/- 6.7 vs 19.4 +/- 1.3; p < 0.01), and HP 5.0 (27.3 +/- 5.6 vs 22.5 +/- 2.3; p < 0.01). Moreover, fewer patients had abnormal results of VDT (2 vs 4), CDT (7 vs 12), HP 0.5 (0 vs 9), and HP 5.0 (4 vs 20) after than before ERT. CONCLUSIONS: 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.

Sudomotor function in familial dysautonomia.

BACKGROUND: Patients with familial dysautonomia (FD) manifest episodic hyperhidrosis despite the reduction of sudomotor fibres and sweat glands associated with this autonomic neuropathy. We assessed peripheral sudomotor nerve fibre and sweat gland function to determine if this symptom was due to peripheral denervation hypersensitivity. METHODS: In 14 FD patients and 11 healthy controls, direct and axon reflex mediated sweat responses were determined by measuring transepidermal water loss (TEWL) after application of acetylcholine via a microdialysis membrane, a novel method to evaluate sudomotor function in neuropathy patients. Results were compared with data from conventional quantitative sudomotor axon reflex testing (QSART). Using microdialysis, interstitial fluid was analysed for plasma proteins to evaluate protein extravasation induced by acetylcholine as an additional parameter of C-fibre function. RESULTS: Although reduced axon reflex sweating was expected in FD patients, neither direct or axon reflex mediated sweat responses, nor acetylcholine induced protein extravasation differed between control and patient groups. However, the baseline resting sweat rate was higher in FD patients than controls (p<0.05). TEWL and QSART test results correlated (r = 0.64, p = 0.01), proving the reliability of TEWL methodology in evaluating sudomotor function. CONCLUSION: The finding of normal direct and axon reflex mediated sweat output in FD patients supports our hypothesis that, in a disorder with severe sympathetic nerve fibre reduction, sudomotor fibres, but not the sweat gland itself, exhibit chemical hypersensitivity. This might explain excessive episodic hyperhidrosis in situations with increased central sympathetic outflow.

Enhanced external counterpulsation improves skin oxygenation and perfusion.

BACKGROUND: Enhanced external counterpulsation (EECP) augments diastolic and reduces systolic blood pressures. Enhanced external counterpulsation has been shown to improve blood flow in various organ systems. Beneficial effects on skin perfusion might allow EECP to be used in patients with skin malperfusion problems. This study was performed to assess acute effects of EECP on superficial skin blood flow, transdermal oxygen and carbon dioxide pressures. MATERIALS AND METHODS: We monitored heart rate, blood pressure, transdermal blood flow as well as oxygen and carbon dioxide pressures in 23 young, healthy persons (28 +/- 4 years) and 15 older patients (64 +/- 7 years) with coronary artery disease before, during and 3 min after 5 min EECP. Friedman test was used to compare the results of 90-s epochs before, during and after EECP. Significance was set at P < 0.05. RESULTS: Enhanced external counterpulsation increased heart rate and mean blood pressure. During EECP, transdermal oxygen pressure and concentration of moving blood cells increased while transdermal carbon dioxide pressure and velocity of moving blood cells decreased significantly in both groups. After EECP, transdermal carbon dioxide pressure was still reduced while the other parameters returned to baseline values. CONCLUSIONS: Improved skin oxygenation and carbon dioxide clearance during EECP seem to result from the increased concentration and reduced flow velocity, i.e. prolonged contact time, of erythrocytes. The increased concentration of moving blood cells and the decreased velocity of moving blood cells at both tested skin sites indicate peripheral vasodilatation.

Dermal microdialysis provides evidence for hypersensitivity to noradrenaline in patients with familial dysautonomia.

OBJECTIVES: To use the technique of dermal microdialysis to examine sensitivity of skin vessels to noradrenaline (NA) in patients with familial dysautonomia (FD) and in healthy controls. METHODS: In 14 patients with FD and 12 healthy controls, plasma extravasation, local laser Doppler blood flow, and skin blanching were observed before, during, and after application of 10(-6) M NA through a microdialysis membrane, located intradermally in the skin of the lower leg. RESULTS: Maximum local vasoconstriction measured by laser Doppler blood flow did not differ between patients with FD and controls. In contrast, patients with FD had an earlier onset of vasoconstriction (p = 0.02). Moreover, reaction to NA was more prominent and prolonged in FD, shown by a larger zone of skin blanching around the microdialysis membrane (p < 0.001) and delayed reduction of the protein content in the dialysate after termination of NA application (p = 0.03). CONCLUSION: These data support the hypothesis that peripheral blood vessels of patients with FD show a denervation hypersensitivity to catecholamines. This may be one mechanism contributing to the major hypertension that frequently occurs during "dysautonomic crises" in FD.

Changes of cerebral blood flow velocities during enhanced external counterpulsation.

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.

Oral mucosal blood flow following dry ice stimulation in humans.

The aim of the current pilot study was to establish a procedure that would allow the investigation of microcirculatory changes in the oral cavity. The authors studied the effects of painful stimulation using dry ice (CO2). To investigate potential regional differences in the change of blood flow, recordings were made for the tongue and at the mucosa of the hard palate, lip, and oral vestibule. The authors investigated 26 patients divided into groups of younger subjects (10 men, 3 women; age range 21-31 y) and older patients (2 men, 11 women; age range 54-74 y). Mucosal blood flow (mBF) was obtained at the hard palate, at the tip of the tongue, on the midline of the oral vestibule, and at the lip. Measurements were made during rest and for 2 minutes after application of dry ice for a 10-second duration, using a pencil-shaped apparatus. Blood pressure, heart rate, cutaneous blood flow, transcutaneous partial pressure of carbon dioxiode (PCO2) and partial pressure of oxygen (PO2) were recorded. Mucosal blood flow increased at all sites in response to application of dry ice (p <0.001), with peak flow at 0.5 minute to 1.5 minutes after onset of stimulation. During the 1.5 minutes to 2 minutes, blood flow decreased at all measurement sites with a tendency to return to baseline. Heart rate, blood pressure, pCO2, PO2, and cutaneous blood flow did not show significant changes. Overall, responses in older patients showed more variance when compared with younger patients. Stimulation by dry ice appears to be an effective, noninvasive, and tolerable means to investigate mucosal blood flow at different mucosal sites. Preliminary data indicate different levels of responsiveness to painful cold stimulation at different sites on the oral and perioral mucosa; particularly, mucosal blood flow response at the tongue was least pronounced. Therefore, assessment of stimulated mucosal blood flow appears to be a promising tool to investigate the pathophysiology of a number of neurologic symptoms, eg, the burning mouth syndrome.

Myogenic cerebrovascular autoregulation in migraine measured by stress transcranial Doppler sonography.

BACKGROUND AND PURPOSE: Transcranial Doppler sonography (TCD) studies may help to elucidate the nature and role of vascular abnormalities in migraine. Our aim in this study was to evaluate cerebrovascular autoregulative response in migraine patients with and without aura to blood pressure increase using stress TCD. PATIENTS AND METHODS: Using transcranial Doppler ultrasound at rest and during ergometer stress (stress TCD), we studied the changes in mean flow velocities and resistance index (RI) in relation to physical stress in the middle cerebral artery. Fifteen migraine patients without aura, 15 migraine patients with aura, and 15 healthy control subjects were examined. Patients suffered from predominantly unilateral headache and were studied during an attack-free period. The Pourcelot's RI as a measure of cerebrovascular reactivity was calculated by dividing the difference between systolic and diastolic velocity by the systolic velocity. RESULTS: None of the subgroups showed any difference during ergometer exercise with regard to blood pressure, endtidal CO2, heart rate, or mean flow velocity. In all subgroups, sufficient physical stress was achieved. With respect to RI change, migraine patients without aura and healthy controls did not differ (p > 0.05). However, the RI change of migraine patients with aura was significantly lower than the RI change of migraine patients without aura or healthy subjects (p > 0.05). The discrimination analysis showed in addition that RI change (absolute and as a percentage) and mean flow velocity change (as a percentage) could be used as diagnostic variables to detect patients with aura symptoms. CONCLUSION: Differences exist in cerebrovascular reactivity in migraine patients with aura that may contribute to the neurologic disturbances in these patients during attack. We propose that there is disorder of myogenic cerebrovascular autoregulation in migraine patients with aura during headache-free intervals.

Clonidine improves postprandial baroreflex control in familial dysautonomia.

BACKGROUND: Patients with familial dysautonomia (FD) frequently experience hypertensive crises after gastrostomy feeding. The central alpha2-agonist clonidine attenuates feeding-induced crises. The aim of this study was to assess the effect of clonidine on cardiovascular autonomic modulation and particularly baroreflex sensitivity in familial dysautonomia after gastrostomy feeding. MATERIAL AND METHODS: In nine patients, we monitored the RR-interval and systolic blood pressure at supine rest before (baseline 1) and after gastrostomy feeding (GF1). One day later, recordings were repeated after clonidine intake (baseline 2, GF2). We determined spectral powers of RR-interval and systolic blood pressure in the low- (LF) and high-frequency range (HF). Sympathovagal balance was determined from the LF/HF ratio of RR-interval. Baroreflex sensitivity was assessed from the alpha-index of systolic blood pressure and RR-interval. RESULTS: Gastrostomy feeding decreased RR-interval, while systolic blood pressure remained stable. Clonidine induced higher RR-intervals before and after gastrostomy feeding but decreased systolic blood pressure at baseline only. Gastrostomy feeding decreased HF-power of RR-interval significantly without clonidine, but only slightly after premedication. Clonidine increased the HF-power of RR-interval slightly at baseline and significantly after gastrostomy feeding. Gastrostomy feeding increased the LF/HF ratio without clonidine only. Clonidine decreased the LF/HF ratio at baseline and after gastrostomy feeding. Gastrostomy feeding did not change baroreflex sensitivity, but baroreflex sensitivity was higher at visit 2 than visit 1. CONCLUSIONS: In familial dysautonomia, clonidine augments baroreflex sensitivity and parasympathetic modulation. The resulting cardiovascular stabilization might attenuate feeding-induced crises.