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Biomedical subjects

S Braune

Publications and source records attributed to S Braune.

At least 19 recordsLinked to original sources

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

Adolescent↗

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.

Acoustic Stimulation↗

[Evidence-based pharmacotherapy of neuropathic pain syndromes].

Neuropathic pain can severely reduce quality of life. Double blind, placebo controlled studies confirm the efficacy of the treatment of painful neuropathy, postherpetic neuralgia and trigeminal neuralgia with tricyclic antidepressants, ion channel blockers, opioids and lipoic acid. The numbers-needed-to-treat (NNT) with monotherapy to achieve pain reduction of at least 50% are in the range of 2 to 4. Recent studies indicate that patients can benefit from combinations of opioids and tricyclic antidepressants or opioids and gabapentin.

Amines↗

Challenging cerebral autoregulation in patients with preganglionic autonomic failure.

Intact cerebral autoregulation is essential to prevent cerebral hypoperfusion during pronounced changes in arterial blood pressure (ABP) in patients with autonomic failure (AF). It is still a matter of debate whether and to what extent cerebral autoregulation is disturbed in these patients. This study evaluates the interaction between cerebral blood flow velocity (CBFV) and ABP during Valsalva maneuver (VM) and tilt-table testing in nine patients with multiple system atrophy including AF and in 14 age-matched controls. CBFV and ABP were recorded noninvasively using transcranial Doppler sonography and the Finapres device. Responses to VM were graded by the autoregulation slope index (ASI). Cerebrovascular resistance changes were estimated by the conventional ratio ABP/CBFV and by the dynamic pressure-velocity relationship. To challenge cerebral autoregulation further, tests were repeated under hypercapnic predilation of cerebral arterioles. During VM, CBFV reincreased in patients despite a pronounced ABP drop and showed an overshoot after the strain, thus, being similar to controls. The ASI was higher in patients than in controls ( p < 0.05). During 70 degrees head-up tilt, ABP dropped markedly, but the decrease in CBFV was small and did not differ significantly from controls. In patients, both tests were associated with a substantial decrease of the dynamic but not of the conventional pressure-velocity relationship. Under hypercapnia, the CBFV response in patients remained unchanged. We conclude that 1). cerebral arterioles have the capacity for adequate vasodilation during ABP drops in patients with AF and that this ability is still present under hypercapnic predilation. 2). The mechanism of cerebral autoregulation in itself does not seem to be affected by the AF but is rather well exercised. 3) The VM presents, in addition to tilt-table testing, a simple test for clinical evaluation of cerebral autoregulation in patients with AF.

Aged↗

Need and use of psychotherapeutic interventions within a psychosomatic liaison service in neurology.

OBJECTIVES: The study addresses the evaluation of psychosocial distress, the need for care as determined by a psychotherapist and patients, and the realization of psychotherapeutic interventions within a routine psychosomatic liaison service. MATERIAL AND METHODS: A total of 84 patients from one unit at the Department of Neurology of the University of Freiburg, Germany, underwent a structured psychodiagnostic interview and filled out self-rating instruments to evaluate mental disorders, psychosocial distress, ways of coping strategies and quality of life. The need for treatment and the motivation of patients were estimated by both patients and a liaison psychotherapist. RESULTS: Using ICD-10-F criteria, mental and behavioral disorders were diagnosed in 35% of cases. Professional assessment indicated a need for psychotherapeutic treatment in 37% of patients; actual intervention occurred in 27%. Only slight agreement was found between the estimated need for treatment and the interventions actually performed. CONCLUSIONS: The realization of psychotherapeutic interventions is subject to a complex interaction between the needs of a patient, the "objective" psychosocial distress of the patient, and institutional factors. About 10% of the hospitalized patients considered in the study need continuous psychotherapeutic treatment.

Adult↗

AMOG/beta2 and glioma invasion: does loss of AMOG make tumour cells run amok?

The beta2 subunit of Na,K-ATPase, initially described as adhesion molecule on glia (AMOG), has been shown to mediate neurone-astrocyte adhesion as well as neural cell migration in vitro. We have investigated the expression of AMOG/beta2 in human gliomas and its effect on glioma cell adhesion and migration. Compared to normal astrocytes of human brain, AMOG/beta2 expression levels of neoplastic astrocytes were down-regulated in biopsy specimens and inversely related to the grade of malignancy. One rat and four human glioma cell lines showed complete loss of AMOG. To investigate the function of AMOG/beta2, its expression was re-established by transfecting an expression plasmid into AMOG/beta2-negative C6 rat glioma cells. In vitro assays revealed increased adhesion and decreased migration on matrigel of AMOG/beta2-positive cells as compared to their AMOG/beta2-negative counterparts. We conclude that increasing loss of AMOG/beta2 during malignant progression parallels and may underlie the extensive invasion pattern of malignant gliomas.

Adenosine Triphosphatases↗

Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma.

A 68-year-old man presented with general fatigue, increasing adynamia, weakness, vertigo and recurrent syncope. Six weeks earlier the diagnosis of a macroprolactinoma had been established based on a greatly elevated prolactin concentration (161 170 micro U/l) and MR-evidence of a 3.5 cm measuring pituitary mass. The patient had been started on cabergoline (1.5 mg weekly). Orthostatic hypotension due to the dopamine agonist was considered very likely and carbergoline therapy was stopped. However, there was no relief of the symptoms and further syncopes followed. Testing of blood pressure and heart rate regulation, selective testing of postganglionic cardiac neurons with [ 123 J] metaiodobenzylguanidine scintigraphy provided evidence of grossly impaired neurogenic cardiovascular regulation due to failure of postganglionic efferent sympathetic activity. This is characteristic for pure autonomic failure. The patient was treated symptomatically with high fluid intake, compression stockings, fludrohydrocortisone (0.1 mg o.d.s.), piroxicam (20 mg o.d.s.) and etilephrin (10 mg q.d.s.), which enabled him to cope with daily activities without syncope. This case shows that vertigo in a patient with macroprolactinoma is not always related to drug therapy but may be related to other causes.

Adrenergic Agonists↗

Influence of a radiofrequency electromagnetic field on cardiovascular and hormonal parameters of the autonomic nervous system in healthy individuals.

The potential health risks of radiofrequency electromagnetic fields (EMFs) emitted by mobile phones are of considerable public interest. The present study investigated the hypothesis, based on the results of our previous study, that exposure to EMFs can increase sympathetic vasoconstrictor activity. Forty healthy young males and females underwent a single-blind, placebo-controlled protocol once on each of two different days. Each investigation included successive periods of placebo and EMF exposure, given in a randomized order. The exposure was implemented by a GSM-like signal (900 MHz, pulsed with 217 Hz, 2 W) using a mobile phone mounted on the right-hand side of the head in a typical telephoning position. Each period of placebo exposure and of EMF exposure consisted of 20 min of supine rest, 10 min of 70 degrees upright tilt on a tilt table, and another 20 min of supine rest. Blood pressure, heart rate and cutaneous capillary perfusion were measured continuously. In addition, serum levels of norepinephrine, epinephrine, cortisol and endothelin were analyzed in venous blood samples taken every 10 min. Similar to the previous study, systolic and diastolic blood pressure each showed slow, continuous, statistically significant increases of about 5 mmHg during the course of the protocol. All other parameters either decreased in parallel or remained constant. However, analysis of variance showed that the changes in blood pressure and in all other parameters were independent of the EMF exposure. These findings do not support the assumption of a nonthermal influence of EMFs emitted by mobile phones on the cardiovascular autonomic nervous system in healthy humans.

Adult↗

The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of parkinsonian syndromes.

Scintigraphy with radiolabeled metaiodobenzylguanidine (MIBG) enables the visualization and quantification of functionally intact adrenergic neurons and cells. In Parkinson disease, MIBG uptake of postganglionic cardiac sympathetic neurons is grossly reduced at an early stage of the disease in almost all patients with a clinical severity score of Hoehn and Yahr II or higher. Based on the meta-analysis of studies with a total of 246 cases of Parkinson disease and 45 cases of multiple system atrophy, the overall sensitivity to positively identify patients with Parkinson disease was 89.7%, and the specificity to discriminate them from patients with multiple system atrophy was 94.6%. Quantification of cardiac MIBG uptake is a valuable tool to identify patients with Parkinson disease and to discriminate them from other neurodegenerative disorders early in the course of the disease.

3-Iodobenzylguanidine↗

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Adolescent↗

Multiple system atrophy: pathophysiology and management.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that usually manifests when an individual is in his/her early fifties and progresses relentlessly with a mean survival of 9 years. Clinically, MSA is dominated by autonomic/urogenital failure which may be associated with either parkinsonism (MSA-P subtype) in 80% of cases or with cerebellar ataxia (MSA-C subtype) in 20% of cases. Pathologically, MSA is characterised by a neuronal multisystem degeneration and abnormal glial cytoplasmic inclusions containing alpha-synuclein aggregates. Autonomic and urogenital features of MSA should be identified early on because they can be treated effectively in many instances. In contrast, pharmacological treatment of motor features is often disappointing, except for a minority of patients with MSA-P who derive transient benefit from levodopa treatment. In the future, neurotransplantation may extend or improve the treatment response in MSA-P, but further preclinical evidence is required prior to clinical application. Neuroprotection strategies may slow down disease progression in MSA and the results of the first double-blind trial of riluzole (an inhibitor of glutamate release) in patients with MSA will be available in 2004.

Animals↗

Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake.

Primary dysfunction of the autonomic nervous system can be observed in patients with Parkinson's disease and those with multiple system atrophy. However, the fate of the two diseases differs considerably and leads to different strategies for patient management. Differentiation of the two diseases currently requires a combination of several clinical and electrophysiological tests. First studies of myocardial innervation using iodine-123 metaiodobenzylguanidine (MIBG) indicated a possible role of scintigraphy for this purpose. An increase in the pulmonary uptake of 123I-MIBG has been reported in secondary dysautonomias. Whether sympathetic innervation of the lung is affected in primary dysautonomias is currently unknown. Therefore, cardiac and pulmonary uptake of 123I-MIBG was studied in 21 patients with Parkinson's disease, 7 patients with multiple system atrophy and 13 age- and sex-matched controls. Thoracic images were obtained in the anterior view 4 h after intravenous injection of 185 MBq 123I-MIBG, at which time the maximum neuronal uptake is reached. All patients with Parkinson's disease had significantly lower cardiac uptake of 123I-MIBG than patients with multiple system atrophy and controls. Sympathetic innervation of the lung was not affected in either disease. It is concluded that scintigraphy with 123I-MIBG appears to be a useful tool for differentiation between Parkinson's disease and multiple system atrophy early after onset of autonomic dysfunction.

3-Iodobenzylguanidine↗

Cardiac uptake of [123I]MIBG separates Parkinson's disease from multiple system atrophy.

OBJECTIVE: To improve the differential diagnosis between patients with multiple system atrophy (MSA) and idiopathic PD (IPD) with autonomic failure. BACKGROUND: Some patients diagnosed with IPD are discovered to have alternative diseases such as MSA, despite the application of stringent diagnostic criteria. This differentiation is particularly difficult if patients with IPD also show symptoms of autonomic failure. In IPD, autonomic failure is caused by damage of the postganglionic part of the autonomic nervous system, whereas in MSA, degeneration of preganglionic and central autonomic neurons is revealed histopathologically. METHODS: Scintigraphy with [123I]metaiodobenzylguanidine (MIBG) enables the quantification of postganglionic sympathetic cardiac innervation. Fifteen patients with IPD and 5 patients with MSA underwent standard autonomic function tests and scintigraphy with MIBG. RESULTS: In all patients, cardiovascular testing showed evidence of autonomic failure of varying severity. In all patients with IPD, the heart-mediastinum (H/M) ratio of MIBG uptake was pathologically impaired, independent of duration and severity of autonomic and parkinsonian symptoms. All patients with MSA had a regular H/M ratio. Each patient could be assigned to the correct diagnostic group based on the results of the MIBG scintigraphy, even if the duration of the disease was only 2 years or less. CONCLUSIONS: This population assessment of the heart-mediastinum ratio of [123I]metaiodobenzylguanidine uptake showed a high sensitivity for the detection of autonomic involvement in patients with idiopathic IPD and also a high specificity for the discrimination between idiopathic PD and MSA.

3-Iodobenzylguanidine↗

Quantitative sudomotor axon reflex test (QSART): a new approach for testing distal sites.

The quantitative sudomotor axon reflex test (QSART) is a useful tool in the evaluation of C-fiber function. Because many neuropathies show a length-dependent loss of nerve function, a new capsule was designed for distal performance of the QSART, allowing measurements on fingers and toes. We investigated 20 healthy volunteers and 15 patients with insulin-dependent diabetes mellitus and normal sensory nerve conduction studies. A QSART was performed on the forearm and on the thumb. The groups showed no differences in the QSARTs on the forearm, but the sweat volume on the thumb was significantly lower in patients. Calculation of the forearm/finger ratio reduced the interindividual variation and showed the highest sensitivity for detecting C-fiber dysfunction in the patient group. We conclude that the distal measuring device and the forearm/finger ratio are more sensitive tools for the early detection of distal-onset neuropathies than are the commonly used proximal testing sites.

Adult↗

Diagnosis of tachycardia syndromes associated with orthostatic symptoms.

The postural tachycardia syndrome (POTS) is characterized by excessive tachycardia only in upright position without evidence of a cardiac or metabolic disease in combination with orthostatic symptoms like dizziness, lightheadedness or syncope but without relevant falls in blood pressure. The cause is unknown. A specific diagnostic marker has not been found so far. Eighteen patients with typical symptoms of POTS were examined. They underwent standard autonomic function tests with continuous measurement of heart rate (HR) and blood pressure. All fulfilled the inclusion criteria of pathologically increased HR activation during passive tilt or standing over 90 seconds. The upper limits of normal were based on data from 137 healthy volunteers between 18 and 85 years of age. Actively standing up induced more POTS-typical HR increases and lead to more consistent results than passive tilt. HR responses during Valsalva manoeuvre and deep breathing were normal in all except one patient each, indicating that assessment of HR during these tests does not contribute to the diagnosis of POTS. Frequency of symptoms reducing overall well-being and the degree of impairment of life quality by symptoms typical of POTS were measured with a self-assessment scale. The majority of patients reported a permanent reduction of overall well-being and a relevant impairment of life quality due to dizziness, tachycardia, and syncopes. This underlines the importance of considering POTS as a differential diagnosis of orthostatic syndromes and the necessity of treating it adequately.

Adolescent↗

Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.

Adult↗

CO2 reactivity testing without blood pressure monitoring?

BACKGROUND AND PURPOSE: Responsiveness to CO2 is an established test of cerebrovascular reserve capacity. Arterial partial pressure of CO2 (PCO2) and arterial blood pressure (BP) are key parameters for cerebral blood flow. To investigate the interaction between PCO2 and BP, we performed a study with simultaneous measurement of CO2 and BP during CO2 reactivity testing with transcranial Doppler sonography. METHODS: Eighty-one healthy volunteers, aged 19 to 74 years, underwent examination defined by a protocol with multimodality monitoring of BP, heart rate (HR), PCO2, and Doppler frequencies (DFs) of the left middle cerebral artery (MCA). Reproducibility was tested in a subgroup of 14 volunteers >/=65 years of age by CO2 reactivity testing on different days. RESULTS: Increase of PCO2 was accompanied by a parallel increase of mean+/-SD time values of DF (3. 6+/-1.6%/mm Hg CO2). BP levels were significantly elevated after 60-second hypercapnia (mean values, 0.5+/-0.55 mm Hg/mm Hg CO2). A significant decrease over time was seen only for pulsatility in DF but not in BP. Analysis of variance and covariance with repeated measures revealed a highly significant effect of CO2 on MCA Doppler shift. A less-pronounced effect on DF was seen for BP. Correlation analysis showed no significance for CO2 reactivity, but a significant correlation between test and retest was seen in BP-related CO2 reactivity. CONCLUSIONS: The CO2 response curve showed the known linear increase of DF. The parallel significant increase in BP most likely results from activation of the central sympathetic nervous system. The poor reproducibility for Doppler CO2 reactivity is to some extent explainable by variability of BP. CO2-induced increases in BP can have relevant influence on MCA Doppler shift and lead to misinterpretation of Doppler CO2 test results.

Adult↗