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Biomedical subjects

Bernhard Neundörfer

Publications and source records attributed to Bernhard Neundörfer.

At least 19 recordsLinked to original sources

Increased hypoxic blood pressure response in patients with amyotrophic lateral sclerosis.

OBJECTIVES: There is evidence of impaired cardiovascular autonomic control and reduced baroreflex sensitivity in patients with amyotrophic lateral sclerosis (ALS). A compromised baroreflex-chemoreflex interaction might result in inadequate responses to chemoreflex activation with progressive hypercapnia and hypoxia and contribute to early fatalities. This study was performed to assess cardiovascular and ventilatory responses to hypercapnic and hypoxic stimulation in ALS patients with impaired baroreflex function. PATIENTS AND METHODS: In 15 ALS patients with previously demonstrated baroreflex dysfunction and in 15 age-matched controls, we compared electrocardiographic RR-interval (RRI), systolic blood pressure (SBP) and minute ventilation (VE) during normal ventilation and during selective progressive hypoxia and hypercapnia. RESULTS: Ventilatory and RRI responses to hypoxic and hypercapnic stimulation as well as SBP responses to hypercapnia did not differ between patients and controls. In contrast, hypoxia induced a significant SBP increase in patients only. CONCLUSIONS: The normal ventilatory and RRI responses to chemoreflex activation suggest intact afferent chemoreflex function. The hypertensive response to hypoxia might be due to a compromised interaction with the baroreflex. Avoiding hypoxic episodes might reduce the risk of cardiovascular crisis in ALS patients.

Adult↗

Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ, P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family.

Charcot-Marie-Tooth disease type 1B (CMT 1B) is caused by mutations in the gene coding for peripheral myelin protein zero (MPZ, P0) that plays a fundamental role in adhesion and compaction of peripheral myelin. Here we report a Costa Rican family with a hereditary peripheral neuropathy due to a novel Tyr145Ser MPZ mutation. Four family members were heterozygously affected; two siblings of two heterozygous carriers were homozygous for this mutation. On neurological examination the heterozygous parents and their homozygous children both showed distal sensory deficits. The mother and the siblings displayed impaired deep tendon reflexes and mild sensory ataxia. The homozygous individuals were more severely affected with an earlier age of onset, distal motor weakness, and pupillary abnormalities. Electrophysiological studies revealed both signs of demyelination and axonal nerve degeneration. The sural nerve biopsy of one sibling showed thinly myelinated nerve fibers, onion bulb formation, and clusters of regenerating fibers. On electron microscopy axonal degeneration and decompaction of inner myelin layers were found. This Costa Rican family shows phenotypic variability depending on the homozygous or heterozygous state of the Tyr145Ser mutation carriers.

Charcot-Marie-Tooth Disease↗

Cortical processing of brush-evoked allodynia.

The cortical processing of allodynia (touch-evoked pain) resulting from neuralgia of the lateral cutaneous femoral nerve was investigated with a newly designed pneumatically driven brush by means of magnetoencephalography. Brushing the unaffected thigh produced subsequent activation of the contralateral primary somatosensory cortex (S1) with peak latencies of 37 and 56 ms. Brushing the affected side led to comparable activation of the contralateral S1 cortex. In addition, the magnetic fields were stronger, and the corresponding equivalent current dipoles were located more laterally, consistent with the presence of cortical reorganisation. Allodynia was also accompanied by an activation of the cingulate cortex, occurring only 92 ms. after stimulus onset, an observation suggesting an Abeta-fiber-mediated neuronal pathway involved in dynamic mechanical allodynia. This study corroborates the concept of cortical reorganisation underlying chronic pain. Furthermore, it demonstrates that a remarkable early activation of the cingulate cortex may be involved in the cortical processing of allodynia.

Cerebral Cortex↗

Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation.

The aim of this study was to determine whether lower body negative pressure (LBNP), combined with noninvasive methods of assessing changes in systemic and cerebral vascular resistance, is suitable as a method for assessing cerebral autoregulation. In 13 subjects we continuously assessed heart rate, blood pressure, cerebral blood flow velocity (CBFV) and cardiac output during graded levels of LBNP from 0 to -50 mm Hg. With increasing levels of LBNP, cardiac output declined significantly (to 55.8+/-4.5% of baseline value) but there was no overall change in mean arterial pressure. CBFV also fell at higher levels of LBNP (to 81.4+/-3.2% of baseline) but the percentage CBFV change was significantly less than that in cardiac output (P<0.01). The maximum increase in cerebrovascular resistance (pulsatility ratio) was significantly less than that in total peripheral resistance (17+/-6% vs. 105+/-16%, P<0.01). Spectral analysis showed that the power of low-frequency oscillations in mean arterial pressure, but not CBFV, increased significantly at the -50 mm Hg level of LBNP. These results show that, even during high levels of orthostatic stress, cerebral autoregulation is preserved and continues to protect the cerebral circulation from changes in the systemic circulation. Furthermore, assessment of cardiovascular and cerebrovascular parameters during LBNP may provide a useful clinical test of cerebral autoregulation.

Adult↗

Emergency calls in acute stroke.

BACKGROUND AND PURPOSE: In the last 10 years, stroke has become a medical emergency. Subsequently, early recognition of stroke symptoms and rapid activation of the medical system are essential. We sought to investigate what witnesses or victims of an acute stroke syndrome recognize and report in the actual situation. METHODS: We analyzed the recordings of all patients admitted to our stroke unit via the Emergency Medical System (EMS) dispatch center in Nuremberg within 1 year. With a structured evaluation form, the calls were screened for symptoms reported and for any diagnosis or other facts mentioned spontaneously or in response to a question by the dispatcher. We also evaluated data about EMS response and patient condition on admission. RESULTS: Of 482 patients treated in our stroke unit, 141 calls were evaluated. Main symptoms reported included speech problems (25.5%), motor deficits (21.9%), and disturbances of consciousness (14.8%). In many cases, a fall (21.2%) was presented as the main problem. Sensory deficits (7.8%) and vertigo (5.6%) were rarely mentioned. In 28 calls (19.8%), stroke was mentioned as a possible cause of the acute health problems. The dispatcher suspected a stroke in 51.7% of all cases. CONCLUSIONS: This is one of the first studies to investigate emergency calls in acute stroke. We found that motor deficits and speech problems were the most dramatic symptoms that led to activation of the EMS. Other symptoms were less frequently reported, or atypical descriptions were given. Educational efforts are needed to improve recognition of atypical stroke symptoms by stroke victims and EMS professionals.

Acute Disease↗

Electrocerebral silence with preserved but reduced cortical brain perfusion.

Isoelectric electroencephalogram in conformance with clinical findings is strongly suggestive of brain death. In clinical practice, isoelectric electroencephalogram in not-brain-dead patients is rarely seen. We report on a 53-year-old patient who suffered ischaemic encephalopathy after cardiopulmonary arrest. He had residual brainstem function with sufficient spontaneous breathing and evidence of cerebral blood flow on single photon emission computed tomography scan, but his electroencephalogram was isoelectric. He survived this condition for more than 7 weeks. This case demonstrates that isoelectric electroencephalogram can not be equated with brain death, and that in prognostic assessment both clinical findings and supportive technical methods are mandatory.

Brain↗

Delayed cerebrovascular autoregulatory response to ergometer exercise in normotensive elderly humans.

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

Adult↗

Burden of care in amyotrophic lateral sclerosis.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal disease with unique demands on patients and carers. PATIENTS AND METHODS: The total burden of care and burden components in 37 ALS carers were measured using validated questionnaires. Furthermore, influencing factors (functional impairment of the patient, additional carers, participation in support groups) were assessed. RESULTS: The mean total burden of care for ALS was low compared with dementia, mixed neuropsychiatric and internal diseases, but was correlated with functional impairment (P = 0.003). The main burden components were 'personal and social restrictions' and 'physical and emotional problems'. Problem behaviour of the patients was low in general, but was higher in carers participating in support groups (P = 0.002). Carers supported by additional carers had higher strain. CONCLUSION: The low burden of ALS carers may be caused by the low incidence of problem behaviour in ALS patients. However, if problem behaviour exists, carers participate more often in support groups, indicating the need for assistance. The burden of care increases with the functional impairment. Support for the carers has to start sooner.

Adult↗

Post-apoplectic reorganization of cortical areas processing passive movement and tactile stimulation--a neuromagnetic case study.

Magnetoencephalography (MEG) was used in a patient with right centro-parietal stroke to investigate the cortical processing of tactile pneumatic stimulation and passive movement of the impaired left and unaffected right-hand index finger. Source localization of somatosensory evoked magnetic fields (SEF) recorded 2 weeks after infarction demonstrated a spatial displacement of the contralateral SI generators in the affected hemisphere. The distance between SI sources activated by either stimulation technique was noticeably enlarged in comparison to the left hemisphere and to previous data from 12 healthy subjects. Follow-up MEG after 6 months revealed a closer spatial arrangement of the two modality-specific SEF generators and a diminution of the interhemispheric asymmetry of proprioception-related SI sources. The topographical alterations were accompanied by clear clinical improvement of both joint position sense and tactile sensation. The occurrence of ipsilateral SI activity following passive movement of only the impaired index finger might suggest a disinhibition of subthreshold, transcallosal excitatory pathways.

Brain Ischemia↗

Reversible prolongation of motor conduction time after transcranial magnetic brain stimulation after neurogenic claudication in spinal stenosis.

STUDY DESIGN: A consecutive and controlled cohort study. OBJECTIVES: To assess the value of motor conduction time (MCT) between cortex and symptomatic leg muscles after transcranial magnetic brain stimulation as an indicator of reversible root ischemia in patients with neurogenic claudication in spinal stenosis. SUMMARY OF BACKGROUND DATA: Neurogenic claudication in spinal stenosis is thought to result from transient ischemia of active nerve root fibers. Subgroups of these patients have slowing of sensory or motor nerve root conduction during spinal claudication. MATERIAL AND METHODS: Forty-two patients with spinal claudication and radiologically confirmed signs of spinal stenosis were consecutively recruited. Motor conduction time was measured before and repetitively after challenge of walking on a treadmill (four stimuli per minute) until disappearance of the symptoms. Data of 30 patients (65 +/- 10 years) with a defined onset of motor-evoked potentials were compared with those of 12 control subjects (62 +/- 12 years). RESULTS: One minute after treadmill challenge, MCT increased in all 13 patients with signs of an exercise-dependent neurologic deficit by at least 1 msec (mean increase, 1.6 +/- 0.6 msec; < 0.001). Test-retest comparisons in six of these patients revealed good reproducibility of the MCT increase (coefficient of repeatability, 1.24 msec). In contrast, MCTs were unchanged or decreased in all 17 patients without exercise-dependent neurologic deficit ( < 0.01) and in the control subjects ( < 0.05). CONCLUSIONS: Measurements of MCT before and after treadmill challenge can demonstrate reversible root ischemia in patients with spinal claudication and exercise-dependent deficit of thickly myelinated nerve root fibers.

Aged↗

Somatotopic organization of the ventral and dorsal finger surface representations in human primary sensory cortex evaluated by magnetoencephalography.

Cortical reorganization of the subtly differentiated hand map after peripheral nerve injury might be better understood if there was a topographic conception of the homuncular representation of the dorsal finger surfaces in humans, in addition to the well-established sequential rostrocaudal array of the ventral finger aspects in cortical area 3b. In the present magnetoencephalographic study, tactile pneumatic stimulation was delivered to the fingertip and to the ventral and dorsal proximal phalanx of each digit of the dominant hand in 20 right-handed volunteers. Source localization of equivalent current dipoles underlying the recorded somatosensory evoked magnetic field was performed using a Cartesian coordinate system established by the anatomical landmarks nasion and preauricular points. Of the first major peak of each somatosensory evoked field, the region with the maximum field power (root-mean-square across channels) was selected for source reconstruction. Analysis of variance for repeated measures yielded significant results with respect to the arrangement of digits along the vertical coordinate axis, demonstrating a sequential array from the most inferiorly located D1 to the most superiorly located D5 for all different stimulus positions. This is the first study providing evidence for a sequential topographical arrangement of not only the ventral but also the dorsal surface representations of the individual digits in the human somatosensory cortex. The study contributes to a better understanding of the somatosensory hand representation in human primary cortex and provides useful information with regard to cortical plasticity studies in patients with peripheral nerve injuries at the upper extremity.

Adult↗

Temporo-spatial analysis of cortical activation by phasic innocuous and noxious cold stimuli--a magnetoencephalographic study.

Clinical findings and recent non-invasive functional imaging studies pinpoint the insular cortex as the crucial brain area involved in cold sensation. By contrast, the role of primary (SI) and secondary (SII) somatosensory cortices in central processing of cold is controversial. So far, temporal activation patterns of cortical areas involved in cold processing have not been examined. Using magnetoencephalography, we studied, in seven healthy subjects, the temporo-spatial dynamics of brain processes evoked by innocuous and noxious cold stimulation as compared to tactile stimuli. For this purpose, a newly designed and magnetically silent cold-stimulator was employed. In separate runs, cold and painful cold stimuli were delivered to the dorsum of the right hand. Tactile afferents were stimulated by pneumatic tactile stimulation.Following innocuous cold stimulation (DeltaT=5+/-0.3 degrees C in 50+/-2ms), magnetic source imaging revealed an exclusive activation of the contra- and ipsilateral posterior insular cortex. The mean peak latencies were 194.3+/-38.1 and 241.0+/-31.7ms for the response in the ipsi- and contralateral insular cortex, respectively. Based on the measurement of onset latencies, the estimated conduction velocity of peripheral nerve fibres mediating cold fell in the range of Adelta-fibres (7.4+/-0.8 m/s). Noxious cold stimulation (DeltaT=35+/-5 degrees C in 70+/-12ms) initially activated the contra- and ipsilateral insular cortices in the same latency ranges as innocuous cold stimuli. Additionally, we found an activation of the contra- and ipsilateral SII areas (peak latencies 304+/-22.7 and 310.1+/-19.4ms, respectively) and a variable activation of the cingulate cortex. Notably, neither cold- nor painful cold stimulation produced an activation of SI. By contrast, the evoked cortical responses following tactile stimulation could be located to the contralateral SI cortex and bilateral SII. In conclusion, this study strongly corroborates the posterior insular cortex as the primary somatosensory area for cortical processing of cold sensation. Furthermore, it supports the role of SII and the cingulate cortex in mediating freeze-pain. Therefore, these results suggest different processing of cold, freeze-pain and touch in the human brain.

Adult↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Baroreflex stimulation shows impaired cardiovagal and preserved vasomotor function in early-stage amyotrophic lateral sclerosis.

OBJECT: In ALS patients, autonomic nervous system dysfunction might account for an additional reduction of the quality and expectancy of life of individual patients and contribute to unexpected early fatalities. This study was undertaken to assess baroreflex-mediated vagal and sympathetic cardiovascular control of the heart and blood vessels in ALS patients. METHODS: In 12 early-stage ALS patients (age 54 +/- 4 years) and 12 controls (age 55 +/- 3 years) we assessed resting baroreflex sensitivity (BRS) by spectral analysis, then stimulated the carotid baroreflex by oscillating neck suction at 0.1 Hz to assess the autonomic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. RESULTS: Resting heart rate was significantly higher in the ALS patients than in the controls (P < 0.05), but resting baroreflex sensitivity did not differ significantly between the groups. Stimulation at 0.2 Hz induced an oscillation in R-R interval that was significantly smaller (P < 0.05) in ALS patients than in controls. R-R interval responses to 0.1 Hz stimulation were significantly (P < 0.01) reduced in ALS patients compared to controls. Responses of blood vessels to 0.1 Hz stimulation did not differ significantly between the groups. CONCLUSION: In early-stage ALS patients, BRS might be normal at rest. Only baroreflex activation reveals impaired cardiovagal responses while sympathetic vasomotor control is preserved. Treatment to restore sympathetic-parasympathetic balance to the heart could prevent early cardiovascular fatalities in some ALS patients.

Amyotrophic Lateral Sclerosis↗