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Biomedical subjects

C H Lücking

Publications and source records attributed to C H Lücking.

At least 37 records · Page 2Linked to original sources

Cortical current density reconstruction of interictal epileptiform activity in temporal lobe epilepsy.

OBJECTIVE: To investigate the value of cortical current density (CCD) reconstruction in localizing intracranial generators of interictal epileptiform activity in mesial and lateral temporal lobe epilepsy (TLE). METHODS: Non-linear minimum L(1)-norm CCD reconstruction (with current sources restricted to the individual cortical surface and a realistic boundary element method (BEM) head model) was used to localize and to study the propagation of interictal epileptiform EEG activity in 13 pre-surgical patients with TLE. RESULTS: In all but one patient with mesial temporal lesions, an initial activation maximum corresponding to the ascending part of averaged sharp waves was found in the ipsilateral anterior basolateral temporal lobe, mostly extending up to the affected mesial structures whose resection rendered the patients seizure-free. In all 3 patients with lateral temporal lesions, the activation was initially confined to temporal neocortex immediately adjacent to the epileptogenic lesion. Towards the peak of sharp waves, two patients showed a propagation of interictal activity to anterior and posterior and partly contralateral temporal regions. A conventional EEG analysis based on amplitude maxima or phase reversal would have missed the initial onset zone. CONCLUSIONS: The findings demonstrate that CCD reconstruction can be a valuable additional non-invasive component in the multimodal pre-surgical evaluation of epilepsy patients.

Adolescent↗

Tuberculous meningoencephalitis in HIV-seronegative patients: variety of clinical presentation and impact on diagnostics and treatment.

UNLABELLED: Tuberculous meningoencephalitis (TBM), an infrequent disease in Western European countries, shows a wide heterogeneity of clinical symptoms. MATERIAL AND METHODS: We present 4 patients (age range 42-72 years) with the definite diagnosis of isolated TBM. All patients were HIV-seronegative, only 1 patient was known to be immunoincompetent on admission due to acute myelocytic leukemia; other reasons for immune suppression were detected in 2 other patients (leukemia and idiopathic CD4+ T-lymphocytopenia, respectively). RESULTS: The diagnosis of TBM was confirmed in 3 cases by culture from CSF, in 1 case Mycobacterium tuberculosis was proven only in tracheal aspirate. In 1 patient M. bovis was found, which is an extremely rare cause of TBM in Germany. We report the contributions of different diagnostic tools (CSF analysis, neuroimaging) in reaching the presumptive diagnosis and in monitoring the further course. All patients developed neurological complications despite prompt tuberculostatic treatment. Three of the patients presented a chronic severe loss of consciousness of unclear origin. CONCLUSION: The possible causative relationships of these complications and their impact on the prognosis are discussed.

Adult↗

Evaluation of impaired dynamic cerebral autoregulation by the Mueller manoeuvre.

Arterial blood pressure (ABP) shows polyphasic changes during the Mueller manoeuvre (voluntary negative intrathoracic pressure). The aim of the present study was to investigate (1) whether these changes could be applied to detect impaired dynamic cerebral autoregulation (dCA) in carotid stenosis and (2) whether the degree of indicated impairment correlates with transfer function phase as another current measure for dCA (deep breathing method) and CO2-reactivity. We examined 13 patients with severe unilateral carotid artery stenosis and 16 age-matched controls during 15-s Mueller manoeuvres (MM) at -30 mmHg using bilateral transcranial Doppler sonography and non-invasive ABP recordings (Finapres, 2300, Ohmeda, Englewood, CO, USA). After an initial biphasic oscillation, cerebral blood flow velocity (CBFV) and ABP decreased to below baseline. CBFV reincreased in controls and on contralateral sides in patients 6.0 s (3.8-9.5 s, median and range) after the onset of the decrease, despite a further fall in ABP. CBFV over the affected side revealed a significantly delayed reincrease (8.0 (5.6-10.3) s; P<0.01) combined with a relatively flat and inertial amplitude behaviour. An applied autoregulation index derived from the MM (mROR), phase shift and CO2-reactivity were severely reduced on the affected side in patients (P<0.01). Reduction of the mROR correlated significantly with reduction of phase shift (r=0.69; P=0.002) and CO2-reactivity (r=0.78; P=0.002). In conclusion, the different cerebral haemodynamic pattern during the MM in patients is likely to reflect impaired dCA. The degree of indicated impairment correlates with that of transfer function phase and CO2-reactivity. Therefore, the MM represents a convenient method for grading of compromised cerebral haemodynamics in patients with carotid artery stenosis.

Adult↗

Adaptive changes of saccadic eye-head coordination resulting from altered head posture in torticollis spasmodicus.

We asked whether and how the abnormal head posture in torticollis patients affects saccadic gaze shifts and impairs the associated head movements. We wanted to learn to what extent observed changes directly result from the disease or reflect compensatory mechanisms, secondary to the altered head posture. We compared the results of patients with those of normal subjects. When patients viewed a centric target, their heads were a priori deviated in the direction of the torticollis, with orbital eye position showing a compensatory offset in the opposite direction. These abnormal eye and head positions were re-established when patients returned from an eccentric gaze position by means of a centripetal gaze shift, independently of its direction and magnitude, unlike in normal subjects who always recentred eyes and head. In normal subjects the share of the head in the total gaze shift amounted to about 70%, whereas in patients it contributed only 30%, necessitating correspondingly larger orbital eye displacements and eccentricities. Moreover, patients' head movements were asymmetric; they were larger when gaze was shifted into, or returned from the hemifield contralateral to the torticollis direction compared with gaze shifts in the ipsilateral hemifield. The eyes displayed a reversed asymmetry. Patients showed a significant increase in gaze latency and head versus eye delay as well as in the number of corrective saccades. However, head velocity was normal in four out of seven patients. Moreover, all patients made normal eye saccades (peak velocity, duration, gaze error), except for the increase in latency, which also occurred when gaze was shifted without head movements. Thus, patients' saccadic eye-head coordination showed abnormalities which mainly concerned the involved head movements. We suggest that the observed changes do not reflect a direct involvement of the disease upon the gaze shift mechanism, but can be interpreted as adaptive changes that compensate for the altered head posture. We formalized this view in the form of a dynamic model.

Adaptation, Physiological↗

Effect of bilateral subthalamic nucleus stimulation on gait in Parkinson's disease.

The fundamental disturbance of the parkinsonian gait is the reduction in walking velocity. This is mainly due to reduction in stride length, while cadence (steps/min) is slightly enhanced. Treatment with L-dopa increases stride length while cadence is unchanged. Chronic stimulation of the thalamus has no effect on Parkinsonian gait. The efficacy of electrical stimulation of the subthalamic nucleus (STN) on gait in advanced Parkinson's disease has been clearly demonstrated clinically. The aim of the present study was to quantify the changes in gait measures induced by STN stimulation and L-dopa and to assess possible differential or additive effects. Eight Parkinson's disease patients (mean +/- SD age 48.1 +/- 7.3 years) with chronic bilateral STN stimulation (mean duration of disease 13.3 +/- 2.4 years, mean stimulation time 15.4 +/- 10.6 months) and 12 age-matched controls were investigated. Subjects walked on a special treadmill with a closed-loop ultrasound control system that used the subject's position to adjust treadmill speed continuously for the actual walking velocity. In an appropriate crossover design, spatiotemporal gait measures and leg joint angle movements were assessed for at least 120 stride cycles in four treatment conditions: with and without stimulation and with and without a suprathreshold dose of L-dopa. With STN stimulation, there were increases of almost threefold in mean walking velocity (from 0.35 to 0.96 m/s) and stride length (from 0.34 to 0.99 m). Cadence remained constant. The range of motion of the major leg joints also increased. L-Dopa alone had a slightly weaker effect, with an increase in walking velocity to 0.94 m/s and in stride length to 0.92 m at a similar cadence. These increased values were in the range of those for healthy age-matched subjects performing the same task. The combination of both treatments further increased the mean walking velocity to 1.19 m/s and stride length to 1.20 m at an unchanged cadence. However, not all patients receiving STN stimulation improved further when they also received L-dopa. These results demonstrate that chronic bilateral STN stimulation, like treatment with L-dopa, improves walking velocity by increasing stride length without changing cadence. STN stimulation almost exclusively affects mechanisms involved in the control of spatial gait measures rather than rhythmicity. The gait measures obtained with STN stimulation alone are in the range of control subjects.

Adult↗

Limbic encephalitis investigated by 18FDG-PET and 3D MRI.

Two patients with clinically probable or possible limbic encephalitis (LE) are reported, both cases with typical findings in clinical symptoms (severe neuropsychological deficits and complex partial seizures) and in routine magnetic resonance imaging (MRI) (hyperintense mesiotemporal lesions). Underlying malignancy was identified (rectal carcinoma) in one case but could not be detected in the other patient. The 2 patients were investigated by cerebral 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) and 3-dimensional (3D) MRI, and abnormalities in metabolic activity were mapped using coregistration of spatially normalized PET and MRI. Highly significant focal hypermetabolism in bilateral hippocampal areas was found in both cases. The authors' findings support FDG-PET coregistered to 3D MRI as a potentially valuable additional tool in the imaging diagnostics of LE. Results are discussed with respect to the clinical symptoms and previously reported imaging findings in the disease.

Brain↗

Dynamic cerebral autoregulation testing as a diagnostic tool in patients with carotid artery stenosis.

Evaluation of dynamic cerebral autoregulation might yield a physiologically more adequate measure of cerebral hemodynamic impairment in carotid artery stenosis than CO2-reactivity. This study re-evaluates and compares the Valsalva maneuver (VM) and phase shift during deep breathing. Nineteen patients with severe carotid artery stenosis and 17 age-matched controls were examined using transcranial Doppler sonography and non-invasive blood pressure recordings (Finapres). Phase shift was determined by cross-spectral analysis, responses to VM were graded by the formerly-introduced autoregulation slope index (ASI) and the new Valsalva time index (VTI). Phase shift and autoregulatory indices were significantly reduced on the affected side (p < 0.001). Correlations with CO2-reactivity were significant when pooling values of controls and patients (r from 0.54 to 0.78; p < 0.001). Correlations except for the VTI (r = -0.65; p = 0.002) were not significant considering only the affected side in patients. Correlations of pooled values between phase shift and VM-derived indices were significant (VTI r = -0.62; p < 0.001; ASI r = 0.49; p < 0.001), within patients only when comparing side-to-side differences (VTI r = -0.58; p = 0.009; ASI r = 0.52; p = 0.023). In conclusion, detection of impaired cerebral autoregulation is possible both by deep breathing and VM. The new VTI seems to be more suitable than the conventional ASI. Inter-method agreement concerning the extent of impairment is only acceptable for intra-individual side-to-side differences. Since absolute values of one autoregulation testing method or CO2-reactivity alone might fail, various tests should be combined for comprehensive assessment of cerebral hemodynamic impairment.

Carbon Dioxide↗

Lateralization of movement-related potentials and the size of corpus callosum.

Using structural MRI and whole-head EEG recordings, we analyzed the correlations between the anatomical parameters of the corpus callosum and the hemispheric distribution of the cortical movement-related potentials during right finger and shoulder movements in nine right-handed men. Statistically significant correlation was found only in finger movements. A relatively large genu and the anterior part of the truncus of the corpus callosum correlated with enhanced pre-movement EEG potential over the ipsilateral M1/S1 area. The lateralization of the movement-related potentials correlates with the size of those callosal regions which connect the homologous areas of the primary sensorimotor and frontal cortices.

Adult↗

Gabapentin-lactam (8-aza-spiro[5,4]decan-9-on; GBP-L) inhibits oxygen glucose deprivation-induced [3H]glutmate release and is a neuroprotective agent in amodel of acute retinal ischemia.

The modulation of the enhanced release of [3H]glutamate following ischemia-like conditions was studied in rat hippocampal slices using a superfusion system. Ischemia was simulated by a glucose-free medium equilibrated with 95% N2 and 5% CO2. In this model the potential neuroprotective effects of several substances on [3H]glutamate release induced by ischemia-like conditions were investigated. Gabapentin-lactam (8-aza-spiro-5,4-decan-9-on; GBP-L) was synthesised and patented in our laboratory. GBP-L (100 microM) reduced the oxygen glucose deprivation-induced [3H]glutamate release by 42.5%, CI95=[33.4%, 51.5%]. The KATP channel antagonist glibenclamide (1 microM) blocked this effect completely. The high antagonist potency was reflected by an apparent pA2-value of glibenclamide of 8.3, CI95=[6.8, 9.4]. Minoxidil sulfate (10 microM), a KATP channel opener, mimicked the effect of GBP-L (inhibition by 22.8%, CI95=[13.2%, 32.5%]). Similarly to its lactam, also gabapentin (100 microM) reduced the oxygen glucose deprivation-induced [3H]glutamate release by 30.6%, CI95=[15.5%, 45.7%], whereas the "antiglutamatergic" drug riluzole was ineffective. GBP-L and gabapentin were also tested in an in vivo model of acute retinal ischemia in rats. The intraocular pressure was elevated for 1 h above the systolic blood pressure. In the control group, 17.5%, CI95=[13%, 22%], of retinal ganglion cells had survived after 2 weeks. GBP-L doubled the number of surviving ganglion cells up to 35%, CI95=[27%, 43%], while gabapentin had no effect. This difference between gabapentin and its lactam may be due to different pharmacokinetic properties: In contrast to the gamma-amino acid gabapentin, GBP-L is uncharged and therefore might diffuse more easily through biological membranes, e.g. the plasma membrane, to get access to an intracellular locus of action. Thus, the neuroprotective properties in vivo and the diminished oxygen glucose deprivation-induced [3H]glutamate efflux in vitro of the presumed KATP channel agonist GBP-L suggest that this substance might be therapeutically applied in pathological situations induced by a rise in extracellular glutamate and/or neuronal cell death.

Algorithms↗

Tremor-correlated cortical activity detected by electroencephalography.

OBJECTIVE: In this study we investigated whether cortical activity related to Parkinsonian resting tremor can be detected by electroencephalography (EEG). METHODS: Seven patients with idiopathic Parkinson's disease suffering from unilateral tremor participated in the study. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles as well as a high resolution EEG were recorded simultaneously. Coherencies between EEG and EMG were calculated. RESULTS: In all patients, we found highly significant coherencies at the tremor frequency or its first harmonic between the tremor EMG and contralateral EEG channels. There were no significant coherencies between the tremor EMG and ipsilateral EEG channels. Isocoherency maps illustrating the topography of the coherencies over the scalp showed that the maximum coherencies were situated over the cortical motor areas. In one case, a high coherency was also found over the parietal cortex. CONCLUSIONS: The results show for the first time that tremor-correlated cortical activity can be detected by electroencephalography. The findings underline that motor areas of the cerebral cortex are involved in the neuronal network generating resting tremor in Parkinson's disease.

Aged↗

Visual contrast response functions in Parkinson's disease: evidence from electroretinograms, visually evoked potentials and psychophysics.

OBJECTIVES: Visual contrast detection thresholds and suprathreshold contrast discrimination thresholds were compared to luminance and flash/pattern electroretinograms (ERG) and visually evoked potentials (VEP) in patients with Parkinson's disease (n = 31), patients with multiple system atrophy (n = 6), patients with progressive supranuclear palsy (n = 6) and control patients without central nervous disease (n = 33). METHODS: The stimuli were luminance modulated full-field (flash) or horizontally oriented sinewave gratings (pattern), the latter having either a low (0.5 cycles/deg) or medium (4.0 cycles/deg) spatial frequency. Stimulus contrast ranged from 10 to 80% so that contrast response functions could be derived. RESULTS: Contrast thresholds were higher in the patients with Parkinson's disease than in the control patients. Contrast discrimination thresholds were also somewhat elevated in patients with Parkinson's disease. Pattern ERG amplitudes were significantly reduced in patients with Parkinson's disease for the medium spatial frequency stimulus, but less for the low spatial frequency and flash stimuli. CONCLUSIONS: Our results suggest that Parkinson's disease impairs contrast processing in the retina. VEP amplitudes did not significantly differ between the groups for the conditions tested. Patients with progressive supranuclear palsy also showed impaired contrast perception and reduced ERG amplitudes, whereas patients with multiple system atrophy were less impaired.

Aged↗

Oscillatory cortical activity and movement-related potentials in proximal and distal movements.

OBJECTIVES: Event-related desynchronization (ERD) of alpha- and beta-rhythms, the post-movement beta-synchronization and the cortical movement-related potentials were analyzed in distal (finger) and proximal (shoulder) movements. METHODS: EEG was recorded in 7 healthy right-handed men using a 59-channel whole-head EEG system while subjects performed self-paced movements. RESULTS: The amplitude of the Bereitschaftspotential (BP) was greater over the central midline area and smaller over the contralateral sensorimotor hand area in shoulder than in finger movements. The maximal alpha- and beta-ERD was localized at parietal electrodes in shoulder movements and over the left and right sensorimotor hand area in finger movements. The post-movement beta-ERS was greater in shoulder than in finger movements, especially at the electrode located 3.5 cm left of the central midline electrode. A significant correlation between the slope of the terminal portion of the BP (negative slope) and amplitude of the post-movement beta-synchronization was observed in shoulder but not in finger movements. CONCLUSIONS: Enhancement of BP over the central midline electrode suggests increased activation of the supplementary motor area in proximal movements. The spatial distribution of the alpha- and beta-ERD and of the post-movement beta-ERS shows topographic differences which may refer to the somatotopic organization of the primary sensorimotor cortex with shoulder representation medial to hand and fingers. The correlation between the negative slope and the post-movement beta-ERS in proximal movements supports the view that the brief post-movement inhibition over the motor cortical area is related to the pre-movement activation of that area.

Adult↗

Development of the corticospinal system and hand motor function: central conduction times and motor performance tests.

Maturation of the corticospinal (CS) tract and hand motor function provide paradigms for central nervous system development. In this study, involving 112 participants (aged from 0.2 to 30 years), we evaluated central motor conduction times (CMCT) obtained with transcranial magnetic stimulation (TMS) during preinnervation conditions of facilitation and relaxation. Auditory reaction time, velocity of a ballistic movement of the arm, finger tapping, diadochokinesis, and fine motor visuomanual tracking were also examined. The maturation profiles for every parameter were calculated. CMCTs for the different preinnervation conditions reached adult values at different times and this could be explained by maturation of excitability at the cortical and spinal level. A stable phase for CMCTs and reaction time was reached during childhood. Parameters which measured motor speed and skill indicated that the development of these continued into adulthood. The maturation of the fast CS tract seems to be completed before the acquisition of the related motor performance has been accomplished. In conclusion, we could demonstrate that data from several neurophysiological methods can be combined and used to study the maturation of the function of the nervous system. This approach could allow appraisal of pathological conditions that show parallels with omissions or lack of developmental progress.

Adolescent↗

Cerebral haemodynamics during the Mueller manoeuvre in humans.

Voluntary negative intra-thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at -30 mmHg intra-thoracic pressure, 27 young (aged 21-31 years, group A) and 11 older (52-64 years, group B) healthy adults were studied using transcranial Doppler and non-invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4.7 s (2.4-8.5) (median and range) and in group B 5.7 s (4. 1-7.2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure-flow relationship (DPFR), indicated a reduction of intra-cranial pressure during the first half of the strain. DPFR-related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1.5 s before the observed CBFV increase. A modification of the previously described dynamic auto-regulation index ROR correlated significantly with CO2 reactivity values (r=0.61, P=0.001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto-regulation and may provide an estimate of dynamic cerebral auto-regulation capacity. In older adults, the maximal dynamic auto-regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.

Adult↗

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↗

Classical conditioning of the electrically elicited blink reflex in humans: a new method of data analysis.

The eyeblink conditioning paradigm is a well-established model to study learning processes in humans and animals. Especially results from animal studies have supplied new insight into physiological pathways and brain structures involved in associative motor learning and memory. An important role of the cerebellum and its afferent fiber systems could be shown. Recent studies in humans have given evidence that results of animal experiments can be applied directly to the human condition. A high variation of baseline EMG activity and/or spontaneous blinks may influence the analysis of classical conditioning of the electrically elicited blink reflex in humans. To optimize differentiation between real conditioned responses and stimulus-independent EMG activity, we developed an algorithm which is fully automated and independent of a possible bias of an examiner. In a first step the algorithm decides whether a subject fulfills the criteria of a successful learning process or not. The second step quantifies the learning process. For quantification of the learning process, the following parameters were calculated: number of conditioned responses, onset of conditioning, time and amount of maximal conditioning, speed of conditioning and speed of habituation. According to our criteria, 80% of the healthy volunteers acquired conditioned responses. There is an age-related decline in eyeblink classical conditioning. Analysis of patient groups with different types of lesions will further improve our knowledge and understanding of pathways involved in learning processes in humans. The proposed new algorithm of data analysis takes less than 10 s on a standard computer, is more sensitive and more specific in detecting conditioned responses and, therefore, may further improve the value and reliability of the eyeblink conditioning paradigm in clinical research.

Adult↗