[Different manifestations of the cerebral nocardiosis]. / Unterschiedliche Manifestationsformen der zerebralen Nokardiose.

Nocardial infections affect mainly the respiratory tract but also can attack the CNS. Clinical experience with cerebral nocardiosis is very limited. We present two patients with very different cerebral affections due to nocardiosis. Cerebral nocardial infections can cause both multiple small abscesses and single large abscesses in the human brain. Despite the rare incidence of cerebral nocardiosis, it is an important differential diagnosis of expansive processes and abscesses in the CNS.

Short-term modulation of the ipsilateral primary sensory cortex by nociceptive interference revealed by SEPs.

We studied the modulation of the topographic arrangement of the human ipsilateral primary somatosensory cortex following interference of nociceptive stimuli by means of dipole source analysis. Multichannel somatosensory evoked potentials were obtained by electrical stimulation of digits 1 and 5 of the left hand before, during and after the application of pain to digits 2-4 of the right hand. The primary cortical response of the SEP (N20) was obtained for dipole localization of the representation of the primary sensory cortex receiving input from digits 1 to 5. The 3D-distance between these sides was calculated for further analysis. To account for possible attentional effects recordings were performed while simultaneously to this intervention subjects were asked to turn their attention to the right or left hand in a pseudorandom order. The application of pain induced an expansion of the 3D-distance between digits 1 and 5. Focusing attention to the stimulated limb or the site of the intervention did not yield to an additional effect. Our results provide further evidence for the presence of a quickly adapting interaction between primary somatosensory areas of both hemispheres following an interference of nociceptive stimulation in SEPs. This modifying process is probably mediated by interhemispheric and intercortical connections leading to hyperexcitability of the primary sensory cortex contralateral to that receiving nociceptive input. Spatial attention does not seem to have an impact on this kind of short-term intercortical plasticity.

Interference of tactile and pain stimuli on thalamocortical signal processing in humans revealed by median nerve SEPs.

OBJECTIVE: We investigated the interference of tactile and painful stimuli on human early somatosensory evoked potentials (SEPs) including high frequency oscillations (HFOs) to further study thalamocortical processing of somatosensory information. METHODS: Multi-channel median nerve SEPs were recorded during (1) no interference, (2) sensory interference by tactile stimulation to digits 2 and 3, and (3) application of pain to the same digits. Spatio-temporal source analysis separated brain stem (S1), thalamic (S2) and two cortical sources (S3, S4), which were evaluated for the low (20-450 Hz) and high (450-750 Hz) frequency portion of the signal. RESULTS: Low frequency SEPs showed a decrease of activity at cortical source S3 during both conditions, while thalamic source S2 was significantly increased during pain interference. HFOs showed an increase of cortical source S3 and in trend of thalamic source S2 and cortical source S4 during both kinds of interference. CONCLUSIONS: Although the painful stimulus might not be specific for the nociceptive afferents, the present data affirm that at this early stage of sensory information processing within the primary sensory cortex (area 3b, area 1) pain is handled similar to sensory interference. SIGNIFICANCE: HFOs might represent an intrinsic "somatosensory alerting" system which reacts to both interference stimuli in a similar way, therefore indicating an interference without a qualitative evaluation.

[Hypokalemic paralysis with thyrotoxicosis]. / Hypokaliämische Lähmung bei Hyperthyreose.

Hypokalemic periodic paralysis as a complication of thyrotoxicosis (thyrotoxic periodic paralysis) most often occurs in east Asian men. It is characterised by recurrent episodes of flaccid paralysis, hypokalemia, and underlying hyperthyroidism. It needs to be distinguished from sporadic and familial forms of periodic hypokalemic paralysis. No disturbances in the acid-base state and no extracorporal potassium loss are present. We report on the typical case of a young Chinese man presenting with hypokalemic periodic paralysis associated with yet unknown Graves' disease. Intravenous substitution of potassium and oral propranolol were administered. Complete remission was achieved after 10 hours. After medical therapy had normalised thyroid hormone levels, no further hypokalemic paralytic attacks occurred.

Different origins of low- and high-frequency components (600 Hz) of human somatosensory evoked potentials.

OBJECTIVE: Human median nerve somatosensory evoked potentials (SEPs) contain a low-amplitude (<500 nV) high-frequency (approximately 600 Hz) burst of repetitive wavelets (HFOs) which are superimposed onto the primary cortical response 'N20.' This study aimed to further clarify the cortical and subcortical structures involved in the generation of the HFOs. METHODS: 128-Channel recordings were obtained to right median nerve stimulation of 10 right-handed healthy human subjects and in 7 of them additional to right ulnar nerve. Data were evaluated by applying principal component analysis and dipole source analysis. RESULTS: Different source evaluation strategies provided converging evidence for a cortical HFO origin, with two different almost orthogonally oriented generators being active in parallel, but with a phase shift of a quarter of their oscillatory period, while the low-frequency 'N20' is adequately modeled by one tangential dipole source. Median and ulnar derived low-frequency and HFO cortical sources show a somatotopic order. Additionally, generation of the HFOs was localized in subcortical, near-thalamic and subthalamic source sites. The near-thalamic dipole was located at significantly different sites in HFO and low-frequency data. CONCLUSIONS: The cortical HFO source constellation points to a 'precortical' source in terminals of thalamocortical fibers and a second intracortical HFO origin. Furthermore, HFOs are also generated at subcortical and even subthalamic sites. Near-thalamic, the HFO and low-frequency signals are generated or modulated by different neuron populations involved in the thalamocortical outflow.

Activation of the human posterior parietal and temporoparietal cortices during audiotactile interaction.

We recorded cortical-evoked responses with a whole-scalp neuromagnetometer to study human brain dynamics associated with audiotactile interaction. The subjects received unilateral auditory (A) or tactile (T) stimuli, or both stimuli simultaneously (AT), alternating to the left and right side. Responses to AT stimuli differed significantly from the algebraic sum of responses to A and T stimuli (A + T) at 75-85 and 105-130 ms and indicated suppressive audiotactile interaction. Source modeling revealed that the earlier interaction occurred in the contralateral posterior parietal cortex and the later interaction in the contralateral parietal opercula between the SII cortex and the auditory cortex. The interaction was significantly stronger in the left than the right hemisphere. In most subjects, AT responses were far more similar to T than to A responses, suggesting suppression of auditory processing during the spatially and temporally concordant audiotactile stimuli in which the tactile component was subjectively more salient.

Immediate cortical reorganization after local anesthetic block of the thumb: source localization of somatosensory evoked potentials in human subjects.

Psychophysical observations after anesthesia of the thumb raise the question whether the functional border between the thumb and the index is functionally distinct. We present a source localization study using equivalent current dipole modeling of somatosensory evoked potentials (SEPs) following mechanical air-puff stimulation of the first, second and third digits before and during anesthesia of the thumb. Source reconstruction was based on 96-channel SEP recordings. During anesthesia of the thumb the distance between the cortical representation of the thumb and the second and third digits immediately decreased. This indicates a shift of the cortical representation of the second and third digits towards the deafferented area of the anesthetized thumb. Thus, the present results did not confirm the hypothesis of a functional border of the cortical representation between thumb and index finger in this particular task.

Spatiotemporal imaging of electrical activity related to attention to somatosensory stimulation.

The aim of the present study was to localize the effects of spatial attention on somatosensory stimulation in EEG. Median and tibial nerve were stimulated at all four limbs in a random order. Subjects were instructed to count the events on either the right median or the right tibial nerve. Attention-induced changes in the somatosensory evoked potentials (SEP) were revealed by subtracting the median nerve SEPs recorded while subjects attended to stimuli applied to the tibial nerve from those obtained during attention to the stimulated hand. In a current density reconstruction approach source maxima in the time range from 30 to 260 ms after median nerve stimulation were localized and the time courses of activation were elaborated by dipole modeling. Six regions were identified which contribute significant source activity related to selective spatial attention: contralateral postcentral gyrus (Brodman area (BA) 3), contralateral mesial frontal gyrus (BA 6), right posterior parietal cortex (BA 7), anterior cingulate gyrus (BA 32), and bilateral middle temporal gyrus (BA 21). Activation started at the right posterior parietal cortex, followed by the contralateral middle temporal gyrus, probably representing SII activity, and the middle frontal and anterior cingulate gyrus. Similar regions of source activation were revealed by tibial nerve SEP, but the effect was less pronounced and restricted almost entirely to activation of the contralateral postcentral gyrus (BA 3), anterior cingulate gyrus (BA 32), and ipsilateral middle temporal gyrus (BA 21). Our data provide evidence for a spatially separated frontal generator within the anterior cingulum, dependent on selective attention in the somatosensory modality.

Differential gating of slow postsynaptic and high-frequency spike-like components in human somatosensory evoked potentials under isometric motor interference.

Human cortical somatosensory evoked potentials (SEP) can be modified by concomitant motor tasks ('gating'), through peripheral occlusion and/or central mechanisms. The present study aimed (1) at refining earlier results concerning motor-gating of the primary cortical EPSP-related N20 response after electric median nerve stimulation, and (2) at providing first data on motor-gating of the 600 Hz SEP wavelet burst which occurs superimposed onto N20 and primarily reflects repetitive cerebral population spikes. In 12 healthy subjects median nerve SEP were elicited, using electrical stimuli with intensities below, at and above motor threshold, under either rest or an isometric fist clenching task. Amplitude and latency modifications were analysed for the peripheral compound action potential (CAP), low-frequency SEP components (N20, P25, N35 and P70) and the high-frequency burst. While the peripheral CAP remained unchanged, isometric motor innervation significantly attenuated N20, P25 and P70 amplitudes and shortened peak latencies progressively for all components after N20. In contrast, the high-frequency 600 Hz burst was modulated neither in amplitude nor in latency. Regular amplitude recruitment occurred for all components independent from the motor task, excluding channel saturation as an explanation for gating. We suggest that SEP gating under isometric motor innervation is a central process which selectively operates on specific SEP components and could partly reflect an "efference copy" mechanism.

Spatio-temporal source imaging reveals subcomponents of the human auditory mismatch negativity in the cingulum and right inferior temporal gyrus.

We investigated the generators of the mismatch negativity by means of spatio-temporal source imaging on the basis of 64-channel electroencephalography data in order to study the time course and localization of proposed frontal sources. Results indicate that there are additional generators located both within the anterior cingulate gyrus and in the right inferior temporal gyrus, clearly separated from the supratemporal generators in space and time course. The cingulate generator is activated later than the temporal ones, which supports the hypothesis of a frontally located mechanism of involuntary switching of attention triggered by the temporal change detection system. Evidence for an additional right inferior temporal generator supports the hypothesis of right hemispheric dominance in early sound discrimination.

Source reconstruction of mesial-temporal epileptiform activity: comparison of inverse techniques.

PURPOSE: To evaluate whether advanced source reconstruction such as current density reconstruction (CDR) provides additional hints for clinical presurgical evaluation, different source reconstruction techniques with idealized spherical as well as realistically shaped head models (boundary element method, BEM) were applied on interictal and ictal epileptiform activity in presurgical evaluated patients with temporal lobe epilepsy. It is discussed whether CDR and BEM give additional information for presurgical evaluation compared to "conventional" strategies, such as single moving, and spatio-temporal dipole modeling with spherical head models. METHODS: A variety of source reconstruction procedures were applied to the data of five patients with pharmacoresistent temporal lobe epilepsy with probable mesial origin: (1) single-moving dipole in a spherical head model and (2) in BEM, (3) spatio-temporal dipole modeling in a spherical head model and (4) in BEM; and (5) deconvolution with fixed locations and orientations and (6) with cortically constrained L1-norm CDR in BEM. In addition, simulated sources of temporal lobe origin were calculated in each subject with CDR to prove the basic feasibility of this technique in the particular application. RESULTS: Source activity was correctly localized within the affected temporal lobe by all source reconstruction techniques used. Neither single moving dipole, spatio-temporal modeling, nor CDR was able to localize sources at a sublobar level. In the case of two sources, single moving dipole solutions showed changes in dipole orientation in time and spatio-temporal modeling separated two sources, whereas CDR at the peak latency failed to distinguish among different origins. BEM enhanced localization accuracy. CONCLUSION: There was no advantage of using CDR. Single moving dipole as well as spatio-temporal dipole modeling in BEM leads to more precise localization within the individual anatomy and provides a simple algorithm, which is capable of indicating both the time course and the number of sources.

Sleep stage dependant changes of the high-frequency part of the somatosensory evoked potentials at the thalamus and cortex.

OBJECTIVES: It is known that the high-frequency oscillations (above 400 Hz) of the somatosensory evoked potentials (SEPs) diminish during sleep while the N20 persists (Neurology 38 (1988) 64; Electroenceph clin Neurophysiol 70 (1988) 126; Electroenceph clin Neurophysiol 100 (1996) 189). We investigated possible differential effects of sleep on the 600 Hz SEPs at the thalamus and cortex. METHODS: SEPs from 10 subjects were recorded using 64 channels following electric stimulation at the wrist during awake state and sleep stages II, IV and REM. Dipole source analysis was applied to separate brain-stem, thalamic and cortical activity in the low-frequency (20-450 Hz) and the high-frequency (450-750 Hz) part of the signal. RESULTS: The low-frequency SEPs showed a non-significant increase of the latency of the N20 and a bifid change of the waveform in 3 subjects. The high-frequency SEPs showed a significant decrease of their amplitude at the level of the thalamus and cortex but not at the brain-stem. This decrease in amplitude at the thalamus and cortex were significantly correlated. There was no effect on the latency of the signal. In addition, at the cortex, differential effects on early and late parts of the 600 Hz oscillations were found by time-frequency analysis using a wavelet transformation. CONCLUSIONS: Sleep dependent decrease of the high-frequency SEPs were first observed at the thalamus pointing to the known function of the reticular thalamic nucleus regulating arousal. The results presented here provide further evidence for a thalamic origin of the 600 Hz oscillations. In addition, on the basis of the differential effects on early (up to the N20 peak) and late (between 20 and 25 ms) parts of the signal, at least one intracortical generator of these oscillations is proposed. In general, the high-frequency SEPs (600 Hz oscillations) are supposed to reflect activity of a somatosensory arousal system.

Thalamic and cortical high-frequency (600 Hz) somatosensory-evoked potential (SEP) components are modulated by slight arousal changes in awake subjects.

Human somatosensory-evoked potentials (SEP) recorded at the scalp after conventional electrical median-nerve stimulation contain a low-amplitude (<500 nV), high-frequency (approximately 600 Hz) burst of repetitive wavelets, which are superimposed onto the primary cortical response N20. Previous electroencephalographic (EEG) studies have shown: (1) that these wavelets are generated near the hand area of the primary somatosensory cortex and in deep fibers of thalamocortical afferences; and (2) that only the 600-Hz burst, but not the N20 is decreased during sleep. Since the thalamus is involved in regulating both, selective attention and arousal, the present study aimed at characterizing the effects of focused attention and slight arousal changes on the 600-Hz oscillations. A dipole-source analysis of 64-channel SEP recordings after electric right-median-nerve stimulation allowed the comparison of brainstem, thalamic, and two cortical (one tangential, one radial) source activities in ten awake human subjects under two slightly different arousal states (eyes open vs. eyes closed), each tested for three conditions of focused attention (directed towards rare acoustic and right- or left-hand somatosensory target stimuli). While the N20 was not modified at all, the source strength of the high-frequency wavelet burst was significantly increased for eyes opened versus eyes closed, at the thalamic source site as well as for the tangentially oriented cortical source. In contrast, there were no significant differences between conditions with different attentional targets. This evidence for modulatory effects of increased arousal (eyes open) on both thalamic and cortically generated high-frequency SEP activity fits the hypothesis that the 600-Hz SEP burst at least partially represents an arousal-dependent signal generated at the thalamic level and transmitted to the primary somatosensory cortex.

[Cerebral vasculitis as a concomitant neurological illness in Crohn's disease]. / Zerebrale Vaskulitis als neurologische Begleiterkrankung bei Morbus Crohn.

In Crohn's disease, some concomitant neurological illnesses such as cerebral ischemia following arterial or venous thrombosis, subacute combined degeneration of the spinal cord following malabsorption of vitamin B12 or folic acid, opticus neuropathy, and polyneuropathy have been described. Cerebral vasculitis secondary to Crohn's disease seems to be a very rare phenomenon. We report on three such cases in three female patients (aged 26, 29, and 61 years). All patients became symptomatic with a hemiparesis; one complained additionally of a speech disorder, headache, and intermittent loss of orientation. In CT and MRI scans, multiple lesions were detected; cerebral angiography showed multiple stenoses of middle- and large-sized vessels that were compatible with cerebral vasculitis. Serologic tests concerning vasculitis were inconspicuous at that time. Under anticoagulation (in two cases) and immunosuppressive therapy, neurologic symptoms disappeared. In the following 6 to 12 months, no new neurological symptoms appeared. In two cases, Doppler sonographic controls showed stationary and, in one case, progressive intracranial stenoses. Since autoimmunologically caused inflammatory bowel diseases might be associated with vasculitis of other organs, the appearance of cerebral vasculitis secondary to Crohn's disease is a possible organ manifestation by inflamed vessels.

High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users.

Neurotoxic damage of central serotonergic systems has been demonstrated in numerous animal studies after exposure to methylenedioxyamphetamines (ecstasy). A high intensity dependence of auditory evoked potentials and, particularly, of the tangential N1/P2 source activity has been associated with low levels of serotonergic neurotransmission in humans. We performed an auditory evoked potentials study in 28 abstinent recreational ecstasy users and two equally sized groups of cannabis users and nonusers. The ecstasy users exhibited an increase of the amplitude of the tangential N1/P2 source activity with higher stimulus intensities; whereas, both control groups failed to exhibit this feature. These data are in line with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity. This feature of information processing is probably related to the well-recognized neurotoxic potential of ecstasy. Our data indicate that recreational ecstasy use may cause long-term alterations in the function (and possibly structure) of the human brain.

Differential effects of pain and spatial attention on digit representation in the human primary somatosensory cortex.

Reorganization of primary somatosensory cortex subsequent to either reduced or enhanced peripheral input is well established. Recently, plastic changes following arm amputation in humans were shown to correlate with phantom limb pain. This raised the question whether spatial attention and pain may cause cortical reorganization in the absence of deafferentation. Using non-invasive neuroelectric imaging to study the digit representation in the human primary somatosensory cortex, we report a delayed shift of the representation of digits 2-3 due to pain on the digits 4-5, which outlasted the pain by several minutes. In contrast, reorganization during spatial attention was less pronounced, was seen almost immediately and only during the condition. These data indicate that spatial attention and pain without peripheral deafferentation cause cortical reorganization by different mechanisms. The differential time course of reorganizational effects observed at the cortex may be due to modulation of the lemniscal pathways by nociceptive input from the spinal cord dorsal horn.

S-1 radiculopathy as a possible predisposing factor in focal myositis with unilateral hypertrophy of the calf muscles.

Associated with chronic S-1 radiculopathy, a 44-year-old man developed unilateral hypertrophy of the calf muscles. Electromyography revealed neurogenic alterations in the corresponding limb compatible with S-1 radiculopathy. In addition, MR-tomographic and bioptic findings were consistent with a focal inflammatory myopathy of the enlarged right gastrocnemius muscle. Predisposing factors for the localisation of a focal myositis are unknown. This case report highlights the diagnostic difficulties in distinguishing focal myositis and denervation hypertrophy following S-1 radiculopathy or secondary inflammation related to denervation. We consider the possibility that in our case the inflammatory process might have been triggered by electromyographically proven chronic denervation related to radiculopathy.

Spatial attention modulates the cortical somatosensory representation of the digits in humans.

The topographic organization of the primary somatosensory cortex adapts to alterations of afferent input. Here, electric source imaging was used to show that spatial attention modifies cortical somatosensory representations in humans. The cortical representation of the electrically stimulated digit 2 (resp. digits 2 and 3) of the right hand was more medial along the somatosensory area 3b in subjects who focused attention on digit 4 of the right hand, while it was more lateral when subjects attended digit 4 of the contralateral hand. This effect was very fast since the direction of attention was changed every 6 min. The results indicate that cortical somatosensory representations not only depend on afferent input but vary when spatial attention is directed towards different parts of the body.

N30 and the effect of explorative finger movements: a model of the contribution of the motor cortex to early somatosensory potentials.

OBJECTIVES: The source of the N30 potential in the median nerve somatosensory evoked potentials (SEP) has been previously attributed to a pre-central origin (motor cortex or the supplementary motor area, SMA) or a post-central located generator (somatosensory cortex). This attribution was made from results of lesion studies, the behavior of the potential under pathological conditions, and dipole source localization within spherical volume conductor models. METHODS: The present study applied dipole source localization and current density reconstruction within individual realistically shaped head models to median nerve SEPs obtained during explorative finger movements. RESULTS: The SEPs associated with movement of the stimulated hand showed a minor reduction of the N20 amplitude and a markedly reduced amplitude for the frontal N30 and parietal P27, exhibiting a residual frontal negativity around 25 ms. The brain-stem P14 remained unchanged. Mapping of the different SEPs (movement of the non-stimulated hand minus movement of the stimulated hand) showed a bipolar field pattern with a maximum around 30 ms post-stimulus. In eight out of ten normal subjects, both the N30 and the gN30 (subtraction data) sources resided within the pre-central gyrus, more medially than the post-centrally located N20. Two subjects, in contrast, showed rather post-centrally localized sources in this time range. A model of the cortical SEP sources is introduced, explaining the data with respect to previously described findings of dipole localization, and from lesion studies and the alterations seen in motor diseases. CONCLUSIONS: The results provide evidence for a pre-central N30 generator, predominantly tangentially oriented, located within the motor cortex, while no sources were detected elsewhere. It is suggested that the mechanisms underlying the 'gating' effect during explorative finger movements in the 30 ms time range predominantly arise in the motor cortex.