Characterization of motor and somatosensory function for stroke patients.

In a pilot study, stroke patients with a lesion related to the motor system were studied using magnetoencephalography (MEG) and electromyography (EMG). The patients performed sustained finger movements for 30 s followed by 30 s of rest and 20 repetitions of this sequence in total. Task-related cortical signals derived from MEG were observed here at very different frequency scales. Slow signals below 0.1 Hz were extracted by independent component analysis and are associated with the sustained activation of the motor cortex, the dcMEG motor activation. MEG-EMG coupling phenomena in the 10-30 Hz range were analyzed using the imaginary part of coherency and are attributed to cortico-muscular coupling driving the muscles. Additionally a signal from the somatosensory cortex due to an electrical stimulation at the wrist, the N20m, was recorded as a physiological marker. Field maps and time series associated with the three types of signals are presented for one patient and one control subject as the signal quality of the patient data was not sufficient to achieve a group result. The feasibility of a comprehensive electrophysiological measuring and analysis procedure of the motor function for stroke research is demonstrated by the results.

Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit.

OBJECTIVE: To determine the extent that demographics, clinical characteristics, comorbidities, and complications contribute to the risk of in-hospital mortality and morbidity in acute stroke. METHODS: Data of consecutive patients admitted to 14 stroke units cooperating within the Berlin Stroke Register were analyzed. The association of demographics, clinical characteristics, comorbidities, and complications with the risk of in-hospital death and poor outcome at discharge was assessed, and independent attributable risks were calculated, applying average sequential attributable fractions. RESULTS: In a 3-year period, 16,518 consecutive patients with ischemic or hemorrhagic stroke were documented. In-hospital mortality was 5.4%, and 45.7% had a poor outcome (modifed Rankin Scale score ≥3). In patients with length of stay (LOS) ≤7 days, 37.5% of in-hospital deaths were attributed to stroke severity, 23.1% to sociodemographics (age and prestroke disability), and 28.9% to increased intracranial pressure (iICP) and other complications. In those with LOS >7 days, age and stroke severity accounted for 44.1%, whereas pneumonia (12.2%), other complications (12.6%), and iICP (8.3%) contributed to one-third of in-hospital deaths. For poor outcome, attributable risks were similar for prestroke disability, stroke severity, pneumonia, and other complications regardless of the patient's LOS. CONCLUSIONS: Approximately two-thirds of early death and poor outcome in acute stroke is attributed to nonmodifiable predictors, whereas main modifiable factors are early complications such as iICP, pneumonia, or other complications, on which stroke unit treatment should focus to further improve the prognosis of acute stroke.

[Neurotuberculosis: a continuing clinical challenge]. / Neurotuberkulose : Eine anhaltende klinische Herausforderung.

In Germany neurotuberculosis is quite rare. Familiarity with the disease is nonetheless important because of many differential diagnoses and therapeutic implications. The diagnosis of neurotuberculosis is made by considering of clinical presentation, CSF, and cerebral imaging. Early diagnosis, prompt initiation of effective antitubercular therapy, and clinical staging are necessary for establishing a long-term treatment prognosis. The results of neurotuberculosis therapy are often unsatisfactory despite the availability of effective drugs. Lasting damage or death can be averted in fewer than half of the patients. Studies now confirm that early adjuvant corticoid therapy reduces lethality and morbidity. Resistant new strains of the pathogen, Mycobacterium tuberculosis, complicate therapy. Recent discoveries especially in diagnosis and therapy are explained using case evidence.

DC-magnetoencephalography and time-resolved near-infrared spectroscopy combined to study neuronal and vascular brain responses.

The temporal relation between vascular and neuronal responses of the brain to external stimuli is not precisely known. For a better understanding of the neuro-vascular coupling changes in cerebral blood volume and oxygenation have to be measured simultaneously with neuronal currents. With this motivation modulation dc-magnetoencephalography was combined with multi-channel time-resolved near-infrared spectroscopy to simultaneously monitor neuronal and vascular parameters on a scale of seconds. Here, the technique is described, how magnetic and optical signals can be measured simultaneously. In a simple motor activation paradigm (alternating 30 s of finger movement with 30 s of rest for 40 min) both signals were recorded non-invasively over the motor cortex of eight subjects. The off-line averaged signals from both modalities showed distinct stimulation related changes. By plotting changes in oxy- or deoxyhaemoglobin as a function of magnetic field a characteristic trajectory was created, which was similar to a hysteresis loop. A parametric analysis allowed quantitative results regarding the timing of coupling: the vascular signal increased significantly slower than the neuronal signal.

The discovery of slowness--recent progress in DC-MEG research.

The non-invasive electrical recording of Direct Current (DC) phenomena in the frequency range below 0.1 Hz, e.g., occurring in metabolic injuries to brain cells in stroke or migraine (anoxic depolarization, peri-infarct depolarization, spreading depression), is technically restricted due to large drift artifacts caused by electrochemical instabilities at the electrode-skin interface. This limitation could be overcome by invasive approaches only. However, as early as 1969 first magnetic fields in this frequency range have been recorded over the human torso by oscillating the subject vertically in front of a magnetic field detector using a see-saw. By this technique the DC field is conversed to a higher frequency, where the external noise level is less. In the last decade, the modulation based DC-magnetoencephalography (DC-MEG) has been methodically refined, which allowed monitoring low-amplitude magnetic fields in this frequency domain arising not only from injured tissue, but also generated by functional cortical activation. Furthermore, the combination of DC-MEG and NearInfraRed Spectroscopy (NIRS) opens up a new avenue to study cortical neurovascular coupling, as vascular and neuronal activations could be analyzed simultaneously even without averaging in a single-trial mode. Recordings inside the novel magnetically shielded room (BMSR-2 of the Physikalisch-Technische Bundesanstalt, Berlin) exhibiting an extremely low background noise level in the DC frequency range, and alleviating the need of sensor-to-source modulation, allow to resolve additionally the short-term (subsecond) dynamics of neuronal DC-processes.

Tracing of proximal lumbosacral nerve conduction--a comparison of simultaneous magneto- and electroneurography.

OBJECTIVE: The reconstruction of nerve impulse conduction along proximal lumbosacral plexus and nerve roots is compared using simultaneous magneto- and electroneurography. METHODS: In 3 healthy subjects the left tibial nerve was electrostimulated at the ankle. Evoked magnetic fields and electric surface potentials were measured simultaneously over the lumbosacral spine using a multichannel SQUID-detector with a planar measuring area and 25 surface electrodes covering a comparable area centered around L4. Based on either magnetic field or electric potential maps the depolarization front of the evoked compound action currents (CAC) was spatio-temporally reconstructed using a simple equivalent current dipole model in a half-space volume conductor. RESULTS: The mean signal-to-noise ratio in the magnetic (electric) recordings was around 4 (8). Yet, the localization quality for the propagating CAC was lower for electric than magnetic recordings. The local nerve conduction velocity was around 47 m/s (calculated from magnetic data), but fluctuated unphysiologically for electric data. CONCLUSION: In comparison to electroneurography, an anatomically reasonable localization of evoked compound action currents propagating in lumbosacral roots can be obtained by magnetoneurography.

Non-invasive single-trial monitoring of human movement-related brain activation based on DC-magnetoencephalography.

Neuroimaging techniques, such as fMRI, PET and near-infrared spectroscopy, monitor task-related neuronal activations in the brain indirectly through the associated neurovascular/metabolic responses. To assess the primary neuronal activations directly, magnetoencephalography was combined here with a mechanical modulation of the head-to-sensor position and signal separation via independent component analysis. In all of five subjects this approach allowed to monitor the time evolution of DC fields (<0.1 Hz) over the left hemisphere related to complex finger movements of the right hand alternating with rest periods (30 s each). Throughout the recording period of 30 min, stable task-related DC fields were recordable in a single-trial mode, i.e. without any averaging. DC-MEG opens up the possibility of analysing non-invasively cortical DC-activity also in stroke, migraine or epilepsy patients.

Magnetoneurography of evoked compound action currents in human cervical nerve roots.

OBJECTIVE: A measurement protocol for magnetoneurography (MNG) is established which allows the non-invasive localization and tracing of evoked compound action currents propagating along cervical nerve roots in man. METHODS: Inside a magnetically shielded room either both median or both ulnar nerves of healthy subjects were conventionally electrostimulated in alternation. Evoked magnetic responses were recorded using a multichannel SQUID-detector with a planar measuring area centered over the neck. Simultaneously, electric surface potentials were recorded using cervical bipolar electrode montages. RESULTS: Upon median (ulnar) nerve stimulation somatosensory evoked magnetic fields up to 20 fT (10 fT) amplitude were detected propagating over the cervical transforaminal root entry zone, with corresponding electrical surface potentials of 1.5 microV (0.5 microV). Furthermore, the signal-to-noise ratio of the spatiotemporal magnetic field mappings in median nerve stimulation experiments allowed dipolar source reconstructions and tracing of the propagation of the compound action currents along nerve root fibers. CONCLUSION: Magnetoneurography allows tracing of the propagation of evoked compound action currents along cervical roots in healthy subjects with millisecond temporal and high spatial resolution. Thus, MNG offers a sensitivity appropriate to serve as a clinical diagnostic tool for localizing focal neuropathies of cervical nerve roots.

Non-invasive magnetoneurography for 3D-monitoring of human compound action current propagation in deep brachial plexus.

Compound action current (CAC) propagation along nerve fibers running deep in the human brachial plexus was 3D-visualized based on non-invasive 49-channel superconducting quantum interference device (SQUID) magnetoneurography. Spatio-temporal mappings over the upper thoracal quadrant of magnetic fields (<100 fT) evoked upon alternating median and ulnar nerve stimulation in seven healthy volunteers showed consistently smoothly propagating dipolar patterns for both the CAC depolarization and repolarization phases. Multipolar current source reconstructions (i) distinguished spatially CAC propagation pathways along either median or ulnar plexus fibers, allowed (ii) to calculate local conduction velocities ( approximately 56 m/s) and (iii) even to estimate the CAC extension along the nerve fibers (depolarization phase: approximately 11 cm). Thus, for deep proximal nerve segments magnetoneurography can provide a detailed tracing of neural activity which is a prerequisite to localize non-invasively focal nerve malfunctions.

Independent component analysis of noninvasively recorded cortical magnetic DC-fields in humans.

We apply a recently developed multivariate statistical data analysis technique--so called blind source separation (BSS) by independent component analysis--to process magnetoencephalogram recordings of near-dc fields. The extraction of near-dc fields from MEG recordings has great relevance for medical applications since slowly varying dc-phenomena have been found, e.g., in cerebral anoxia and spreading depression in animals. Comparing several BSS approaches, it turns out that an algorithm based on temporal decorrelation successfully extracted a dc-component which was induced in the auditory cortex by presentation of music. The task is challenging because of the limited amount of available data and the corruption by outliers, which makes it an interesting real-world testbed for studying the robustness of ICA methods.

Rapid recovery (20 ms) of human 600 Hz electroencephalographic wavelets after double stimulation of sensory nerves.

Non-invasive scalp-recordings of human somatosensory evoked potentials (SEP) contain high-frequency (600 Hz) wavelet bursts, presumably generated by synchronized thalamocortical and/or intracortical population spikes. Here, double pulse stimulation (interval 20 ms) in 12 healthy subjects revealed significantly different burst recovery for mixed vs. sensory-only nerves. For median nerves the second burst response was decreased (11/11 subjects), possibly due to interfering reafferent (e.g. muscle spindle) input. In contrast, for sensory-only superficial radial nerves (containing less fibers than median nerves), weak bursts were detected in 6/11 subjects and were found fully recovered in 4/6 subjects. This potential for rapid burst recovery at 20 ms intervals renders contributions from neurons emitting bursts based on slowly recovering low-threshold calcium spikes unlikely and favors the generation of macroscopic SEP bursts by specialized cell populations, e.g. inhibitory interneurons and/or chattering cells the latter of which are capable to discharge rapidly repeating (50 Hz) high-frequency (600 Hz) bursts of fast sodium spikes.

Artifact reduction in magnetoneurography based on time-delayed second-order correlations.

Artifacts in magnetoneurography data due to endogenous biological noise sources, like the cardiac signal, can be four orders of magnitude higher than the signal of interest. Therefore, it is important to establish effective artifact reduction methods. We propose a blind source separation algorithm using only second-order temporal correlations for cleaning biomagnetic measurements of evoked responses in the peripheral nervous system. The algorithm showed its efficiency by eliminating disturbances originating from biological and technical noise sources and successfully extracting the signal of interest. This yields a significant improvement of the neuro-magnetic source analysis.

Non-invasive long-term recordings of cortical 'direct current' (DC-) activity in humans using magnetoencephalography.

Recently, biomagnetic fields below 0.1 Hz arising from nerve or muscle injury currents have been measured non-invasively using superconducting quantum interference devices (SQUIDs). Here we report first long-term recordings of cortical direct current (DC) fields in humans based on a horizontal modulation (0.4 Hz) of the body and, respectively, head position beneath the sensor array: near-DC fields with amplitudes between 90 and 540 fT were detected in 5/5 subjects over the auditory cortex throughout prolonged stimulation periods (here: 30 s) during which subjects were listening to concert music. These results prove the feasibility to record non-invasively low amplitude near-DC magnetic fields of the human brain and open the perspective for studies on DC-phenomena in stroke, such as anoxic depolarization or periinfarct depolarization, and in migraine patients.

Magnetometry of injury currents from human nerve and muscle specimens using superconducting quantum interferences devices.

Acute lesions of polarized membranes lead to slowly decaying ('near-DC') injury currents driven by the transmembrane resting potential gradient. Here we report the first recordings of injury-related near-DC magnetic fields from human nerve and muscle specimens in vitro using Superconducting Quantum Interference Devices (SQUIDs) operated in a conventional magnetically shielded room in a clinical environment. The specimen position was modulated sinusoidally beneath the sensor array by a non-magnetically fabricated scissors lift to improve the signal-to-noise ratio for near-DC fields. Depending on the specimen geometry the field patterns showed dipolar or quadrupolar aspects. The slow decay of human nerve and muscle injury currents was monitored for several hours from a distance of a few centimeters. Thus DC-magnetometry provides a sensitivity which might allow the remote detection of injury currents also in vivo.

Magnetoneurographic 3D localization of conduction blocks in patients with unilateral S1 root compression.

OBJECTIVES: Tibial nerve somatosensory evoked magnetic fields (tSEFs) over the lower back reflect the propagation of compound action currents along fibers of plexus, nerve roots and cauda equina. One clinical perspective for this 'magnetoneurography' is the non-invasive 3D localization of focal slowing or blocks of conduction. Here, first tSEF mappings in 3 consecutive patients with acute unilateral S1 nerve root compression are reported. METHODS: Right and left tibial nerves were electrostimulated in alternation; tSEF responses were recorded using a multichannel SQUID-detector; additionally, spinal and cortical SEP, F-wave and H-reflex studies were performed. RESULTS: In all patients an intraindividual side-to-side comparison of spinal tSEF mappings was obtained: using a dipolar source model compound action currents could be visualized propagating along plexus, nerve roots and cauda equina on the non-affected side whereas on the affected side normally-propagating dipolar field patterns could be recorded only distal to the spinal transforaminal root entrance; this reflects focal slowing or block of conduction in nerve root fibers as indicated by the SEP, F-wave and H-reflex study results. CONCLUSIONS: With a registration time of 15 min a 3D localization of proximal slowing or block of conduction was successfully performed in patients suffering from acute nerve root lesions.

fMRI assessment of somatotopy in human Brodmann area 3b by electrical finger stimulation.

Functional magnetic resonance imaging (fMRI) is capable of detecting focal brain activation induced by electrical stimulation of single fingers in human subjects. In eight subjects somatotopic arrangement of the second and fifth finger was found in Brodmann area 3b of the primary somatosensory cortex. In four subjects the representation area of the second finger was located lateral and inferior to the fifth finger; in one subject the somatotopy was reversed. In three subjects representation areas of the two fingers in Brodmann area 3b were found overlapping. Additional activated areas were found on the crown of ipsilateral and contralateral postcentral gyrus (Brodmann areas 1 and 2) and posterior parietal cortex.

Somatotopic source arrangement of 600 Hz oscillatory magnetic fields at the human primary somatosensory hand cortex.

Based on low-noise superconducting quantum interference devices (SQUIDs) magnetoencephalography allows the non-invasive detection of low-amplitude high-frequency brain responses evoked about 20 ms after electric hand nerve stimulation. The main spectral energy of these brief oscillatory bursts (near 600 Hz) is in the range typical for rapidly repeated action potentials. Here, the magnetic fields of median and ulnar nerve evoked 600 Hz bursts are shown to exhibit a somatotopic arrangement at the primary somatosensory hand cortex closely resembling that of the concomitant postsynaptic primary cortical response (¿N20m'). Two possible burst generators are discussed: (1) repetitive spike volleys conducted along the terminal segments of somatotopically arranged thalamocortical axons, and (2) early intracortical spike activity in nerve-specific subterritories of the 3b hand area.

Mapping of tibial nerve evoked magnetic fields over the lower spine.

Using a low-noise 49-channel dc-SQUID system spinal somatosensory evoked fields (SEF) were recorded which were generated by compound action currents evoked upon posterior tibial nerve stimulation. The SEF mapping showed the action current propagation along the sciatic nerve, lumbosacral plexus and cauda equina in parallel to simultaneously recorded electrical potentials (SEP). For a reliable intraindividual side-to-side comparison of spinal SEFs the right and left tibial nerves were stimulated in alternating order; this procedure minimizes artifactual inter-nerve SEF map differences due to eventual patient-to-sensor displacements which might occur in serial measurements. These large-area lumbar SEF mappings open up several clinical perspectives for magnetoneurography, in particular with respect to the 3D-localization of proximal conduction blocks.