Cortical regional hyperperfusion in nonconvulsive status epilepticus measured by dynamic brain perfusion CT.

BACKGROUND AND PURPOSE: Nonconvulsive status epilepticus (NCSE) is associated with a mortality rate of up to 18%, therefore requiring prompt diagnosis and treatment. Our aim was to evaluate the diagnostic value of perfusion CT (PCT) in the differential diagnosis of NCSE versus postictal states in patients presenting with persistent altered mental states after a preceding epileptic seizure. We hypothesized that regional cortical hyperperfusion can be measured by PCT in patients with NCSE, whereas it is not present in postictal states. MATERIALS AND METHODS: Nineteen patients with persistent altered mental status after a preceding epileptic seizure underwent PCT and electroencephalography (EEG). Patients were stratified as presenting with NCSE (n = 9) or a postictal state (n = 10) on the basis of clinical history and EEG data. Quantitative and visual analysis of the perfusion maps was performed. RESULTS: Patients during NCSE had significantly increased regional cerebral blood flow (P > .0001), increased regional cerebral blood volume (P > .001), and decreased (P > .001) mean transit time compared with the postictal state. Regional cortical hyperperfusion was depicted in 7/9 of patients with NCSE by ad hoc analysis of parametric perfusion maps during emergency conditions but was not a feature of postictal states. The areas of hyperperfusion were concordant with transient clinical symptoms and EEG topography in all cases. CONCLUSIONS: Visual analysis of perfusion maps detected regional hyperperfusion in NCSE with a sensitivity of 78%. The broad availability and short processing time of PCT in an emergency situation is a benefit compared with EEG. Consequently, the use of PCT in epilepsy may accelerate the diagnosis of NCSE. PCT may qualify as a complementary diagnostic tool to EEG in patients with persistent altered mental state after a preceding seizure.

Identification of brain structures involved in micturition with functional magnetic resonance imaging (fMRI).

OBJECTIVE: The voluntary control of micturition is believed to be integrated by complex interactions among the brainstem, subcortical areas and cortical areas. Several brain imaging studies using positron emission tomography (PET) have demonstrated that frontal brain areas, the limbic system, the pons and the premotor cortical areas were involved. However, the cortical and subcortical brain areas have not yet been precisely identified and their exact function is not yet completely understood. MATERIALS AND METHODS: This study used functional magnetic resonance imaging (fMRI) to compare brain activity during passive filling and emptying of the bladder. A cathetherism of the bladder was performed in seven healthy subjects (one man and six right-handed women). During scanning, the bladder was alternatively filled and emptied at a constant rate with bladder rincing solution. RESULTS: Comparison between passive filling of the bladder and emptying of the bladder showed an increased brain activity in the right inferior frontal gyrus, cerebellum, symmetrically in the operculum and mesial frontal. Subcortical areas were not evaluated. CONCLUSIONS: Our results suggest that several cortical brain areas are involved in the regulation of micturition.

Screening for sleep disorders in community pharmacies--evaluation of a campaign in Switzerland.

BACKGROUND: In 2003 the Swiss federation of pharmacists organized a campaign "sleep disturbances--daytime sleepiness". The goal was to assist pharmacy clients in detecting likely causes of any sleep disturbance or daytime sleepiness through a free of charge screening, and to deliver targeted counselling. For pharmacy practice there are no screening or triage guidelines to assess the severity of sleep and wakefulness disturbances and potential causes for those disturbances. In this paper the outcome of the campaign in terms of feasibility, participation, observed response patterns, sale of over-the-counter (OTC) sleeping pills, and counselling activities is evaluated. METHODS: The Stanford sleep disorders questionnaire and the Epworth sleepiness scale served to identify patterns of symptoms suggestive of four major categories of sleep disorders. The questionnaires were posted on a web-site and the clients' data were entered online in the pharmacies. A report was automatically generated and immediately available online to the pharmacists. The pharmacists documented separately their counselling activities in a pharmacist's activity report. RESULTS: Six hundred and twenty-two (23%) of 2743 pharmacy clients had response patterns suggestive of obstructive sleep apnoea, 418 (15%) of restless-legs-syndrome, 39 (1%) of a sleep disorder potentially associated with a psychiatric condition and 79 (3%) of narcolepsy. An Epworth sleepiness score >10 points was found in 567 (21%). After screening, 2345 (86%) pharmacy clients received targeted counselling. Only 216 (8%) purchased an OTC sleeping pill and 704 (26%) were recommended to consult a physician, but of these, 446 (63%) were already under medical supervision. CONCLUSIONS: The online screening tool for sleep disorders and daytime sleepiness was successfully introduced in Swiss pharmacies. Pharmacies were able to assess the pattern of individual sleep disorders and to identify a possible cause in nearly one-third of the cases.

Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls.

BACKGROUND AND AIMS: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI). PATIENTS AND METHODS: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal). RESULTS: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS-C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain. CONCLUSIONS: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.

Cerebrovascular response to repetitive visual stimulation in interictal migraine with aura.

Cortical hypersensitivity and absent habituation to different stimuli have been observed in migraine patients. These features might also be transmitted to the cerebral vasoreactivity, but results are conflicting so far. Transcranial Doppler ultrasound (TCD) was used to assess cerebral blood flow velocity (CBFV) changes in the middle (MCA) and posterior cerebral arteries (PCA) in relation to repetitive checkerboard visual stimulation. Stimulation consisted of 10 consecutive cycles, each comprising 10 s stimulation and 10 s rest. TCD recordings were analysed using stimulus-related averaging algorithm. Data of 19 interictal migraineurs with aura were compared to those of 19 headache-free healthy volunteers. The CBFV increase in PCA and in MCA during visual stimulation was significantly larger and steeper in migraineurs than in controls (P = 0.017 and P = 0.005). The response in PCA remained stable over the 10 stimulation cycles, both in migraineurs and in controls. The response in MCA was stable only in migraineurs. In controls it decreased over the last 5 stimulation cycles compared with the first 5 cycles (P = 0.04). Migraineurs with aura exhibit a larger cerebrovascular response to repetitive visual stimulation compared to headache-free subjects. A reduced adaptation to environmental stimuli in migraine is suggested, since there was no habituation in migraineurs in contrast to healthy controls.

Multiresolution fuzzy clustering of functional MRI data.

Recent developments in the analysis of functional MRI data reveal a shift from hypothesis-driven statistical tests to unsupervised strategies. One of the most promising approaches is the fuzzy clustering algorithm (FCA), whose potential to detect activation patterns has already been demonstrated. But the FCA suffers from three drawbacks: first the computational complexity, second the higher sensitivity to noise and third the dependence on the random initialization. With the multiresolution approach presented here, these weak points are significantly improved, as is demonstrated in our tests with simulated and real functional MRI data.

Whole-brain functional magnetic resonance imaging of cerebral arteriovenous malformations involving the motor pathways.

To investigate cortical, basal ganglia and cerebellar activation in patients with arteriovenous malformations (AVMs) involving the motor pathways, we studied ten patients (six male, four female, mean age 30.3 years, range 7.4-44.1) by whole-brain functional magnetic resonance imaging (fMRI) in a 1.5-T scanner with the EPI-BOLD-technique. In seven cases multiple fMRI studies were available, acquired in the course of the multi-session endovascular interventional treatment. Self-paced right- and left-handed finger-tapping tasks were used to invoke activation. In six patients a super-selective amytal test (Wada test) was performed during diagnostic pre-interventional angiography studies. Abnormal cortical activation patterns, with activation of the primary sensorimotor area, the supplementary motor area and/or the cerebellum shifted to unphysiological locations, were found in four patients. In all cases, localization of the AVM could account for the changes from the normal. After endovascular procedures, fMRI demonstrated shifts in the activation pattern in three patients. In the six patients that had undergone fMRI studies and the Wada test, both methods yielded comparable results. The fact that AVMs are structural anomalies for which the brain can partly compensate ('plasticity') was underlined by these results. fMRI is a valuable tool in the pre-therapeutic evaluation and post-interventional follow-up of patients with cerebral AVMs in whom an operation or an endovascular procedure is planned.

Damage to the parietal lobe impairs bimanual coordination.

Moving the upper limbs at a common tempo according to a mirror or parallel mode represents elementary coordination dynamics. Previously, the role of the medial wall areas have been emphasized for successful production of these bimanual patterns. The involvement of the parietal lobe is less clear despite its importance for the representation of motor skill and sensorimotor integration. The objective of this study was to investigate temporal control in patients with parietal pathology when performing isofrequency configurations. As compared to control subjects, these patients showed desynchronization of movement trajectories that was most apparent during parallel patterns. These observations suggest the significant role of the parietal lobe for bimanual coordination which becomes increasingly relevant as a function of task complexity.

Functional organisation of the saccadic reference system processing extraretinal signals in humans.

In order to investigate the neuronal network involved in processing extraretinal signals, functional magnetic resonance imaging (fMRI) was applied to subjects performing the double step saccade paradigm. There, the calculation of the amplitude of the second saccade must rely on extraretinal signals of the first. When compared to a task where both saccades could be performed by means of retinal signals alone, a parieto-frontal cortical network was activated, including lateral intraparietal area, precuneus, insula, inferior frontal gyrus and anterior cingulum.

Different ipsilateral representations for distal and proximal movements in the sensorimotor cortex: activation and deactivation patterns.

Each hemisphere is known to be also involved in controlling the ipsilateral arm, but with an asymmetry favoring the dominant hemisphere. However, the relative role of primary and secondary motor areas in ipsilateral control is not well defined. We used whole brain functional magnetic resonance imaging in healthy human subjects to differentiate between contributions from primary and secondary areas during discrete unilateral distal finger and proximal shoulder movements. It was found that ipsilateral distal movements activated secondary areas only, while sparing or even significantly deactivating the primary sensorimotor cortex. Ipsilateral proximal movements substantially activated both SM1 and secondary areas. A newly defined small territory within the precentral gyrus, extending from the premotor cortex and intruding toward SM1, showed an activation pattern corresponding to secondary motor areas. Finally, the effects of hemispheric dominance were confirmed, but attributed exclusively to secondary areas. These new imaging findings agree well with functional requirements as well as established anatomical and neurophysiological data.

Role of the corpus callosum in bimanual coordination: a comparison of patients with congenital and acquired callosal damage.

The objective of the study was to investigate temporal control in patients with congenital as compared to acquired pathology of the corpus callosum during two different bimanual paradigms: (i) a drawer-opening task during which one hand opened a drawer while the other hand reached and grasped a small object, and (ii) rhythmical circling movements that were executed according to the in-phase or antiphase mode. Synchronization values revealed that patients with acquired callosal dysfunction generally showed optimal behaviour during the goal-directed and familiar drawer-opening task but demonstrated strong tendencies towards desynchronization during circling movements, which became most apparent for antiphase coordination. Whereas one patient with callosal agenesis showed a similar performance, the other acallosal patients performed both activities successfully. These observations indicate that patients with congenital absence of the corpus callosum can make use of compensatory mechanisms for allowing temporal synchronization during bimanual movements whereas patients with acquired callosal dysfunction are severely hampered when the task places significant demands on the control processes. The data also underline that the ability of callosal patients to precisely time events in coordinated actions depend on the task constraints.

Skin and muscle vasomotor reflexes in detecting autonomic dysfunction in leprosy.

There are few tests to assess the function of small unmyelinated nerve fibers. One established test is the skin vasomotor reflex (SVMR), which uses laser doppler flow velocimetry. The SVMR has the disadvantages of being susceptible to interference (from change of temperature and alerting stimuli) and of requiring expensive equipment. An ultrasound doppler method, which is less expensive, can be used to detect muscle vasomotor reflex (MVMR) activity. We sought to compare the efficacy of these two methods in detecting dysfunction of small unmyelinated nerve fibers in patients with leprosy. SVMR was shown to be less sensitive (P < 0.01) and specific (P < 0.001) than MVMR. The favorable results of MVMR may be attributed to its lesser susceptibility to interfering sympathetic vasoconstriction from alerting stimuli. MVMR also reflects larger areas of blood vessel innervation than the laser doppler method. In leprosy, nerve damage is typically patchy and may be missed by the smaller sampling of the laser method.

Unwarping of unidirectionally distorted EPI images.

Echo-planar imaging (EPI) is a fast nuclear magnetic resonance imaging (MRI) method. Unfortunately, local magnetic field inhomogeneities induced mainly by the subject's presence cause significant geometrical distortion, predominantly along the phase-encoding direction, which must be undone to allow for meaningful further processing. So far, this aspect has been too often neglected. In this paper, we suggest a new approach using an algorithm specifically developed for the automatic registration of distorted EPI images with corresponding anatomically correct MRI images. We model the deformation field with splines, which gives us a great deal of flexibility, while comprising the affine transform as a special case. The registration criterion is least squares. Interestingly, the complexity of its evaluation does not depend on the resolution of the control grid. The spline model gives us good accuracy thanks to its high approximation order. The short support of splines leads to a fast algorithm. A multiresolution approach yields robustness and additional speedup. The algorithm was tested on real as well as synthetic data, and the results were compared with a manual method. A wavelet-based Sobolev-type random deformation generator was developed for testing purposes. A blind test indicates that the proposed automatic method is faster, more reliable, and more precise than the manual one.

[Aphasia research and speech localization in the brain]. / Zur Geschichte der Aphasiologie und Sprachlokalisation im Gehirn.

Aphasia research has become an acknowledged branch of modern cognitive neuropsychology research whose aim is to explore more fully the structures of knowledge and of cerebral processes which might both be affected in patients with aphasia. Up to the second half of this century, a model based on a specific cerebral localisation of language processes had emerged based on brain localisation research by Broca and Wernicke (among others). New modern neuroimaging techniques, however, such as computed tomography and magnetic resonance imaging (MRI), but also functional imaging modalities such as positron emission tomography or functional MRI, have modified these concepts. It emerges that in comprehension as well as in production of language, not only a few well defined centres are responsible for the activity, but there is a synchronised activity in large neuronal networks connecting various regions located both in the cortex and in the deep subcortical structures; today, this activity can be demonstrated best in a non-invasive and reproducible way with functional MRI.

Eye-hand coordination in uni- and bimanual goal-oriented tasks.

Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300+/-39 ms for the predictive condition versus 394+/-53 ms for the non-predictive condition, P<0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.

Functional organisation of saccades and antisaccades in the frontal lobe in humans: a study with echo planar functional magnetic resonance imaging.

The cortical activation pattern of saccades and antisaccades (versus rest) in the frontal lobe was analysed using an echo planar imaging (EPI) technique in 10 healthy subjects. Statistical analysis of activity in the dorsolateral prefrontal cortex disclosed a significantly greater activation during antisaccades in this region than during saccades. On the other hand, activity in the frontal eye fields was not statistically different in both tasks. These results confirm the important role of the dorsolateral prefrontal cortex for the correct performance of antisaccades obtained by studies in humans with isolated lesions of the dorsolateral prefrontal cortex.

Transoccipital power-based color-coded duplex sonography of cerebral sinuses and veins.

BACKGROUND AND PURPOSE: Power-based transcranial color-coded duplex sonography is a new development for cerebrovascular imaging that is suited for detection of slow velocities. The purpose of this study was to evaluate the ability of this technique to detect cerebral sinuses and veins by means of the occipital window and to provide reference data. METHODS: The straight and inferior sagittal sinuses, great and internal cerebral veins, and basal veins were insonated in 120 normal subjects. The number of identified vessels, peak systolic (PSV) and end-diastolic (PDV) velocities, and resistance indices were determined. RESULTS: In subjects aged 20 to 59 years, straight sinuses were identified in 81% and great and internal cerebral veins in 34%. In subjects aged 60 to 79 years, straight sinuses were detected in 50%, great cerebral veins in 20%, and internal cerebral veins in 13%. All insonated inferior sagittal sinuses and basal veins were missed. Velocities were highest in straight sinuses (PSV, 35 [7 to 64] cm/s; PDV, 23 [2 to 43] cm/s), slower in great cerebral veins (PSV, 23 [12 to 34] cm/s; PDV, 16 [7 to 26] cm/s), and slowest in internal cerebral veins (PSV, 14 [10 to 18] cm/s; PDV, 10 [5 to 15] cm/s) (mean with 95% confidence intervals [CIs]). Straight sinus velocities decreased with age for PSV (20 to 39 years, 40 [7 to 73] cm/s; 60 to 79 years, 28 [9 to 46] cm/s; P < .01) and PDV values (20 to 39 years, 28 [4 to 52] cm/s; 60 to 79 years, 16 [5 to 26] cm/s; P < .001) (mean with 95% CIs) and were higher in women than men in the group aged 20 to 39 years. (P < .05). Resistance indices increased with age in the straight sinus (20 to 39 years, 0.30 [0.18 to 0.42]; 60 to 79 years, 0.42 [0.31 to 0.53]; P < .001) (mean with 95% CIs). CONCLUSIONS: Transoccipital power-based color-coded duplex sonography enabled imaging and velocity measurements in the straight sinus of subjects aged 20 to 59 years. In elder subjects detection rate of the straight sinus decreased, and it was low for deep cerebral veins in all age groups.

Human cortical plasticity: functional recovery with mirror movements.

Cortical plasticity of the human brain permits functional recovery after brain injury even in the absence of neuronal recovery. We report the combined evaluation, including electrophysiology and functional magnetic resonance imaging, of the pattern of cortical and cerebellar reorganization, in a patient with mirror movements as a sequel of perinatal unilateral brain injury. Recovery resulted in motor control by the healthy hemisphere using direct ipsilateral corticospinal projections and the contralateral cerebellum.

Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings.

Vitamin B12 deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Lack of vitamin B12 in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. We report the case of a 14(1)/2-month-old child of strictly vegetarian parents who presented with severe psychomotor retardation. This severely hypotonic child had anemia due to insufficient maternal intake of vitamin B12 with associated megaloblastic anemia. MRI of the brain revealed severe brain atrophy with signs of retarded myelination, the frontal and temporal lobes being most severely affected. It was concluded that this myelination retardation was due to insufficient intake of vitamin B12 and vitamin B12 therapy was instituted. The patient responded well with improvement of clinical and imaging abnormalities. We stress the importance of MRI in the diagnosis and follow-up of patients with suspected diseases of myelination.