Acute myelopathy of unknown aetiology: a clinical, neurophysiological and MRI study of short- and long-term prognostic factors.

Brain and spinal cord magnetic resonance imaging (MRI), multimodal evoked potentials (EPs) and cerebrospinal fluid (CSF) analysis were performed in 27 patients with acute myelopathy of unknown aetiology (AMUA), to detect the diagnostic and prognostic values of paraclinical tests at presentation. Spinal cord MRI was abnormal in 56% and brain MRI in 33% of the patients. Visual EPs were abnormal in 7%, median somatosensory EPs in 17%, tibial somatosensory EPs in 56% and motor EPs in 35% of the cases examined. Brain-stem acoustic EPs were normal in all the patients. CSF oligoclonal bands (OBs) were detected in 30% of cases. The patients were divided into subgroups according to the short-term clinical outcome (complete, partial or absent recovery). There were no significant differences among the three groups as regards MRI findings. Patients with complete recovery showed a significantly lower frequency of tibial somatosensory EP and motor EP abnormalities. According to the paraclinical findings at onset and on the basis of a long-term clinical follow-up (mean duration 24 months), 6 patients were diagnosed as having clinically definite multiple sclerosis, while 21 did not develop further neurological disturbances. Only the presence of CSF OBs was significantly more frequent in patients with definite multiple sclerosis. Our study indicates that EPs exploring spinal cord function are more powerful than spinal MRI for predicting the short-term outcome of AMUA, while the combined use of brain MRI and CSF OBs has the highest negative predictive value for the subsequent development of clinically definite multiple sclerosis.

Acute- and insidious-onset myelopathy of undetermined aetiology: contribution of paraclinical tests to the diagnosis of multiple sclerosis.

Brain magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid examination were performed in 42 patients with myelopathy of undetermined aetiology in order to detect abnormalities usually related to multiple sclerosis (MS). Patients were divided into three groups: insidious-onset myelopathy with only motor signs (group A; 11 patients), with both motor and sensory signs (group B; 18 patients) and acute-onset myelopathy (group C; 13 patients). Multiple brain MRI lesions were found in 18 patients (2 of group A, 13 of group B and 3 of group C). Another 7 patients had a single white-matter lesion. Visual EPs were abnormal in 21 and brain-stem auditory EPs in 12 patients. Paraclinical tests supported the diagnosis of MS in 25 patients (60%) by showing subclinical brain abnormalities. Oligoclonal bands were found in 16 of these 25 patients. The findings strongly suggest a diagnosis of MS in the patients of group B.

Correlation between multimodal evoked potentials and magnetic resonance imaging in multiple sclerosis.

Sixty multiple sclerosis (MS) patients (33 definite, 13 probale and 14 suspected were investigated by computed tomography (CT), magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid (CSF) electrophoresis. MRI abnormalities were found in 50 cases, while at least one abnormal evoked potential was detected in each of 52 cases. Brain-stem auditory evoked potentials were more sensitive than MRI for the detection of brain-stem involvement. All the patients with oligoclonal bands had abnormal MRI and none of the patients with normal MRI had oligoclonal bands in the CSF. The number and the extent of MRI lesions were significantly correlated with the duration of disease and with the degree of disability. Our observations stress the importance of the combined use of MRI and EPs in detecting silent CNS lesions in MS patients.

Event-related brain potentials: laplacian transformation for multichannel time-frequency analysis.

During a visual-motor task the movement strategies and the learning processes are investigated. A group of 10 normal young volunteers underwent the experiment. The EEG signal was recorded through the 10-20 acquisition system during the execution of a task after a visual input. Each subject repeated the movement several times in three different conditions: i) without knowledge of the performance; ii) with visual feedback; iii) with knowledge of the result. The signal was transformed through Laplacian operator in order to eliminate the spurious coherence and then time-variant coherence was calculated. Different trends of the coherence function have been evidenced in subjects learning and not learning the better movement strategy. In particular, relations have been found between frontal, central and occipital electrodes in medium and high frequency ranges.

Total and partial coherence analysis of spontaneous and evoked EEG by means of multi-variable autoregressive processing.

The joint use of total and partial coherence between pairs of EEGs simultaneously recorded in a standard set, is shown to enhance what is caused by direct correlation between cortical subsystems and what is instead related to the spread of the electromagnetic field. A multi-variable autoregressive approach is employed in the computation, giving results even for a very short time window, thus allowing coherence to be investigated at the main cortical latencies of evoked potentials. In particular, when a combined visual and somatosensory stimulation is applied, cortical interactions are captured in the frequency domain.

Non-invasive multielectrode array for high resolution sampling of scalp-recorded potential fields.

A new non-invasive electrode array has been devised to record electrical signals on the scalp. The electrodes are arranged every 10 mm in a 4 x 8 grid, thus totalling 32. Electrical coupling is assured by a column of conductor gel with a diameter of 2 mm. The electrode array has been used to record multichannel scalp potentials evoked by stimulation of the median nerve at the wrist. It was positioned on the parietal region with the midline corresponding to the external acoustic meatus. The high spatial resolution of this device allows a detailed spatial sampling of the scalp potential field where the electrical activity arising from the parietal and premotor cortex is predominant. Scalp potentials with the system are compared with those with the 10/20 system. The improved spatial resolution allows more precise localization of minimum and maximum of the potential field, though the overall distortion introduced by aliasing in the 10/20 system is not striking. Instead, the amplitudes of the fields are considerably affected by insufficient spatial sampling.

Temporal segmentation and multiple-source analysis of short-latency median nerve SEPs.

Short-latency (10-50 ms) median nerve somatosensory evoked potentials (SEPs) from four normal subjects were analysed by means of temporal segmentation techniques and source derivation methods. In each case the responses were recorded using 32 electrodes. Dipolar optimization was carried out with a time-varying technique, using three different approaches: regional source estimation, spherical source estimation (one radial and one tangential component), and multiple dipolar approach. This was to assess the relative influence on the dipolar solution of the different optimization techniques. The effect of the different number of channels in the estimation procedures has been also investigated. The methods of optimization are crucial, particularly for the orientation of P22. In all cases the source location estimated with the 32-electrode montage was shifted towards the centre of the spheres.

Analysis of temporal non-stationarities in EEG signals by means of parametric modelling.

A method for the analysis of variability of EEG signals is described. We examined simulated signals and real EEGs obtained from a normal subject and two epileptic patients. The first step of the method is based on autoregressive (AR) modelling of short EEG epochs. Prediction coefficients of the AR model were computed as a function of time from partially-overlapping moving windows of 2 s duration. The temporal behaviour of these coefficients was analysed to detect variability: quasi-stationary activity causes only smooth changes in the coefficients while variations in the amplitude and/or the frequency content of the signal are shown to produce sharp changes in the coefficients. A segmentation algorithm was developed to detect and quantify with a numerical value (Difference Measure, DM) the AR coefficients variations.

Focal abnormalities of P3 ERPs unveiled in patients with cortical lesions and primary progressive aphasia by average reference recordings.

Event related potentials (ERPs) to an auditory odd-ball paradigm were recorded with the linked earlobe reference (LER) and with a computer calculated average reference (AR), excluding the two linked earlobe derivations. The study was performed in 30 patients with lesions of frontal, parietal, occipital cortex, unilateral and bilateral lesions of the medial temporal lobe (MTL), in four patients affected by Primary Progressive Aphasia (PPA) and in 56 age matched controls. Latencies, amplitudes and scalp distribution of the earlier ERP components (P1, N1, P2, N2) were within normal limits for both LER and AR recordings. P3 scalp distribution in patients was normal when LER was used, with the exception of two patients affected by bilateral MTL lesions. When P3 was recorded using AR, the scalp distribution was statistically different from normal distributions in all patients. A negativity, instead of the positive P3 observed in controls, was recorded in patients from leads corresponding to the affected areas. This finding might have clinical applications, and confirms earlier studies suggesting that P3 is generated simultaneously from different cortical areas.

Assessment of visual function in MS patients: comparative study of some diagnostic tests.

Optic pathways are frequently involved in Multiple Sclerosis (MS). However, in some cases the involvement is asymptomatic or gives rise to only slight visual disturbances without alterations of visual acuity or of clinically evident visual field defects. In these cases several diagnostic tests permit an objective evaluation of the visual dysfunction. The aim of this study is to compare the value of contrast sensitivity test (CST), pattern reversal visual evoked potential (VEP), ophthalmoscopy, Goldmann perimetry in 45 MS patients with normal visual acuity. Examination of contrast sensitivity was carried out with a simple two-alternative forced choice test estimating the spatial frequency of 4 cycles/degree. The VEP was performed with a pattern reversal checkerboard at a spatial frequency of 1 and 2 cycles/degree. Fundus examination was abnormal in 12 patients; visual field defects were detected in 16 patients. 32 patients (71.1%) had abnormal CST in one or both eyes. VEP for the 30' checks was abnormal in 32 cases (71.1%) and that for the 15' checks in 36 cases (80.0%). All but 4 patients (91.2%) had one or more abnormal tests. All patients with abnormal perimetry and/or fundus examination had also CST and/or VEP altered. It is apparent that CST and VEP reveal a significant proportion of abnormalities in the visual system that have not been revealed by routine neuroophthalmological examination.

P300 asymmetries in focal brain lesions are reference dependent.

In 6 patients with lesions of frontal, parietal and temporal lobe, in 4 patients affected by primary progressive aphasia (PPA) and in 56 age-matched controls, event-related potentials (ERPs) to an auditory odd-ball paradigm were recorded with the linked earlobe reference (LER) and with a computer calculated average reference (AR), excluding the two linked earlobe derivations. Latencies, amplitudes and scalp distribution of the earlier ERP components (P1, N1, P2, N2) were within normal limits for both LER and AR recordings. P300 scalp distribution in patients was normal when LER was used. When P300 was recorded using AR, the scalp distribution was statistically different from normal distributions in all patients. A negativity, instead of the positive P300 observed in controls, was recorded in patients from leads corresponding to the affected hemisphere.

Measuring evoked responses in multiple sclerosis.

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.

FFT approximation in Alzheimer's disease.

The electroencephalographic modifications that occur during the course of Alzheimer's disease are characterised by an increase in the potential of low frequency bands, a diminution in the potential of alpha activity, and a change in the topographical distribution of the potential of all band frequencies. In this study, the fast Fourier transform (FFT) approximation was used to characterise modifications in the electroencephalogram location or orientation of the source of the dipole equivalent of the delta, theta, alpha1, alpha2, beta1 and beta2 frequencies in 20 with patients with Alzheimer's disease and in a control group of 20 age-matched subjects. A statistical (t-test) comparison of the two groups revealed a significant change in the location of the dipolar source along the vertical axis in 18 (90%) of the patients; this change involved all the frequency bands. There was also a significant movement of the dipolar source of the alpha1 band towards the anterior regions. In addition, the control group showed that there was a significant correlation between age and a more surface expression of the source of the delta, theta, alpha1 and beta1 bands.

EEG coherence in Alzheimer's disease.

EEG coherence can be used to evaluate the functionality of cortical connections and to get information about the synchronization of the regional cortical activity. We studied EEG coherence in patients affected by clinically probable Alzheimer's disease (AD) in order to quantify the modifications in the cortico-cortical or cortico-subcortical connections. The EEGs were recorded in 10 AD patients (with mild or moderate degrees of dementia) and in 10 normal age-matched subjects, at rest and eye-closed, from 16 electrodes with linked-ears reference. Spectral parameters and coherence were calculated by a multichannel autoregressive model using 50 artifact-free epochs, 1 s duration each. Alpha coherence was significantly decreased in 6 patients, the decrease being more accentuated in the area near the electrode taken into account; a significant delta coherence increase was found in a few patients between frontal and posterior regions. The AD group showed a significant decrease of alpha band coherence, in particular in temporo-parieto-occipital areas, more evident in patients with a more severe cognitive impairment. These abnormalities could reflect two different pathophysiological changes: the alpha coherence decrease could be related to alterations in cortico-cortical connections, whereas the delta coherence increase could be related to the lack of influence of subcortical cholinergic structures on cortical electrical activity.

Neurophysiological and cognitive markers of disease evolution in multiple sclerosis.

Both evoked potentials and cognitive tests may provide useful information which cannot be derived from the clinical observation. For this reason, there have been some attempts to use EPs in monitoring the natural history of the disease and in assessing the efficacy of therapeutic trials. However, no conclusion can be derived from the few available data. Although MRI is more sensitive than EPs in revealing new lesions in brain, cerebellum and brainstem, EPs are more sensitive in revealing optic nerve and spinal cord lesions. Moreover, the poor relationship between brain MRI abnormalities and disability has raised the possibility that cognitive evaluation may be an additional sensitive marker of brain involvement over time. Since the gold standard for the assessment of disease activity is uncertain, it is therefore advisable that frequent MRI, EPs and cognitive assessment may integrate clinical outcomes measured by conventional scales, both in the study of the natural disease course and in monitoring clinical trials.

Clinical, neurophysiological, and magnetic resonance imaging correlations in multiple sclerosis.

Magnetic resonance imaging (MRI) has a pivotal role in diagnosis of multiple sclerosis and is being increasingly used as a paraclinical measure to assess treatment efficacy in clinical trials. However, the correlations between clinical and MRI findings in patients with multiple sclerosis are weak and, therefore, newer MR techniques are being developed to increase both MRI sensitivity for detecting disease activity and its pathological specificity for better assessing disease evolution. Evoked potentials (EPs) can be used to confirm the diagnosis of multiple sclerosis and their abnormalities are correlated with symptoms and signs referable to involvement of the corresponding nervous pathways. However, their use is limited when assessing disease progression and monitoring clinical trials in multiple sclerosis. Both magnetic resonance imaging (MRI) and evoked potentials (EPs) provide information which cannot be obtained by clinical evaluation, especially for assessing disease activity. Nevertheless, both these paraclinical techniques cannot substitute for clinical measures of disability when assessing disease progression and monitoring phase III clinical trials in multiple sclerosis.

Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings.

OBJECTIVE: To explore functional corticocortical connections in multiple sclerosis by means of coherence of the EEG, and to evaluate their correlations with the degree of cognitive impairment and with brain lesion load assessed by MRI. METHODS: EEG coherence was studied from 28 patients with clinically definite multiple sclerosis. Ten minutes of resting EEG were recorded with 20 scalp electrodes, with binaural reference. FFT power and coherence were calculated in artifact free epochs of 1 second and compared with values from 22 control subjects of comparable age and sex distribution. Patients also underwent MRI (n=27) and neuropsychological examination (n=21). RESULTS: Compared with controls, patients with multiple sclerosis showed increased theta power in the frontotemporal-central regions (p<0.005). theta Band coherence was decreased between homologous areas (p<0.02). alpha Band coherence was decreased both in the local and long distance connections (p<0.0005). These findings were most striking both in patients with high MRI subcortical lesion load and in patients with cognitive involvement. A significant correlation was found between interhemispheric theta (p=0.02) and alpha (p=0. 017) and anteroposterior alpha (p=0.013) coherence and subcortical MRI lesion load, but not with exclusively periventricular lesion load. CONCLUSIONS: These findings support the hypothesis that cognitive impairment in multiple sclerosis is mostly dependent on involvement of corticocortical connections related to demyelination and/or axonal loss within the white matter immediately underlying the cortex.

Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis.

Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients with benign multiple sclerosis and 13 patients with secondary progressive multiple sclerosis, matched for age and duration of the disease, to investigate the nature of the disability in multiple sclerosis. Patients with secondary progressive multiple sclerosis had significantly greater lesion loads for five of seven periventricular regions and for three of nine regions separate from the ventricles. Patients with secondary progressive multiple sclerosis also had more severe infratentorial atrophy scores (p = 0.04), whereas there were no differences between the two groups in number and extent of enhancing lesions. The frequencies were significantly higher and severities greater for multimodal EP abnormalities of all the modalities in patients with secondary progressive multiple sclerosis. At least one EP component was absent in 12 (92%) patients with secondary progressive multiple sclerosis but in only one patient (8%) with benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for cervical cord involvement in eight (61%) patients with secondary progressive multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These data indicate that the total amount of lesions, the distribution, and the nature of the pathological process might all account for the development of disability in multiple sclerosis.

Comparison between magnetic resonance imaging and other techniques in 39 multiple sclerosis patients.

Till now there are no specific laboratory tests to confirm the diagnosis of Multiple Sclerosis (MS). For this reason the diagnosis of MS is based on the clinical evidence of central nervous system white matter disease with temporal and spatial dissemination of the lesions. Recent advances in neurophysiology and imaging techniques can provide more objective criteria towards more accurate and earlier diagnosis, detecting clinically unsuspected lesions. We evaluated 39 MS patients (23 definite, 7 probable, 9 possible) by Magnetic Resonance Imaging (MRI), CT scan, Evoked Potentials (EPs) testing and Cerebrospinal Fluid analysis. MRI was abnormal in 34 cases (87%) and CT scan in 14 (36%); EPs were also abnormal in 34 cases. 30 patients had both EPs and MRI alterated and 4 patients had alterated only one of the two investigations. The frequency of EPs alterations was: VEP 74%, Median SEP 44%, Tibial SEP 59% and BAEP 54%. The BAEP was more sensitive than MRI in detecting brainstem involvement. On the other hand MRI was more sensitive than SEPs in detecting somatosensory pathways involvement. The combined use of the two techniques allowed a reclassification of 10 out of 16 possible or probable MS cases.