Simultaneous side effects of both clozapine and valproate.
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Adult↗
Biomedical subjects
R W Keunen
Publications and source records attributed to R W Keunen.
Motor and somatosensory evoked potentials in asymptomatic spondylotic cord compression.
To assess whether electrophysiological tests are of use in differentiating between patients with asymptomatic cervical stenosis and patients with clinical evidence of myelopathy, we studied motor evoked potentials (MEPs) to magnetic brain stimulation and somatosensory evoked potentials (SEPs) in patients with asymptomatic cervical cord compression and compared the results to healthy age-matched controls. The MEPs were normal in 23 of 25 patients and SEPs in 22 of 23 patients. Thus, MEPs and SEPs are normal in most cases of asymptomatic cervical stenosis. As previous studies have shown MEPs, and to a lesser extent SEPs, to be sensitive in the detection of spondylotic myelopathy, our data indicate that MEP and SEP may be clinically useful for differentiating patients with cervical stenosis who have myelopathy from those who have not.
Adult↗
Nonlinear analysis of EEG in septic encephalopathy.
Electroencephalograms (EEG) were recorded in fourteen patients who experienced a severe septic encephalopathy (SE). EEG analysis included visual inspection, spectral analysis and a recently developed nonlinear analysis (the Kaplan test). All EEGs showed decreased fast activity and an increase of slow wave activity on visual inspection. There was a nonsignificant trend of negative correlation between the spectral EEG analysis and the severity of the acute systemic illness (based on the sum score of 14 variables known as APACHE II score) (standard coefficient = -0.43, p = 0.118). However, a much more pronounced and significant negative correlation was observed between the Kaplan test and the APACHE II score (standard coefficient = -0.94, p = 0.005). The EEG abnormalities seen in these patients were independent of the sedation level. Neither the EEG parameters, nor the APACHE II score, predicted outcome. Nonlinear analysis is more powerful than spectral analysis to extract clinical relevant information from EEGs in patients who experience a severe SE. The nonlinear EEG analysis suggest that brain dynamics in SE may be characterized by a shift into a fundamentally different level of cortical information exchange which can be summarized in nonlinear terminology as a loss of deterministic structure in the EEG.
APACHE↗
Modeling the temporal fluctuations of the cerebral blood flow velocity waveforms using surrogate data testing.
The objective of this study is to find out which mathematical model best explains the temporal fluctuations of the axial blood flow velocity waveforms in the basal arteries of the brain. Blood flow velocity time series were sampled by transcranial Doppler (TCD) examination of the middle cerebral arteries in 10 healthy volunteers. A recently developed mathematical test (surrogate data analysis) was used to examine whether the spectral Doppler maximum waveform consistent with some prespecified model (null hypothesis). We tested four different null hypothesis. 1. Uncorrelated white noise. 2. Linearly filtered noise. 3. Linearly filtered noise with a static nonlinear amplitude transformation. 4. Noisy nonlinear limit cycle. All null hypotheses except the last one could be rejected. We conclude that the TCD waveforms are best described as nonlinear limit cycle with some percentage of noise, either dynamical and/or observational, which is uncorrelated from one single oscillation to the next. These results are a strong argument to perform nonlinear analysis in future TCD studies in order to obtain a better understanding of the cerebral hemodynamics.
Adult↗
A transcranial Doppler study of basilar hemodynamics in progressive carotid artery disease.
In carotid artery disease (CAD) the basilar artery (BA) may act as an important intracranial collateral to supply hypoperfused middle cerebral artery (MCA) territories. Transcranial Doppler studies were performed to study the dependency between BA hemodynamics in relation to the MCA perfusion status. BA and MCA blood flow velocities (BFV), pulsatility indices (API) and cerebrovascular reactivity (CVR) were assessed in 40 patients with a progressive MCA hypoperfusion due to progressive CAD. All patients had patent cervical segments of their vertebral arteries with an antegrade vertebral flow profile. Duplex studies were performed to diagnose the severity of CAD. Hypoperfusion of the MCA was diagnosed by the degree of vasoparalysis assessed by a Diamox procedure. Analysis showed that the basilar BFV significantly increased in cases of progressive CAD, the basilar PI decreased but the basilar CVR remained unchanged. However, in cases of bilateral hemodynamic significant CAD and bilateral exhausted CVR in the MCA territory, the basilar artery did not exhibit an increase of BFVs or a decrease of the basilar PI, but the basilar CVR showed a significant decrease. Basilar artery CVR is not impaired if this artery has a function as intracranial collateral in CAD. However in cases of bilateral hypoperfused MCA territories the basilar artery does not function as a collateral pathway. The basilar CVR declines under these circumstances which merely reflects the exhausted hemodynamics in the anterior/posterior borderzones. This situation might lead to an increased stroke risk in the distal basilar supply zones.
Adult↗
Preliminary report of detecting microembolic signals in transcranial Doppler time series with nonlinear forecasting.
BACKGROUND AND PURPOSE: Most algorithms used for automatic detection of microembolic signals (MES) are based on power spectral analysis of the Doppler shift. However, controversies exist as to whether these algorithms can replace the human expert. Therefore, a different algorithm was applied that takes advantage of the periodicity of the MES. This so-called nonlinear forecasting (NLF) is able to detect periodicity in a time series, and it is hypothesized that this technique has the potential to detect MES. Moreover, because of the lack of prominent periodicity in both the normal Doppler signals (DS) and movement artifacts (MA), the NLF has a potential to differentiate MES from normal blood flow variations and MA. METHODS: Twenty single MES and 100 MA were selected by 2 human experts. NLF was applied to MES and MA and compared with 200 randomly chosen DS. NLF resulted in a so-called prediction value that ranges from + 1 in signals with prominent periodicity to 0 in signals that lack periodicity. RESULTS: NLF revealed that MES are more predictable than the normal Doppler signals (prediction [MES]=0.829+/-0.084 versus prediction [DS]= -0.060+/-0.228; P<0.0001). Moreover, MES are more predictable than the MA (prediction [MA]=-0.034+/-0.223; P<0.0001). No difference in prediction could be found between DS and MA. CONCLUSIONS: This preliminary report shows that MES can be separated from DS and MA by NLF. Research is needed as to whether this technology can be further developed for automatic detection of MES.
Artifacts↗
Nonlinear dynamical analysis of periodic lateralized epileptiform discharges.
Nonlinear time series analysis can be used to investigate the dynamics underlying the generation of EEG signal. In the present study we used this approach to study the pathophysiology of PLEDs. We calculated the correlation dimension D2 of an EEG with typical PLEDs, and compared the results with those obtained for surrogate data. These surrogate data have the same power spectrum and amplitude distribution as the original EEG data, but are otherwise random. By construction, such surrogate data can be described by a linear model. Our results showed that D2 estimations for PLEDs were low, on the order of one, and that the results for EEG and the surrogate data were clearly different, indicating that the EEG with PLEDs reflects nonlinear dynamics of the underlying neural networks.
Electroencephalography↗
Non-linear analysis of the electroencephalogram in Creutzfeldt-Jakob disease.
Creutzfeldt-Jakob disease is a rare, neurological, dementing disorder characterised by periodic sharp waves in the electroencephalogram (EEG). Non-linear analysis of these EEG changes may provide insight into the abnormal dynamics of cortical neural networks in this disorder. Babloyantz et al. have suggested that the periodic sharp waves reflect low-dimensional chaotic dynamics in the brain. In the present study this hypothesis was re-examined using newly developed techniques for non-linear time series analysis. We analysed the EEG of a patient with autopsy-proven Creutzfeldt-Jakob disease using the method of non-linear forecasting as introduced by Sugihara and May, and we tested for non-linearity with amplitude-adjusted, phase-randomised surrogate data. Two epochs with generalised periodic sharp waves showed clear evidence for non-linearity. These epochs could be predicted better and further ahead in time than most of the irregular background activity. Testing against cycle-randomised surrogate data and close inspection of the periodograms showed that the non-linearity of the periodic sharp waves may be better explained by quasi-periodicity than by low-dimensional chaos. The EEG further displayed at least one example of a sudden, large qualitative change in the dynamics, highly suggestive of a bifurcation. The presence of quasi-periodicity and bifurcations strongly argues for the use of a non-linear model to describe the EEG in Creutzfeldt-Jakob disease.
Creutzfeldt-Jakob Syndrome↗
The electroencephalogram during normal third trimester pregnancy and six months postpartum.
In 1942 Gibbs and Reid described a slowing of the electroencephalogram (EEG) at the end of a normal pregnancy. To the best of our knowledge this is the only report that addresses the modification of the EEG in normal pregnancy. We performed a spectral multichannel EEG analysis and revealed no differences during third trimester pregnancy and six months postpartum. Therefore EEG changes seen during pregnancy, which were previously regarded as 'subtle changes of pregnancy', may turn out to be clinically relevant changes which indicate either pre-existing EEG dysfunction or EEG abnormalities in the context of a pregnancy-related disorder.
Analysis of Variance↗
Cerebral vasospasm and vasodilatation in pre-eclampsia.
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Adult↗
Nonlinear transcranial Doppler analysis demonstrates age-related changes of cerebral hemodynamics.
We studied the age- and gender-related changes in complexity of arterial blood flow by analyzing the maximum velocity waveforms. Data were collected by insonation of the middle cerebral artery blood flow by a 2-MHz transcranial pulsed Doppler system. Following the paradigm of nonlinear dynamical systems or "chaos" theory, complexity is best evaluated by estimating the correlation dimension (D2) and the largest Lyapunov exponent (lambda 1). Forty healthy persons (male/female ratio: 1/1; mean age 48.6 y; range 19-86 y) were studied. No gender-related differences were observed. The age-effect showed a diminishing lambda 1 [df(1, 36) = 5.687; p < 0.022] and an increasing D2 at higher age [df(1, 36) = 4.997; p < 0.032]. The age-related decline of the lambda 1 implies a more prominent periodicity, explained by reduced fluctuations in R-R intervals and an altered gain of the baroreceptor reflex. The increased D2 might be related to more prominent vessel wall oscillations due to the increased vessel wall stiffness at higher age.
Adult↗
Rejection of the 'filtered noise' hypothesis to explain the variability of transcranial Doppler signals: a comparison of original TCD data with Gaussian-scaled phase randomized surrogate data sets.
Until the last few years the correlation dimension (D2) or the Lyapunow exponent were the two dominant mathematical methods which were applied to identify possible chaotic behavior in biological systems. Detection of deterministic chaos is important, because it suggests that a relatively simple nonlinear model might explain the data. It was however discovered that these methods could give rise to an erroneous detection of chaos. For this reason a new method was proposed in which the originally measured data set was directly compared with a computer generated 'surrogate' data set with exactly the same linear correlations as the original. The basic idea is then to compute a nonlinear statistic for the original data and for each of the surrogate data sets. In principle any statistic can be used. We used the correlation dimension (D2), which measures the complexity of a time series. In this study we applied this surrogate method to estimate whether the variability of the transcranial Doppler (TCD) waveforms is the result of nonlinearity or not. From 10 healthy volunteers, left middle cerebral artery (MCA) blood flow velocities were measured by TCD examinations. An artifact free epoch of each TCD was used for analysis. From each original data set 50 surrogate data sets were constructed using the Gaussian-scaled phase-randomized Fourier transform. For both the original and the surrogate data sets the D2 was measured. The D2 values of the original TCD waveforms differed significantly from the mean D2 of the surrogate data sets. Therefore the null hypothesis, which stated that the original TCD time series arise from filtered noise, is rejected and nonlinearity is detected. The clinical significance and implications are discussed.
Adult↗
Transcranial Doppler and systemic hemodynamic studies in septic shock.
The present study outlines the relationship between cerebral and systemic hemodynamics in patients with septic shock. Sepsis is an immune mediated systemic disease in which the systemic vascular resistance (SVR) often decreases as a result of a Gram negative sepsis. The result is a hyperdynamic systemic circulation with redistribution phenomena in different organ systems. In order to study the effect of sepsis on cerebral vessels 20 patients with septic shock (12 men, 8 women, mean age 57.9 years) were subjected to both pulmonary artery catheter and transcranial Doppler (TCD) monitoring. The data were correlated to the APACHE II score and outcome. The study showed that cerebral mean and end-diastolic blood flow velocities (BFV) in the middle cerebral arteries significantly enhanced if the SVR-index decreases. In some patients a severely reduced SVRI (below 500 dynes.s/cm5.m2) was observed in combination with a downstroke latent steal phenomenon. TCD abnormalities were strongly related to disease severity and outcome. The increased BFV are explained by a mild vasospasm of the basal cerebral arteries. TCD appears to be a valuable tool to monitor the cerebral hemodynamics in these patients. They are particularly at risk for ischemic brain damage if they are subjected to therapeutic or spontaneous hyperventilation, which can potentially be detected by TCD.
APACHE↗
Investigation of EEG non-linearity in dementia and Parkinson's disease.
Many recent studies based on the surrogate data method failed to identify significant non-linearity in the EEG. In this study we examine whether the use of a different embedding method (spatial instead of time delay), and calculation of Kolmogorov entropy (K2) and the largest Lyapunov exponent (L1) in addition to the correlation dimension (D2), can distinguish the EEG form linearly filtered noise. We have calculated D2, L1 and K2 of original EEG epochs and surrogate (phase randomized) data in 9 control subjects, 9 demented patients and 13 Parkinson patients. The correlation dimension D2 and the largest Lyapunov exponent L1 could distinguish between the EEG tracings and the surrogate data. Demented patients had significantly lower D2 and L1 compared to controls. L1 was higher in Parkinson patients than in demented patients. Contrary to other studies that have used the Theiler surrogate data method, we find evidence for non-linearity in normal and abnormal EEG during the awake/eyes closed state. Apparently it is the spatial structure in the EEG that exhibits much of the non-linear structure. Furthermore, non-linear EEG measures show more or less specific patterns of dysfunction in dementia and Parkinson's disease.
Aged↗
Monitoring intracranial dynamics by transcranial Doppler--a new Doppler index: trans systolic time.
Since the introduction of transcranial Doppler sonography (TCD) several investigators have described the relationship between raised intracranial pressure (ICP) and Doppler waveform. This waveform has been expressed by several indices, such as the pulsatility index (PI) and the resistance index (RI). These indices are used to demonstrate the presence of raised ICP. In childhood hydrocephalus this information can be used to indicate the need for shunt implantation. However, PI and RI do prove to have certain disadvantages as both are strongly influenced by the heart rate. Moreover, both indices have a broad range of reference values, especially in children. Therefore, they are not very reliable for detecting insidious changes in the ICP. These drawbacks are due to the fact that these indices are composed of blood flow velocity measurements and do not embody the slope of the TCD waveform itself. An ideal TCD waveform analysis should be performed concerning the time-related changes of the velocities. We present a hydrodynamic model, with its electrical analogue, which shows the effects of raised ICP on the intracranial hemodynamic system. Based on these physical findings we define a new Doppler index, the Trans Systolic Time, reflecting specific changes in the TCD waveform induced by changes in the mean ICP. The applicability of this index, compared with PI and RI, is illustrated by consecutive simultaneous TCD and AFP measurements in three children with hydrocephalus.
Blood Flow Velocity↗
The physiological and clinical significance of nonlinear TCD waveform analysis in occlusive cerebrovascular disease.
In order to compare the results of nonlinear analysis of hemodynamically compromised and noncompromised cerebral circulations we measured consecutive transcranial Doppler (TCD) waveforms of fourteen patients with a unilateral or bilateral occlusion of the internal carotid artery. The cerebral vasomotor reactivity (VMR) to acetazolamide in both middle cerebral artery (MCA) territories was established by using TCD. Conventional TCD data and nonlinear TCD analysis of data were compared. Nonlinear analysis of the TCD time series suggested dynamical chaos based on the fractal dimension of the TCD curve and the positive Lyapunov exponents in the compromised and noncompromised MCA territories. In the areas with the compromised circulation the positive Lyapunov exponents were significantly lower compared to the noncompromised side and in some cases with a negative VMR, the Lyapunov exponent was almost zero. The latter is suggestive for periodic behavior of the impaired cerebral circulation instead of the dynamical chaos which is found under normal conditions. The TCD time series of a hemodynamic compromised cerebral territory not only shows phenomena related to a decreased perfusion pressure (such as a 'damped waveform') but also phenomena which are related to a more prominent periodicity. We speculate that conventional and nonlinear TCD analysis could be used to determine the VMR.
Aged↗
Transcranial magnetic stimulation in patients with cervical spondylotic myelopathy: clinical and radiological correlations.
Motor evoked potentials (MEPs) were studied in 28 patients with cervical spondylotic myelopathy. MEPs after cortical stimulation were abnormal in 27 patients, the responses in the leg muscles being affected the most often. Clinically asymptomatic motor lesions were detected in 7 patients (25%). The central motor conduction time (CMCT) for the abductor digiti minimi muscles correlated significantly with the clinical disability, whereas the radiological findings did not correlate with the clinical and neurophysiological parameters. In 9 patients MEPs were also recorded in the biceps muscles. The 7 patients with an abnormal CMCT for the biceps muscles had the most severe stenosis at the C-4-C-5 level or higher. The 2 patients with normal MEPs of the biceps muscles both had a stenosis at the C-5-C-6 level. The results of this study suggest that MEPs are useful for detecting spinal cord dysfunction and for localizing the level of the lesion. Some recommendations regarding the possible use of MEPs in the clinical evaluation of patients with cervical spondylotic myelopathy are given.
Adult↗
Non-linear dynamical analysis of multichannel EEG: clinical applications in dementia and Parkinson's disease.
The irregular, aperiodic character of the EEG is usually explained by a stochastic model. In this view the EEG is linearly filtered noise. According to chaos theory such irregular signals can also result from low dimensional deterministic chaos. In this case the underlying dynamics is nonlinear, and has only few effective degrees of freedom. In contrast, stochastic models are less efficient, because they require in principle infinite degrees of freedom. Chaotic dynamics in the EEG can be studied by calculating the correlation dimension (D2). Although it has become clear that D2 calculations alone cannot prove chaos, the D2 has potential value as an EEG diagnostic. In this study we investigated whether D2 could be used to discriminate EEGs from normal controls, demented patients and Parkinson patients. We have analyzed epochs (20 channels; 2.5 s) from 52 EEGs (20 controls; 15 patients with dementia; 17 patients with Parkinson's disease). Controls had a mean D2 of 6.5 (0.9); demented patients of 4.4 (1.5), and Parkinson patients of 5.3 (0.9). Both groups were significantly different from controls (p < 0.001). There was a significant positive correlation between D2 and relative power in the beta band (r = 0.81) and a significant negative correlation between D2 and power in the delta (r = -0.60) and theta band (r = -0.37). These results suggest the possible usefulness of multichannel D2 estimation in a clinical setting.
Aged↗