I studied Medicine in Leiden and Applied Physics in Delft. In 2000, I got my PhD in Applied Physics from Delft, and registered as a clinical neurologist.
I’m heading the department of Clinical Neurophysiology of the Medisch Spectrum Twente, a large teaching hospital, and I chair Clinical Neurophysiology (CNPH) at the University of Twente (utwente.nl).
My research involves the pathophysiology of epilepsy, ischaemia, brain monitoring in the ICU, and fundamentals of EEG generation.
We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in... more We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin—Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales. We theoretically substantiate experimental observations of chloride influx generating cytotoxic edema, while sodium entry alone does not. We show a tipping point of Na /K-ATPase functioning, where below cell volume rapidly increases as a function of the remaining pump activity, and a Gibbs–Donnan-like equilibrium state is reached. This precludes a return to physiological conditions even when pump strength returns to baseline. However, when voltage-gated sodium channels are temporarily blocked, cell volume and membrane potential normalize, yielding a potential therapeutic strategy.
Abstract
Objective: In common peripheral neuropathies, sensory symptoms usually prevail over mot... more Abstract
Objective: In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This
predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.
Methods: We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials
(CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs
and CMAPs.
Results: Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean 6 standard deviation 3065 vs. 4666
minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in
strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all
more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent
Na+ conductance during continuing depolarisation.
Interpretation: Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with
faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster
depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be
attributed to differences in ion channel composition between sensory and motor axons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013
Spreading depolarization (SD) is an important phenomenon in stroke and migraine. However, the pro... more Spreading depolarization (SD) is an important phenomenon in stroke and migraine. However, the processes underlying the propagation of SD are still poorly understood, and an elementary model that is both physiological and quantitative is lacking. We show that, during the onset and propagation of SD, the concentration time courses of excitatory substances such as potassium and glutamate can be described with a reaction–diffusion equation. This equation contains four physiological parameters: (1) a concentration threshold for excitation; (2) a release rate; (3) a removal rate; and (4) an effective diffusion constant. Solving this equation yields expressions for the propagation velocity, concentration time courses, and the minimum stimulus that can trigger SD. This framework allows for analyzing experimental results in terms of these four parameters. The derived time courses are validated with measurements of potassium in rat brain tissue.
Received October 31, 2012.
Revision received January 30, 2013.
Accepted February 6, 2013.
This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle acti... more This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients. A crossover, placebo-controlled clinical trial was conducted in 10 patients. After administration of either a single dose of fluoxetine (20 mg) or a placebo, muscle activation of the lower arm was measured during maximum (isometric) force of the musculus flexor carpi radialis and musculus extensor carpi radialis. Delay times, grip strength, and Motricity Index were measured to assess functional ability. After fluoxetine intake, a significant increase in activation was found in both agonist and antagonist muscles of the paretic arm (P < 0.05). This increase did not influence the motor function. In this pilot study, it was found that fluoxetine influences motor output in chronic stroke patients. Therefore, fluoxetine may influence motor recovery after stroke. Additional studies have to be conducted to explore the effects of fluoxetine on motor recovery after stroke.
Stroke is a major cause of adult-onset disability and dependency. We investigated whether EEG par... more Stroke is a major cause of adult-onset disability and dependency. We investigated whether EEG parameters are of prognostic value for functional outcome 6 months after ischemic stroke.One-hundred and ten patients presenting with acute ischemic stroke and persistent neurological deficits at EEG recording were incrementally included. Clinical characteristics, volume of ischemia and EEG parameters were correlated with functional outcome assessed with the modified Rankin Scale (mRS) score. Predictive values for disability, dependency and death were calculated using receiver operating characteristic (ROC) curves and logistic regression modeling.The EEG pairwise derived Brain Symmetry Index (pdBSI) and (delta + theta)/(alpha + beta) ratio (DTABR) were significantly correlated with the modified Rankin Scale (mRS) score at month 6 (Spearman ρ = 0.46 and ρ = 0.47, respectively, p < 0.0005 for both). NIHSS (OR 1.15, 95% CI 1.04–1.27, p = 0.005) and pdBSI (OR 4.07, 95% CI 1.32–12.58, p = 0.015) were independently associated with disability 6 months after stroke. Dependency was independently indicated by NIHSS (OR 1.22, 95% CI 1.09–1.37, p < 0.0005) and DTABR (OR 2.25, 95% CI 1.16–4.37, p = 0.016). Six month mortality was independently indicated by age at stroke onset (OR 1.18, 95% CI 1.05–1.32, p = 0.007), NIHSS (OR 1.11, 95% CI 1.03–1.21, p = 0.009) and DTABR (OR 2.04, 95% CI 1.08–3.85, p = 0.028).EEG in the subacute setting of ischemic stroke may be of prognostic value for disability, dependency and death after 6 months.Early prognostication of functional outcome after stroke is relevant to efficient rehabilitation management to enhance recovery and minimize long-term disability.
Continuous EEG monitoring could benefit stroke patients as it may detect changes in brain functio... more Continuous EEG monitoring could benefit stroke patients as it may detect changes in brain function in a possible reversible state, allowing early intervention. The Brain Symmetry Index (BSI) was introduced previously as a measure to quantify ischemia in acute hemispheric stroke patients, and a positive correlation was found between the BSI and the National Institutes of Health Stroke Scale. Here, we explore the feasibility and potential clinical relevance of continuous EEG monitoring in acute hemispheric stroke, with the BSI as an indicator of the effect of thrombolysis with recombinant tissue plasminogen activator (r-tPA). Patients with acute hemispheric stroke treated with r-tPA were monitored using a bipolar eight channel EEG. The BSI is defined as the mean of the absolute value of the difference in the mean hemispheric amplitude spectrum; values range from 0 (no asymmetry) to 1 (maximal asymmetry). The clinical condition of the patients was assessed with the National Institutes of Health Stroke Scale. In this pilot study 16 patients were included. In all patients, the BSI remained constant or showed improvement during and after treatment with r-tPA. The correlation between the BSI and National Institutes of Health Stroke Scale in this study is significant, and confirms previous results. The correlation between the change in BSI and the change in National Institutes of Health Stroke Scale during treatment with r-tPA is significant, as well. No clinical significant complications occurred during r-tPA treatment. Our results show that continuous EEG monitoring using the BSI is technically feasible and provides real-time information about the effect of thrombolysis in acute hemispheric stroke patients.
Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other inv... more Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other invasive procedures. We used a swine model of CAGE to determine if quantitative electroencephalography (qEEG) is a useful tool in diagnosis and prognostication of CAGE.0.05 ml/kg of air was injected into the ascending pharyngeal artery in 16 pigs. Intracranial pressure, lactate in brain microdialysate and brain oxygen tension were measured during 4 h after embolization. The qEEG parameters mean amplitude (MAMP), alpha-delta ratio (ADR), spectral edge frequency (SEF90), spatial brain symmetry index (sBSI) and temporal brain symmetry index (tBSI) were calculated.MAMP and tBSI but not ADR, SEF90 and sBSI correlate with intracranial pressure, brain lactate and brain oxygen tension after 4 h. Early levels of MAMP and tBSI can predict intracranial pressure, brain lactate and brain oxygen tension after 4 h.MAMP and tBSI are sensitive for cerebral injury and can predict outcome in a swine model of CAGE.This study provides evidence for the utility of qEEG for diagnosis and prognosis in CAGE. Further studies are necessary to investigate the use of this method in patients.
We describe a previously healthy 48-year-old man who presented with clinical characteristics sugg... more We describe a previously healthy 48-year-old man who presented with clinical characteristics suggestive of internal carotid artery dissection, confirmed by magnetic resonance imaging. He developed a massive infarction of the left cerebral hemisphere and died after 3 days of transtentorial herniation. Post-mortem examination identified a dissection of the thoracic aorta caused by Erdheim-Gsell cystic medionecrosis, with the characteristic degeneration of the elastic fibers of the lamina media. The dissection showed an unusually large extension not only distally into both iliac arteries, but also proximally into both carotid arteries. To our knowledge, such an extensive dissection has not been described previously. Underlying vessel wall disorders of the aorta, such as Erdheim Gsell cystic medionecrosis, should be considered in young patients with spontaneous arterial dissection.
The objective of this review was to compare and to discuss the results of studies that investigat... more The objective of this review was to compare and to discuss the results of studies that investigated the ability of drugs to improve motor recovery after stroke by influencing dopamine, norepinephrine, or serotonin concentrations in the brain. A systematic literature search up to January 2009 was conducted in MEDLINE, Pubmed, EMBASE and in the database of the Cochrane Stroke Group Trial Register. In addition, the literature reference lists of the relevant publications were checked. The literature search was conducted in order to identify randomized controlled trials focusing on the effects of drugs on motor recovery after stroke. In order to structure the data, motor recovery was sub-divided into motor control and motor function. The methodological quality of the studies was also assessed. Six studies, investigating the effects of 7 different kinds of drugs were included. Methodological scores varied between 10 and 14 (max 19). Motor control was not influenced by any of the drugs. Motor function improved in patients treated with methylphenidate, trazodone, and nortriptyline. Results for fluoxetine and levodopa were contradicting. There is insufficient evidence to conclude that neuromodulating drugs targeting serotonin, norepinephrine, or dopamine influence motor recovery after stroke.
We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in... more We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin—Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales. We theoretically substantiate experimental observations of chloride influx generating cytotoxic edema, while sodium entry alone does not. We show a tipping point of Na /K-ATPase functioning, where below cell volume rapidly increases as a function of the remaining pump activity, and a Gibbs–Donnan-like equilibrium state is reached. This precludes a return to physiological conditions even when pump strength returns to baseline. However, when voltage-gated sodium channels are temporarily blocked, cell volume and membrane potential normalize, yielding a potential therapeutic strategy.
Abstract
Objective: In common peripheral neuropathies, sensory symptoms usually prevail over mot... more Abstract
Objective: In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This
predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.
Methods: We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials
(CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs
and CMAPs.
Results: Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean 6 standard deviation 3065 vs. 4666
minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in
strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all
more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent
Na+ conductance during continuing depolarisation.
Interpretation: Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with
faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster
depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be
attributed to differences in ion channel composition between sensory and motor axons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013
Spreading depolarization (SD) is an important phenomenon in stroke and migraine. However, the pro... more Spreading depolarization (SD) is an important phenomenon in stroke and migraine. However, the processes underlying the propagation of SD are still poorly understood, and an elementary model that is both physiological and quantitative is lacking. We show that, during the onset and propagation of SD, the concentration time courses of excitatory substances such as potassium and glutamate can be described with a reaction–diffusion equation. This equation contains four physiological parameters: (1) a concentration threshold for excitation; (2) a release rate; (3) a removal rate; and (4) an effective diffusion constant. Solving this equation yields expressions for the propagation velocity, concentration time courses, and the minimum stimulus that can trigger SD. This framework allows for analyzing experimental results in terms of these four parameters. The derived time courses are validated with measurements of potassium in rat brain tissue.
Received October 31, 2012.
Revision received January 30, 2013.
Accepted February 6, 2013.
This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle acti... more This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients. A crossover, placebo-controlled clinical trial was conducted in 10 patients. After administration of either a single dose of fluoxetine (20 mg) or a placebo, muscle activation of the lower arm was measured during maximum (isometric) force of the musculus flexor carpi radialis and musculus extensor carpi radialis. Delay times, grip strength, and Motricity Index were measured to assess functional ability. After fluoxetine intake, a significant increase in activation was found in both agonist and antagonist muscles of the paretic arm (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). This increase did not influence the motor function. In this pilot study, it was found that fluoxetine influences motor output in chronic stroke patients. Therefore, fluoxetine may influence motor recovery after stroke. Additional studies have to be conducted to explore the effects of fluoxetine on motor recovery after stroke.
Stroke is a major cause of adult-onset disability and dependency. We investigated whether EEG par... more Stroke is a major cause of adult-onset disability and dependency. We investigated whether EEG parameters are of prognostic value for functional outcome 6 months after ischemic stroke.One-hundred and ten patients presenting with acute ischemic stroke and persistent neurological deficits at EEG recording were incrementally included. Clinical characteristics, volume of ischemia and EEG parameters were correlated with functional outcome assessed with the modified Rankin Scale (mRS) score. Predictive values for disability, dependency and death were calculated using receiver operating characteristic (ROC) curves and logistic regression modeling.The EEG pairwise derived Brain Symmetry Index (pdBSI) and (delta + theta)/(alpha + beta) ratio (DTABR) were significantly correlated with the modified Rankin Scale (mRS) score at month 6 (Spearman ρ = 0.46 and ρ = 0.47, respectively, p < 0.0005 for both). NIHSS (OR 1.15, 95% CI 1.04–1.27, p = 0.005) and pdBSI (OR 4.07, 95% CI 1.32–12.58, p = 0.015) were independently associated with disability 6 months after stroke. Dependency was independently indicated by NIHSS (OR 1.22, 95% CI 1.09–1.37, p < 0.0005) and DTABR (OR 2.25, 95% CI 1.16–4.37, p = 0.016). Six month mortality was independently indicated by age at stroke onset (OR 1.18, 95% CI 1.05–1.32, p = 0.007), NIHSS (OR 1.11, 95% CI 1.03–1.21, p = 0.009) and DTABR (OR 2.04, 95% CI 1.08–3.85, p = 0.028).EEG in the subacute setting of ischemic stroke may be of prognostic value for disability, dependency and death after 6 months.Early prognostication of functional outcome after stroke is relevant to efficient rehabilitation management to enhance recovery and minimize long-term disability.
Continuous EEG monitoring could benefit stroke patients as it may detect changes in brain functio... more Continuous EEG monitoring could benefit stroke patients as it may detect changes in brain function in a possible reversible state, allowing early intervention. The Brain Symmetry Index (BSI) was introduced previously as a measure to quantify ischemia in acute hemispheric stroke patients, and a positive correlation was found between the BSI and the National Institutes of Health Stroke Scale. Here, we explore the feasibility and potential clinical relevance of continuous EEG monitoring in acute hemispheric stroke, with the BSI as an indicator of the effect of thrombolysis with recombinant tissue plasminogen activator (r-tPA). Patients with acute hemispheric stroke treated with r-tPA were monitored using a bipolar eight channel EEG. The BSI is defined as the mean of the absolute value of the difference in the mean hemispheric amplitude spectrum; values range from 0 (no asymmetry) to 1 (maximal asymmetry). The clinical condition of the patients was assessed with the National Institutes of Health Stroke Scale. In this pilot study 16 patients were included. In all patients, the BSI remained constant or showed improvement during and after treatment with r-tPA. The correlation between the BSI and National Institutes of Health Stroke Scale in this study is significant, and confirms previous results. The correlation between the change in BSI and the change in National Institutes of Health Stroke Scale during treatment with r-tPA is significant, as well. No clinical significant complications occurred during r-tPA treatment. Our results show that continuous EEG monitoring using the BSI is technically feasible and provides real-time information about the effect of thrombolysis in acute hemispheric stroke patients.
Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other inv... more Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other invasive procedures. We used a swine model of CAGE to determine if quantitative electroencephalography (qEEG) is a useful tool in diagnosis and prognostication of CAGE.0.05 ml/kg of air was injected into the ascending pharyngeal artery in 16 pigs. Intracranial pressure, lactate in brain microdialysate and brain oxygen tension were measured during 4 h after embolization. The qEEG parameters mean amplitude (MAMP), alpha-delta ratio (ADR), spectral edge frequency (SEF90), spatial brain symmetry index (sBSI) and temporal brain symmetry index (tBSI) were calculated.MAMP and tBSI but not ADR, SEF90 and sBSI correlate with intracranial pressure, brain lactate and brain oxygen tension after 4 h. Early levels of MAMP and tBSI can predict intracranial pressure, brain lactate and brain oxygen tension after 4 h.MAMP and tBSI are sensitive for cerebral injury and can predict outcome in a swine model of CAGE.This study provides evidence for the utility of qEEG for diagnosis and prognosis in CAGE. Further studies are necessary to investigate the use of this method in patients.
We describe a previously healthy 48-year-old man who presented with clinical characteristics sugg... more We describe a previously healthy 48-year-old man who presented with clinical characteristics suggestive of internal carotid artery dissection, confirmed by magnetic resonance imaging. He developed a massive infarction of the left cerebral hemisphere and died after 3 days of transtentorial herniation. Post-mortem examination identified a dissection of the thoracic aorta caused by Erdheim-Gsell cystic medionecrosis, with the characteristic degeneration of the elastic fibers of the lamina media. The dissection showed an unusually large extension not only distally into both iliac arteries, but also proximally into both carotid arteries. To our knowledge, such an extensive dissection has not been described previously. Underlying vessel wall disorders of the aorta, such as Erdheim Gsell cystic medionecrosis, should be considered in young patients with spontaneous arterial dissection.
The objective of this review was to compare and to discuss the results of studies that investigat... more The objective of this review was to compare and to discuss the results of studies that investigated the ability of drugs to improve motor recovery after stroke by influencing dopamine, norepinephrine, or serotonin concentrations in the brain. A systematic literature search up to January 2009 was conducted in MEDLINE, Pubmed, EMBASE and in the database of the Cochrane Stroke Group Trial Register. In addition, the literature reference lists of the relevant publications were checked. The literature search was conducted in order to identify randomized controlled trials focusing on the effects of drugs on motor recovery after stroke. In order to structure the data, motor recovery was sub-divided into motor control and motor function. The methodological quality of the studies was also assessed. Six studies, investigating the effects of 7 different kinds of drugs were included. Methodological scores varied between 10 and 14 (max 19). Motor control was not influenced by any of the drugs. Motor function improved in patients treated with methylphenidate, trazodone, and nortriptyline. Results for fluoxetine and levodopa were contradicting. There is insufficient evidence to conclude that neuromodulating drugs targeting serotonin, norepinephrine, or dopamine influence motor recovery after stroke.
To evaluate the value of continuous electroencephalography in early prognostication in patients t... more To evaluate the value of continuous electroencephalography in early prognostication in patients treated with hypothermia after cardiac arrest. Prospective cohort study. Medical intensive care unit. Sixty patients admitted to the intensive care unit for therapeutic hypothermia after cardiac arrest. None. In all patients, continuous electroencephalogram and daily somatosensory evoked potentials were recorded during the first 5 days of admission or until intensive care unit discharge. Neurological outcomes were based on each patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s best achieved Cerebral Performance Category score within 6 months. Twenty-seven of 56 patients (48%) achieved good neurological outcome (Cerebral Performance Category score 1-2).At 12 hrs after resuscitation, 43% of the patients with good neurological outcome showed continuous, diffuse slow electroencephalogram rhythms, whereas this was never observed in patients with poor outcome.The sensitivity for predicting poor neurological outcome of low-voltage and isoelectric electroencephalogram patterns 24 hrs after resuscitation was 40% (95% confidence interval 19%-64%) with a 100% specificity (confidence interval 86%-100%), whereas the sensitivity and specificity of absent somatosensory evoked potential responses during the first 24 hrs were 24% (confidence interval 10%-44%) and 100% (confidence interval: 87%-100%), respectively. The negative predictive value for poor outcome of low-voltage and isoelectric electroencephalogram patterns was 68% (confidence interval 50%-81%) compared to 55% (confidence interval 40%-60%) for bilateral somatosensory evoked potential absence, both with a positive predictive value of 100% (confidence interval 63%-100% and 59%-100% respectively). Burst-suppression patterns after 24 hrs were also associated with poor neurological outcome, but not inevitably so. In patients treated with hypothermia, electroencephalogram monitoring during the first 24 hrs after resuscitation can contribute to the prediction of both good and poor neurological outcome. Continuous patterns within 12 hrs predicted good outcome. Isoelectric or low-voltage electroencephalograms after 24 hrs predicted poor outcome with a sensitivity almost two times larger than bilateral absent somatosensory evoked potential responses.
The implementation of a computer assisted system for real-time classification of the electroencep... more The implementation of a computer assisted system for real-time classification of the electroencephalogram (EEG) in critically ill patients.Eight quantitative features were extracted from the raw EEG and combined into a single classifier. The system was trained with 41 EEG recordings and subsequently evaluated using an additional 20 recordings. Through visual analysis, each recording was assigned to one of the following categories: normal, iso-electric, low voltage, burst suppression, slowing, and EEGs with generalized periodic discharges or seizure activity.36 (88%) recordings from the training set and 17 (85%) recordings from the test set were classified correctly. A user interface was developed to present both trend-curves and a diagnostic output in text form. Implementation in a dedicated EEG monitor allowed real-time analysis in the intensive care unit (ICU) during pilot measurements in four patients.We present the first results from a computer assisted EEG interpretation system, based on a combination of eight quantitative features. Our system provided an initial, reasonably accurate interpretation by non-experts of the most common EEG patterns observed in neurological patients in the adult ICU.Computer assisted EEG monitoring may improve early detection of seizure activity and ischemia in critically ill patients.
Automated interpretation of clinical EEG recordings will reduce subjectivity and visual bias from... more Automated interpretation of clinical EEG recordings will reduce subjectivity and visual bias from analysis and can reduce the time required for interpretation. As a first step in the design of a fully automated system, a method is presented to characterize the main properties of the posterior dominant rhythm (PDR), in particular its frequency, symmetry and reactivity. The presented method searches for dominant peaks in the EEG spectra during eyes-closed states with a three-component curve-fitting technique. From the fitted curve, the frequency and amplitude are estimated. The symmetry and the reactivity are found using the spectral power at the PDR frequencies. In addition, a certainty value is introduced as a measure of confidence for each estimate. The method was evaluated on a test set of 1215 clinical EEG recordings and compared to the PDR frequencies obtained from the visual analysis, as reported in the diagnostic reports. The calculated PDR frequencies were within 1.2 Hz of the visual estimates in 92.5% of the cases. Even higher accuracies were reached when estimates with low certainty values were discarded. The presented method quantifies essential features of the PDR with a matched accuracy to visual inspection, making it a feasible contribution to the design of a fully automated interpretation system.► We introduce a method to automatically characterize the frequency, amplitude, symmetry and reactivity of the posterior dominant rhythm. ► A certainty value provides the clinician with a confidence score of each estimate. ► In more than 92.5% of the cases the PDR frequency was estimated within 1.2 Hz of visual estimates.
Carotid endarterectomy is a common procedure as a secondary prevention of stroke, and one of the ... more Carotid endarterectomy is a common procedure as a secondary prevention of stroke, and one of the early controversies in carotid surgery is centered around whether a shunt should be used during this procedure. Although various EEG parameters have been proposed to determine if the brain is at risk during carotid artery clamping, the common procedure is still the visual assessment of the EEG. We propose a brain symmetry index (BSI), that has been implemented as an on-line quantitative EEG parameter, as an additional criterion for shunt need in carotid endarterectomy. The BSI captures a particular asymmetry in spectral power between the two cerebral hemispheres, and is normalized between 0 (perfect symmetry) and 1 (maximal asymmetry). The index was evaluated retrospectively in a group of 57 operations in which the EEG and the transcranial Doppler were used as criteria for shunt insertion. In addition, after online implementation of the algorithm, several patients have been evaluated prospectively. If no visual EEG changes were detected, it was found that the change in BSI from baseline, DeltaBSI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=0.03 in all patients. In none of these patients shunting was performed, except for 11 in whom shunting was advised based on changes in the transcranial Doppler signal. None of these patients suffered from neurological complications. In those operations with visual EEG changes during test-clamping and selective shunting, we found that DeltaBSI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=0.06. In this group, one patient suffered from intraoperative stroke and one patient died, most likely from a hyperperfusion syndrome. The BSI may assist in the visual EEG analysis during carotid endarterectomy and provides a quantitative measure for electroencephalographic asymmetry due to cerebral hypo-perfusion. In patients with a change in the BSI (DeltaBSI) smaller than 0.03 during test clamping, visual EEG analysis showed no changes, whereas if visual EEG analysis did warrant shunting, it was found that DeltaBSI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=0.06.
This article presents a method to transform routine clinical EEG recordings to an alternative vis... more This article presents a method to transform routine clinical EEG recordings to an alternative visual domain. The method is intended to support the classic visual interpretation of the EEG background pattern and to facilitate communication about relevant EEG characteristics. In addition, it provides various quantitative features. The EEG features used in the transformation include color-coded time-frequency representations of two novel symmetry measures and a synchronization measure, based on a nearest-neighbor coherence estimate. This triplet captures three highly relevant aspects of the dynamics of the EEG background pattern, which correlate strongly with various neurologic conditions. In particular, it quantifies and visualizes the spatiotemporal distribution of the EEG power in the anterioposterior and lateral direction, and the short-distance coherence. The potential clinical use is illustrated by application of the proposed technique to various normal and abnormal EEGs, including seizure activity and the transition to sleep. The proposed transformation visualizes various essential elements of EEG background patterns. Quantitative analysis of clinical EEG recordings and transformation to alternative domains assists in the interpretation and contributes to an objective interpretation.
EEG monitoring is used routinely during the Wada test in children. We quantified EEG asymmetry us... more EEG monitoring is used routinely during the Wada test in children. We quantified EEG asymmetry using the Brain Symmetry Index (BSI) to reduce subjectivity of EEG interpretation. Clinical and procedural variables were obtained and EEG data were retrieved from 46 patients with a total of 89 injections. The BSI, the absolute value of the relative difference of the average spectral density of the right and left hemisphere, was calculated over time for all EEGs. Lateralized slowing was correctly identified in all procedures. Asymmetry was minimal at baseline (BSI 0.16) and increased with injection of amobarbital (BSI 0.49). Various patterns of the BSI were seen in distinct clinical and procedural scenarios. In this retrospective analysis, the BSI could not predict an unsuccessful Wada procedure. Our results suggest application of the BSI during the Wada test in children is feasible. Real-time calculation of the BSI during EEG monitoring in the angiography suite is warranted for further validation.► Quantification of EEG symmetry during the Wada test can reduce subjectivity of EEG interpretation. ► The Brain Symmetry Index (BSI) quantifies lateralized EEG slowing in children during the Wada test. ► Various patterns of BSI changes are associated with distinct clinical and procedural scenarios.
We apply a recently suggested measure for neural complexity (G. Tononi, O. Sporns, G.M. Edelman, ... more We apply a recently suggested measure for neural complexity (G. Tononi, O. Sporns, G.M. Edelman, Proc. Natl. Acad. Sci. 91 (1994) 5033), that is hypothesised to capture the interplay between two fundamental aspects of brain organisation, functional segregation and integration, to human EEG recordings. This measure is based on a weighted sum of entropy differences evaluated at different length scales of the system. A strong prediction is that this measure correlates with the conscious state of the subject, having lower values if consciousness is reduced (G. Tononi, G.M. Edelman, Science 282 (1998) 1846). It is found, however, that this neural complexity measure increases in neurological disorders where consciousness is severely reduced or absent. We discuss several possible explanations for this observation and suggest directions for future work.
IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society, 2013
Co-registration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a ... more Co-registration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a new, promising method for assessing cortical excitability and connectivity. Using this technique, a TMS evoked potential (TEP) can be induced and registered with the EEG. However, the TEP contains an early, short lasting artifact due to the magnetic pulse, and a second artifact, which depends on the location of stimulation and can last up to 40 ms. Different causes for this second artifact have been suggested in literature. In this study, we used principal component analysis (PCA) to suppress both the first and second artifact in TMS-EEG data. Single pulse TMS was applied at the motor and visual cortex in 18 healthy subjects. PCA using singular value decomposition was applied on single trials to suppress the artifactual components. A large artifact suppression was realized after the removal of the first five PCA components, thereby revealing early TEP peaks, with only a small suppression of later TEP components. The spatial distribution of the second artifact suggests that it is caused by electrode movement due to activation of the temporal musculature. In conclusion, we showed that PCA can be used to reduce TMS-induced artifacts in EEG, thereby revealing components of the TMS evoked potential.
Seizure : the journal of the British Epilepsy Association, 2013
The role of EEG after a first seizure has been debated. Epileptiform EEG activity is a good predi... more The role of EEG after a first seizure has been debated. Epileptiform EEG activity is a good predictor of seizure recurrence, but is reported in only 8-50% of first-seizure adult patients. Even if the EEG is abnormal, the opinions about treatment after a first seizure differ. The role of EEG in treatment decisions after remission or recurrence is also unclear. This study aims to identify neurologists&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; diagnostic strategies compared to guidelines about the use of EEG (i) after a first unprovoked generalized seizure in adults, (ii) after a recurrent seizure and (iii) in treatment decisions after recurrence or remission. All members of the Dutch Neurological Society were invited to participate in our on-line survey about the use of EEG after a first seizure, after recurrent seizures and in treatment decisions. Ten percent (N=110) of invitees participated, including mainly clinical neurophysiologists, general neurologists and neurologists-in-training. Ninety-five percent of the respondents would request a routine EEG after a first seizure. After normal MRI and EEG findings, 4% would record a second routine EEG, 48% a sleep-deprived EEG and 45% would not repeat the EEG. If a recurrent seizure occurs within six, or after 12 or 24 months, 87%, 67% and 44% would respectively conclude that the patient has epilepsy, while 57%, 65% and 72% would request an EEG. When a patient experiences a recurrence while being treated with anti-epileptic drugs, 11% of the respondents would request an EEG. Twenty-five percent would request an EEG before stopping medication after two years of remission. The variability in neurologists&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; reported strategies about the use of EEG in the diagnosis of seizures is remarkably large. Consequences for the individual patient may be significant, including treatment decisions and driving restrictions. The availability and use of more sensitive diagnostic methods may be necessary to enhance agreement between neurologists.
Epilepsy surgery depends on reliable pre-surgical markers of epileptogenic tissue. The current go... more Epilepsy surgery depends on reliable pre-surgical markers of epileptogenic tissue. The current gold standard is the seizure onset zone in ictal, i.e. chronic, electrocorticography recordings. Single pulse electrical stimulation can evoke epileptic, spike-like responses in areas of seizure onset also recorded by electrocorticography. Recently, spontaneous pathological high-frequency oscillations (80-520 Hz) have been observed in the electrocorticogram that are related to epileptic spikes, but seem more specific for epileptogenic cortex. We wanted to see whether a quantitative electroencephalography analysis using time-frequency information including the higher frequency range could be applied to evoked responses by single pulse electrical stimulation, to enhance its specificity and clinical use. Electrocorticography data were recorded at a 2048-Hz sampling rate from 13 patients. Single pulse electrical stimulation (10 stimuli, 1 ms, 8 mA, 0.2 Hz) was performed stimulating pairs of adjacent electrodes. A time-frequency analysis based on Morlet wavelet transformation was performed in a [-1 s : 1 s] time interval around the stimulus and a frequency range of 10-520 Hz. Significant (P = 0.05) changes in power spectra averaged for 10 epochs were computed, resulting in event-related spectral perturbation images. In these images, time-frequency analysis of single pulse-evoked responses, in the range of 10-80 Hz for spikes, 80-250 Hz for ripples and 250-520 Hz for fast ripples, were scored by two observers independently. Sensitivity, specificity and predictive value of time-frequency single pulse-evoked responses in the three frequency ranges were compared with seizure onset zone and post-surgical outcome. In all patients, evoked responses included spikes, ripples and fast ripples. For the seizure onset zone, the median sensitivity of time-frequency single pulse-evoked responses decreased from 100% for spikes to 67% for fast ripples and the median specificity increased from 17% for spikes to 79% for fast ripples. A median positive predictive value for the evoked responses in the seizure onset zone of 17% was found for spikes, 26% for ripples and 37% for fast ripples. Five out of seven patients with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50% of fast ripples removed by resection had a poor outcome. A wavelet transform-based time-frequency analysis of single pulse electrical stimulation reveals evoked responses in the frequency range of spikes, ripples and fast ripples. We demonstrate that time-frequency analysis of single pulse electrical stimulation can assist in delineation of the epileptogenic cortex using time-frequency single pulse-evoked fast ripples as a potential new marker.
Idiopathic childhood occipital epilepsy of Gastaut (ICOE-G) is a rare form of epilepsy, character... more Idiopathic childhood occipital epilepsy of Gastaut (ICOE-G) is a rare form of epilepsy, characterized by visual hallucinations, periods of blindness, motor seizures, and migraine‐like symptoms. A characteristic EEG feature is fixation-off sensitivity: epileptiform discharges are suppressed by visual input. Here, we present an 11-year‐old girl suffering from ICOE-G, who was studied to identify potential additional suppressors of the epileptiform discharges.
We study burst-like patterns of epileptiform discharges in non-convulsive status epilepticus (SE)... more We study burst-like patterns of epileptiform discharges in non-convulsive status epilepticus (SE).Epileptiform burst-like transients were identified by estimating the amplitude envelope of the EEG signal, and recurrence and similarities were identified by pairwise matching in the time-domain.We identified similarities in the onset of a significant fraction of the epileptiform bursts, and a bimodal distribution of the burst durations.Bursts of epileptiform discharges during a non-convulsive SE are manifestations of multiple patterns of recurring brain states.Quantitative description of ictal phenomena in epilepsy and status epilepticus adds to the knowledge of abnormal brain behavior and may assist in improved patient care.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
The author presents results from the application of a particular measure for synchronization betw... more The author presents results from the application of a particular measure for synchronization between brain areas (i.e., phase synchronization) in its behavior to detect epileptic seizure activity from scalp EEG recordings. The primary motivation for the current study was to contribute to the development of physiologic measures that both transform the EEG to a visual domain that allows a more intuitive interpretation of the interictal and ictal EEG and allows automated analysis, both relevant for real-time monitoring. EEGs from 16 patients experiencing temporal lobe and generalized seizures were analyzed. Nearest neighbor phase synchronization (NNPS) values for several frequency bands were determined. Additional analysis of the NNPS in the delta band, using different thresholds, allows construction of receiver operating characteristics (ROC) curves for each EEG analyzed. The common value for the sensitivity and the specificity, Q*, was used as a measure for the test accuracy, with values of Q* near 1.0, indicating ROC curves with sensitivity and specificity both approaching 1.0. It was found that Q* = 0.48 to 0.87, depending on the EEG analyzed, indicating that the proposed method allows seizure detection in a significant portion of the EEGs studied. Nearest neighbor phase synchronization was typically increased during seizure activity and seems to be a promising method to detect seizure activity from scalp EEG recordings. The proposed visualization allows an intuitive interpretation of the EEG and may assist in real-time monitoring.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 2010
Purpose Tilt table testing mainly evaluates the systemic cardiovascular part of the autonomic ner... more Purpose Tilt table testing mainly evaluates the systemic cardiovascular part of the autonomic nervous system, while it is assumed that the finger wrinkling test assesses the peripheral part of the autonomic nervous system. In this study we explored whether the finger wrinkling test could be a useful test for autonomic dysfunction and whether the clinical evaluation of wrinkling can be improved by digital analysis of photographs. Methods As much as 20 healthy subjects and 15 patients underwent tilt table testing and finger wrinkling testing. During the finger wrinkling test the right hand was immersed in water at 40°C. The degree of wrinkling was assessed with a 5-point clinical scale at baseline, 5, 15 and 30 min of immersion. Photographs were taken at the same intervals. Several features were evaluated using digital analysis: length and gradient of automatically detected wrinkle and mean, maximum, minimum, variance and derivative of grey value of pixels. Results Clinical scoring of wrinkling allowed differentiation between healthy subjects and patients with a normal and an abnormal response to tilt table testing. Relevant features obtained with digital analysis were mean grey value and the gradient of automatically detected wrinkle. McNemar’s test showed no difference in test results between the tilt table test and the finger wrinkling test with a kappa of 0.68. Conclusion The finger wrinkling test can be used as a screening test before tilt table testing. Visual evaluation of wrinkling is still superior to digital analysis of photographs.
The activity of the brain during observation or imagination of movements might facilitate the rel... more The activity of the brain during observation or imagination of movements might facilitate the relearning of motor functions after stroke. The present study examines whether there is an additional effect of imagination over observation-only. Eight healthy subjects observed and observed-and-imagined a movement of a hand; 64-channel EEG was used to measure brain activity. The synchronization of the theta (4–8 Hz), alpha (8–13 Hz) and beta (13–25 Hz) frequency bands was calculated and plotted in topoplots. The temporal changes of the sensorimotor area (C3, C4) and the centro-parietal cortex (Pz) were analyzed in the two experimental conditions. During observation-and-imagination, a significant larger desynchronization (p = 0.004) in the sensorimotor area was found compared to observation-only in all electrodes and frequency bands. In addition, temporal differences were found between observation and observation-and-imagination in the alpha frequency bands. During observation-and-imagination, modulations of EEG rhythms were stronger than during observation-only in the theta, alpha and beta frequency bands and during almost the whole activity fragment. These findings suggest an additive effect of imagination to observation in the rehabilitation after stroke.
The applicability of corticomuscular coherence (CMC) as a connectivity measure is limited since o... more The applicability of corticomuscular coherence (CMC) as a connectivity measure is limited since only 40–50 % of the healthy population presents significant CMC. In this study, we applied continuous joint position perturbations to obtain a more reliable measure of connectivity in motor control. We evaluated the coherence between joint position perturbations and EEG (position-cortical coherence, PCC) and CMC. Healthy subjects performed two isotonic force tasks against the handle of a wrist manipulator. The baseline task was isometric; in the perturbed task, the handle moved continuously with small amplitude. The position perturbation signal covered frequencies between 5 and 29 Hz. In the perturbed task, all subjects had significant PCC and 86 % of the subjects had significant CMC, on both stimulus and non-stimulus frequencies. In the baseline task, CMC was present in only 45 % of the subjects, mostly on beta-band frequencies. The position perturbations during an isotonic force task elicited PCC in all subjects and elicited CMC in most subjects on both stimulus and non-stimulus frequencies. Perturbed CMC possibly arises by two separate processes: an intrinsic process, similar to the process in an unperturbed task, involving both efferent and afferent pathways; and a process related to the excitation of the afferent and efferent pathways by the perturbation. These processes cannot be separated. PCC, however, reflects connectivity via the afferent pathways only. As PCC was present in all healthy subjects, we propose this coherence as a reliable measure for connectivity in motor control via the afferent pathways.
Although a large number of studies have been devoted to establishing correlations between changes... more Although a large number of studies have been devoted to establishing correlations between changes in amplitude and frequency of EEG alpha oscillations and cognitive processes, it is currently unclear through which physiological mechanisms such changes are brought about. In this study we use a biophysical model of EEG generation to gain a fundamental understanding of the functional changes within the thalamo-cortical system that might underly such alpha responses. The main result of this study is that, although the physiology of the thalamo-cortical system is characterized by a large number of parameters, alpha responses effectively depend on only three variables. Physiologically, these variables determine the resonance properties of feedforward, cortico-thalamo-cortical, and intra-cortical circuits. By examining the effect of modulations of these resonances on the amplitude and frequency of EEG alpha oscillations, it is established that the model can reproduce the variety of experimentally observed alpha responses, as well as the experimental finding that changes in alpha amplitude are typically an order of magnitude larger than changes in alpha frequency. The modeling results are also in line with the fact that alpha responses often correlate linearly with indices characterizing cognitive processes. By investigating the effect of synaptic and intrinsic neuronal parameters, we find that alpha responses reflect changes in cortical activation, which is consistent with the hypothesis that alpha activity serves to selectively inhibit cortical regions during cognitive processing demands. As an example of how these analyses can be applied to specific experimental protocols, we reproduce benzodiazepine-induced alpha responses and clarify the putative underlying thalamo-cortical mechanisms. The findings reported in this study provide a fundamental physiological framework within which alpha responses observed in specific experimental protocols can be understood.► Alpha responses are determined by three thalamo-cortical subcircuits. ► Alpha responses reflect changes in the level of cortical activation. ► Physiological explanation of benzodiazepine-induced alpha responses responses.
During the maintenance period of propofol-induced general anesthesia, specific changes in spontan... more During the maintenance period of propofol-induced general anesthesia, specific changes in spontaneous EEG rhythms can be observed. These comprise increased delta and theta power and the emergence of alpha oscillations over frontal regions. In this study we use a meanfield model of the thalamo-cortical system to reproduce these changes and to elucidate the underlying mechanisms. The model is able to reproduce the most dominant changes in the EEG and suggests that they are caused by the amplification of resonances within the thalamo-cortical system. Specifically, while observed increases in delta and alpha power are reflections of amplified resonances in the respective frequency bands, increases in theta power are caused indirectly by spectral power leakage from delta and alpha bands. The model suggests that these changes are brought about through increased inhibition within local cortical interneuron circuits. These results are encouraging and motivate more extensive use of neural meanfield models in elucidating the physiological mechanisms underlying the effects of pharmacological agents on macroscopic brain dynamics.► The mechanisms underlying changes in EEG rhythms during propofol-induced general anesthesia are incompletely understood at present. ► Meanfield modeling of the thalamo-cortical system provides an integrated explanation. ► Modeling suggests that the EEG changes are caused by amplification of thalamo-cortical resonances. ► Local inhibitory circuits in cortical tissue play an essential role.
Under nonideal voltage-clamp conditions, unitary currents in the cell-attached patch (CAP) config... more Under nonideal voltage-clamp conditions, unitary currents in the cell-attached patch (CAP) configuration of the patch-clamp technique are decaying instead of rectangular. From these data, four parameters can be determined when multiple identical channels are present. We analyzed an electrical equivalent circuit of the CAP configuration. This analysis yielded, for single-channel resistance, attached-cell membrane resistance, patch resistance, and attached-cell membrane capacitance, a set of different equations to calculate their values from these four parameters. To choose the most robust equation, those that yielded the same resistor/capacitance were compared on the basis of their sensitivity for inevitable deviations of the parameters from their nominal values. The results of our theoretical study are of methodological interest: 1) because they confirm that, under special conditions, CAP measurements can be used to measure electrical membrane properties of intact cells (this is important inasmuch as the CAP is the only configuration in which the cytoplasm of cells remains undisturbed) and 2) because we identify the level of voltage clamp and the equations with which the electrical properties can be determined with optimal accuracy.
Data on quetiapine overdosage are only sparsely available in the literature. This study provides ... more Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.
Three neonates had diverse kinds of central apnoea. The first child, a girl aged 3 weeks, had an ... more Three neonates had diverse kinds of central apnoea. The first child, a girl aged 3 weeks, had an upper respiratory tract infection caused by the respiratory syncytial virus; she was intubated and needed ventilatory support for three days. The second patient, a boy of 17 days, had an Arnold-Chiari-malformation with apnoeas treated with a carbonic anhydrase inhibitor (acetazolamide). The third patient, a boy of 5 days, had central apnoeas of epileptic origin and was treated with phenobarbital. All three recovered well. If in an infant with apnoeas no paediatric explanation is found, and the child is neurologically at risk, it is advisable to make an EEG to determine if an epileptic substrate is present, even in the absence of motor phenomena.
This European funded research project aims for the development of a portable pocket sized electro... more This European funded research project aims for the development of a portable pocket sized electronic multiple-sensor micro-system for low cost, high volume and high cost, low volume equipment for improved diagnosis of pulmonary diseases and pulmonary diagnostic functions in general. The microsystem will measure Peak Expiratory flow (PEF), Temperature (T), Pressure (P) and Relative Humidity (RH) and will comply with (1) the Body Temperature Pressure Saturation standard (BTPS), (2) The American Thoracic Society, ATS and (3) the Recommendations of the European Respiratory Society, ERS. A single chip multiple-sensor has been realized applying Silicon and MEMS technology. P-type doped resistive elements are used for the sensing elements, which guarantees best reproducibility and accuracy. Much attention has been devoted to the right mounting technique where response time is a main issue here in particular for the PEF measurements. So far, except for the RH measurement all elements are integrated on one single chip
IEEE transactions on bio-medical engineering, 1997
The authors describe a solid-state, silicon integrated, bidirectional flow sensor for respiratory... more The authors describe a solid-state, silicon integrated, bidirectional flow sensor for respiratory applications. The sensor is a thermal vector sensor. The electronic circuitry for obtaining bidirectional sensitivity is presented together with actual application to a healthy volunteer put on mechanical ventilation. The sensor's input flow range is from -60 to +60 L/min, and its rise-time is ≤40 ms and fall-time is ≤60 ms. The effect of changes in gas composition as used in mechanically ventilated patients on the sensor output signal are estimated to be less than 2%. The temperature sensitivity is about -1.5% per degree Celsius.
We present a novel method to eliminate additive drift in silicon thermal flow sensors, the Altern... more We present a novel method to eliminate additive drift in silicon thermal flow sensors, the Alternating Direction method(ADM). In this sensor design the flow signal is contained in the gradient of a two-dimensional temperature distribution T(x,y) on the chip. This temperature gradient is induced by the convective heat transfer of the flowing medium, which is overall dependent on (i) the physical aspects of the flowing medium, (ii) the physical characteristics of the sensor and (iii) the thermal coupling of the sensor to its holder and environment. Ideally, the gradient in T(x,y) is a homogeneous function of (i). In real-world applications, however, the non-ideal aspects (uncertainty in the functional relationship of T(x,y) on the flow) are generally due to asymmetries in the silicon chip and its mounting, resulting in a further additive dependency of the gradient T(x,y) on (ii)-(iii). With thermal flow measurement of very low airflow velocities (0-30 cm/s), the factors (ii) and (iii) can have dramatic influence on the thermal gradient, for instance by inducing flow disturbances by the thermally induced convection. These additive dependencies contribute to unacceptable measurement errors in the low flow regime. ADM applies to vector sensors, having anisotropic sensitivity for the measurand S, and isotropic sensitivity for all other possible input signals, such as those induced by the above mentioned influences (ii) and (iii). ADM eliminates virtually all drift, providing the desired performance enhancement especially for the purpose of long term volume measurements. In this paper, the theory and possible applications of ADM are presented
ObjectiveDeep learning methods have shown potential in automating interictal epileptiform dischar... more ObjectiveDeep learning methods have shown potential in automating interictal epileptiform discharge (IED) detection in electroencephalograms (EEGs). While it is known that these algorithms are dependent on the type of data used for training, this has not been explored in EEG analysis applications. We study the difference in performance of deep learning algorithms on routine and ambulatory EEG data.MethodsWe trained the same neural network on three datasets: 166 routine EEGs (VGGC–R), 75 ambulatory EEGs (VGGC–A) and a combination of the two data types (VGGC-C, 241 EEGs total). Networks were tested on 34 routine EEGs and 33 ambulatory recordings, where all 2 s non-overlapping epochs were labeled with a probability that expressed the likelihood of containing an epileptiform discharge. Performance was quantified as sensitivity, specificity and the rate of false detections (FPR).ResultsThe VGGC-R led to 84% sensitivity at 99% specificity on the routine EEGs, but its sensitivity was only ...
RATIONALE: Vagus nerve stimulation (VNS) is a treatment option in the case of refractory epilepsy... more RATIONALE: Vagus nerve stimulation (VNS) is a treatment option in the case of refractory epilepsy. However, several side effects have been reported, including dyspnea, coughing and bradycardias [JCA 2010: 22;213-222]. Although some patients experience hardly any side effects from the stimulation during rest, they mention a decrease in physical condition during exercise is. The experience of a decrease in physical condition during exercise is reported as shortness of breath when the stimulator is on. It is unclear whether this actually has a laryngeal or respiratory cause, or whether there are cardiac or combined causes as well. The aim of this study is to explore the contribution of these various potential causes to the exercise intolerance reported by several patients treated with a VNS device. METHODS: In a case controlled observational study, 5 epilepsy patients who report side effects during exercise are compared to 5 patients without side effects and 5 healthy subjects. All sub...
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Stroke/Ischaemia/Spreading Depression by Michel J.A.M. van Putten
Objective: In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This
predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.
Methods: We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials
(CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs
and CMAPs.
Results: Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean 6 standard deviation 3065 vs. 4666
minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in
strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all
more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent
Na+ conductance during continuing depolarisation.
Interpretation: Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with
faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster
depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be
attributed to differences in ion channel composition between sensory and motor axons.
Received October 31, 2012.
Revision received January 30, 2013.
Accepted February 6, 2013.
Copyright © 2013 the authors 0270-6474/13/335915-09$15.00/0
Objective: In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This
predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.
Methods: We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials
(CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs
and CMAPs.
Results: Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean 6 standard deviation 3065 vs. 4666
minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in
strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all
more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent
Na+ conductance during continuing depolarisation.
Interpretation: Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with
faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster
depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be
attributed to differences in ion channel composition between sensory and motor axons.
Received October 31, 2012.
Revision received January 30, 2013.
Accepted February 6, 2013.
Copyright © 2013 the authors 0270-6474/13/335915-09$15.00/0