Jan-Willem Elting

Comparison of serum S-100 protein levels following stroke and traumatic brain injury

Temporal changes in serum S-100 protein levels were compared between patients with ischemic stroke, transient ischemic attack (TIA) and traumatic brain injury (TBI). In addition, S-100 levels were correlated with clinical severity and outcome. Measurements were done with a LIA-mat((R)) Sangtec((R)) 100 using an automated immunoluminometric assay. Serum S-100 was measured in 21 stroke patients, 18 TIA patients and ten TBI patients on days 1 (0-24 h), 2, 3, 4, 5 or 6 and 8 or 9. In a control group of 28 healthy volunteers one measurement was done. For the stroke and TIA patients, National Institutes of Health Stroke Scale (NIHSS) scores were obtained on admission and on day 10. For the TBI patients, Glasgow Coma Scale (GCS) scores were obtained on admission and Glasgow Outcome Scale (GOS) scores were obtained after 6 months. Changes in serum S-100 levels over the first 3 days were significantly different between stroke and TBI patients (P=0.014) and between stroke and TIA patients (P=0.006). Peak concentrations of S-100 were most often observed on day 3 or 4 after stroke and on day 1 or 2 after TBI. In the stroke patients individual S-100 peak levels correlated well with the NIHSS score on admission (r=0.58 P=0.014) and the change in NIHSS score between day 10 and day 1 (r=0.65, P=0. 005). In the TBI patients a good correlation between individual peak levels of S-100 and the GCS score on admission (r=-0.81, P=0.010) and the GOS score 6 months after the trauma was found (r=-0.87, P=0. 004). We conclude that there is a significant difference in temporal changes of S-100 levels between ischemic stroke and TBI patients. This suggests different pathophysiological mechanisms. The results of this study further confirm that peak levels of serum S-100 correlate with neurological deficit resulting from either stroke or TBI.

Sympathetic regulation of cerebral blood flow in humans: a review

Cerebral blood flow (CBF) is regulated by vasomotor, chemical, metabolic, and neurogenic mechanisms. Even though the innervation of cerebral arteries is quite extensively described and reviewed in the literature, its role in regulation of CBF in humans remains controversial. We believe that insufficient attention has so far been focused on the potential role of the innervation of the cerebral vasculature in cerebral autoregulation in humans. We have performed an extensive search and selection of available literature on electrical, chemical, and surgical manipulations of the sympathetic innervation of cerebral arteries, and the effects of circulation sympathetically active agents on CBF. Studies on (surgical) ganglion block show a role of sympathetic tone in preventing increases in CBF in humans, which are consistent with the view based on animal studies. Both direct innervation of the cerebral arteries from cervical ganglia and stimulation of adrenergic receptors by circulating sympathomimetics prevent sudden increases of CBF associated with hypertension and hypercapnia. We postulate that under normal physiological conditions neurogenic control has little influence on cerebral autoregulation as other methods of control (vasomotor, chemical, and metabolic) are dominant. In severely challenging circumstances, such as delayed cerebral ischaemia after subarachnoid haemorrhage, these methods might be overwhelmed, increasing the relative importance of neurogenic, sympathetic control of CBF. This insight might lead to future therapeutic possibilities.

AMPA Antagonist ZK200775 in Patients With Acute Ischemic Stroke

Background and Purpose— S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with the &agr;-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients. Methods— In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS). Results— In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons. Conclusions— The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.

P300 after head injury: Pseudodelay caused by reduced P3A amplitude

OBJECTIVE We compared conventional P300 analysis with source analysis in normal subjects and head-injury patients. Based on earlier findings of improved P300 component identification and reduced P3B latency variability with source analysis in normal subjects, our aim was to investigate whether source analysis could improve the distinction between these groups. METHODS In total, 21 healthy control subjects and 21 patients with mild to moderate head injury were included in this study. A standard auditory 2-tone oddball paradigm was used. Latencies and amplitudes obtained with conventional P300 analysis were compared with source analysis results. RESULTS With conventional analysis, head-injury patients had delayed P300 latencies and reduced P300 amplitudes in comparison to controls, while source analysis showed no latency differences for both P3A and P3B components. Instead, source analysis indicated absence of P3A components in 43% of patients. CONCLUSIONS The P300 delay in head-injury patients, observed with conventional analysis, is a pseudodelay caused by decreased P3A amplitudes. Consequently, the unaffected P3B component with its later latency determines conventional P300 latency in these patients. SIGNIFICANCE Conventional P300 latency cannot be used to conclude that there was delayed early stimulus processing in head-injury patients.

Dynamics of cerebral blood flow in patients with mild non-ischaemic heart failure.

Heart failure (HF) is associated with tissue hypoperfusion and congestion leading to organ dysfunction. Although cerebral blood flow (CBF) is preserved over a wide range of perfusion pressures in healthy subjects, it is impaired in end‐stage HF. We aimed to compare CBF, autoregulation, and cognitive function in patients with mild non‐ischaemic HF with healthy controls.

Intra-arterial blood pressure reading in intensive care unit patients in the lateral position

BACKGROUND Routine lateral turning of patients has become an accepted standard of care to prevent complications of immobility. The haemodynamic and oxygenation effects for patients in both lateral positions (45°) are still a matter of debate. We aimed to study the effect of these positions on blood pressure, heart rate and oxygenation in a general intensive care population. DESIGN Observational study. METHOD Twenty stable intensive care unit patients had intra-arterial blood pressure recordings in the supine and lateral positions with the correction of hydrostatic height compared with a fixed reference point (phlebostatic level). A multilevel model was used to analyse the data. RESULTS Mean arterial pressure readings in the lateral positions were, on average, 5 mmHg higher than in the supine position (p < 0.001). There were no significant differences between mean arterial pressure recordings in the left and right lateral position (p = 1.0). No important differences in oxygenation and heart rate were observed. After correction for covariates, the effects persisted. CONCLUSION Our study demonstrated an increase, albeit small, in blood pressure in the lateral positions. No major differences between the left and right lateral position were found. No important differences in oxygenation and heart rate were observed. RELEVANCE TO CLINICAL PRACTICE Turning haemodynamically stable patients in the intensive care unit has no important effects on blood pressure measurements when continuous hydrostatic height correction is applied.

Electrical modulation of the sympathetic nervous system in order to augment cerebral blood flow: a protocol for an experimental study

Introduction Cerebral blood flow (CBF) is regulated by several mechanisms. Neurogenic control has been a matter of debate, even though several publications reported the effects of changes in sympathetic tone on CBF. Transcutaneous electrical nerve stimulation and spinal-cord stimulation have been shown to influence peripheral and cerebral blood flow through a sympathetic pathway. The authors hypothesise that certain pathological conditions result in a relative increase in the neurogenic regulation of CBF and that this regulation can be modulated electrically. Methods and analysis Patients with cerebral vasospasm after subarachnoid haemorrhage will be included. The experimental set-up measures several parameters that are involved in cerebral blood flow regulation in patients with cerebral vasospasm after subarachnoid haemorrhage. Measurements are taken at baseline and with stimulation in several frequencies. An ad hoc statistical analysis is used to evaluate different settings of the electrical stimulation. Autoregulation is evaluated with transfer function analysis and autoregulatory index calculations. Ethics and dissemination Ethical registration was granted by Medical Review Ethics Committee Groningen (ID METc 2010.123). All participants provide written informed consent on participation. Upon finishing a pilot study to investigate feasibility and effect, either future prospective (randomised) studies will be designed, or other modalities of electrical stimulation will be explored using the same set-up. Trial Registration Dutch Trial Registry: NTR2358.

The Inter-rater Variability of Clinical Assessment in Post-anoxic Myoclonus

Background Acute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group that could support prognostication in post-anoxic encephalopathy; however, the inter-rater variability of clinically assessing these PAM subtypes is unknown. Methods We prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity Scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)). Results Poor inter-rater agreement was found for phenotype and stimulus sensitivity (κ=−0.05), moderate agreement for localization (κ=0.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC)=0.64) and almost perfect agreement for the UMRS (ICC=0.82). Discussion Clinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable; however, the relation between PAM severity and outcome is unknown.

Wavelet coherence analysis: a new approach to distinguish organic and functional tremor types

OBJECTIVE To distinguish tremor subtypes using wavelet coherence analysis (WCA). WCA enables to detect variations in coherence and phase difference between two signals over time and might be especially useful in distinguishing functional from organic tremor. METHODS In this pilot study, polymyography recordings were studied retrospectively of 26 Parkinsonian (PT), 26 functional (FT), 26 essential (ET), and 20 enhanced physiological (EPT) tremor patients. Per patient one segment of 20 s in duration, in which tremor was present continuously in the same posture, was selected. We studied several coherence and phase related parameters, and analysed all possible muscle combinations of the flexor and extensor muscles of the upper and fore arm. The area under the receiver operating characteristic curve (AUC-ROC) was applied to compare WCA and standard coherence analysis to distinguish tremor subtypes. RESULTS The percentage of time with significant coherence (PTSC) and the number of periods without significant coherence (NOV) proved the most discriminative parameters. FT could be discriminated from organic (PT, ET, EPT) tremor by high NOV (31.88 vs 21.58, 23.12 and 10.20 respectively) with an AUC-ROC of 0.809, while standard coherence analysis resulted in an AUC-ROC of 0.552. CONCLUSIONS EMG-EMG WCA analysis might provide additional variables to distinguish functional from organic tremor. SIGNIFICANCE WCA might prove to be of additional value to discriminate between tremor types.

The interrelation between clinical presentation and neurophysiology of posthypoxic myoclonus

Posthypoxic myoclonus (PHM) in the first few days after resuscitation can be divided clinically into generalized and focal (uni‐ and multifocal) subtypes. The former is associated with a subcortical origin and poor prognosis in patients with postanoxic encephalopathy (PAE), and the latter with a cortical origin and better prognosis. However, use of PHM as prognosticator in PAE is hampered by the modest objectivity in its clinical assessment. Therefore, we aimed to obtain the anatomical origin of PHM with use of neurophysiological investigations, and relate these to its clinical presentation.