Electroencephalographic Findings in Posthypoxic Myoclonus.

The physical examination findings of early posthypoxic myoclonus (PHM) are associated with poor prognosis. Recent findings indicate that patients with multifocal PHM, assumed to have a cortical origin, have a comparable outcome to resuscitated patients without PHM. Generalized PHM, assumed to have a subcortical myoclonus origin, is still associated with a bad clinical outcome. It is not known whether the electroencephalographic (EEG) findings differ between the multifocal and generalized myoclonus groups nor is the clinical significance clearly defined. Forty-three patients with PHM were retrospectively derived from an EEG database. Patients were categorized as having multifocal (i), generalized (ii), or undetermined (iii) PHM. Outcome was expressed in cerebral performance category scores. The EEG background was categorized into isoelectric (I), low voltage (II), burst suppression (III), status epilepticus (SE; IV), diffuse slowing (V), and mild encephalopathic or normal (VI). 17 patients had generalized PHM and 23 had multifocal PHM (3 undetermined). The EEG showed more SE in generalized compared to multifocal PHM (64% vs 13%, P< .001). Diffuse slowing was more often present in multifocal PHM (52% vs 17%, P < .05). Early-onset myoclonus occurred significantly more often in generalized PHM, and early generalized PHM was invariantly associated with poor outcome. In conclusion, patients with generalized PHM showed more SE. These EEG findings might be either subcortical corollaries or primarily cortical phenomena. Our retrospective results conflict with currently used clinical criteria for myoclonus classification, and we suggest that more refined difference may be needed for accurate assessment of PHM. To better understand PHM, prospective research with standardized clinical assessment and quantitative EEG analysis is needed.

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.

Inter-muscular coherence in speed skaters with skater's cramp.

INTRODUCTION: Skater's cramp is a career-ending movement disorder in expert speed skaters noted to be a likely task-specific dystonia. In other movement disorders, including task-specific dystonia, studies have found evidence of central dysregulation expressed as higher inter-muscular coherence. We looked at whether inter-muscular coherence was higher in affected skaters as a possible indicator that it is centrally driven, and by extension further evidence it is a task-specific dystonia. METHODS: In 14 affected and 14 control skaters we calculated inter-muscular coherence in the theta-band in a stationary task where tonic muscle activation was measured at 10%, 20% and 50% of maximum voluntary contraction. Additionally, we calculated wavelet coherence while skating at key moments in the stroke cycle. RESULTS: Coherence did not differ in the stationary activation task. While skating, coherence was higher in the impacted leg of affected skaters compared to their non-impacted leg, p = .05, η2 = 0.031, and amplitude of electromyography correlated with coherence in the impacted leg, p = .009, R2adjusted = 0.41. A sub-group of severely affected skaters (n = 6) had higher coherence in the impacted leg compared to the left and right leg of controls, p = .02, Cohen's d = 1.59 and p = .01, Cohen's d = 1.63 respectively. Results were less clear across the entire affected cohort probably due to a diverse case-mix. CONCLUSION: Our results of higher coherence in certain severe cases of skater's cramp is preliminary evidence of a central dysregulation, making the likelihood it is a task-specific dystonia higher.

Intermuscular coherence as a biomarker of subthalamic nucleus deep brain stimulation efficacy in Parkinson's disease.

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD. METHODS: EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated. RESULTS: Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01). CONCLUSIONS: Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement. SIGNIFICANCE: We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS.

The diagnostic value of clinical neurophysiology in hyperkinetic movement disorders: A systematic review.

INTRODUCTION: To guide the neurologist and neurophysiologist with interpretation and implementation of clinical neurophysiological examinations, we aim to provide a systematic review on evidence of electrophysiological features used to differentiate between hyperkinetic movement disorders. METHODS: A PRISMA systematic search and QUADAS quality evaluation has been performed in PubMed to identify diagnostic test accuracy studies comparing electromyography and accelerometer features. We included papers focusing on tremor, dystonia, myoclonus, chorea, tics and ataxia and their functional variant. The features were grouped as 1) basic features (e.g., amplitude, frequency), 2) the influence of tasks on basic features (e.g., entrainment, distraction), 3) advanced analyses of multiple signals, 4) and diagnostic tools combining features. RESULTS: Thirty-eight cross-sectional articles were included discussing tremor (n = 28), myoclonus (n = 5), dystonia (n = 5) and tics (n = 1). Fifteen were rated as 'high quality'. In tremor, the basic and task-related features showed great overlap between clinical tremor syndromes, apart from rubral and enhanced physiological tremor. Advanced signal analyses were best suited for essential, parkinsonian and functional tremor, and cortical, non-cortical and functional jerks. Combinations of electrodiagnostic features could identify essential, enhanced physiological and functional tremor. CONCLUSION: Studies into the diagnostic accuracy of electrophysiological examinations to differentiate between hyperkinetic movement disorders have predominantly been focused on clinical tremor syndromes. No single feature can differentiate between them all; however, a combination of analyses might improve diagnostic accuracy.

Two cases with postural axial tremor: Consider a genetic origin.

We present two cases with postural axial tremor predominantly involving the head, trunk, and shoulders. In the first patient, the postural tremor occurred in multiple attacks a day lasting approximately 10 min. The second patient developed a progressive tremor of his head and arms, worsened during sitting and standing. Electrophysiological supported the postural axial tremor in both patients with a varying 3-10 Hz tremor frequency between different muscles and within the same muscles at different times. Postural axial tremor is a rare and complex movement disorder. The majority of cases are caused by acquired cerebellar pathology. However, isolated cases with underlying genetic disorders are described in literature. Here, we illustrate how to differentiate paroxysmal axial tremor from other axial hyperkinetic movement disorders and extend the genetic heterogeneity of this intriguing movement disorder phenotype.

Tremor and myoclonus.

Tremor and myoclonus are two common hyperkinetic movement disorders. Tremor is characterized by rhythmic oscillatory movements while myoclonic jerks are usually arrhythmic. Tremor can be classified into subtypes including the most common types: essential, enhanced physiological, and parkinsonian tremor. Myoclonus classification is based on its anatomic origin: cortical, subcortical, spinal, and peripheral myoclonus. The clinical presentations are unfortunately not always classic and electrophysiologic investigations can be helpful in making a phenotypic diagnosis. Video-polymyography is the main technique to (sub)classify the involuntary movements. In myoclonus, advanced electrophysiologic testing, such as back-averaging, coherence analysis, somatosensory-evoked potentials, and the C-reflex can be of additional value. Recent developments in tremor point toward a role for intermuscular coherence analysis to differentiate between tremor subtypes. Classification of the movement disorder based on clinical and electrophysiologic features is important, as it enables the search for an etiological diagnosis and guides tailored treatment.

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia.

OBJECTIVE: Finding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients. METHODS: EEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4-12 Hz) and beta band (13-30 Hz) peak coherences were studied. RESULTS: Dystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3-10), TWSTRS: 22%, median 6.8 (IQR 4-9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit. CONCLUSIONS: Peak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity. SIGNIFICANCE: IMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.

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.

Improving neurophysiological biomarkers for functional myoclonic movements.

INTRODUCTION: Differentiating between functional jerks (FJ) and organic myoclonus can be challenging. At present, the only advanced diagnostic biomarker to support FJ is the Bereitschaftspotential (BP). However, its sensitivity is limited and its evaluation subjective. Recently, event related desynchronisation in the broad beta range (13-45 Hz) prior to functional generalised axial (propriospinal) myoclonus was reported as a possible complementary diagnostic marker for FJ. Here we study the value of ERD together with a quantified BP in clinical practice. METHODS: Twenty-nine patients with FJ and 16 patients with cortical myoclonus (CM) were included. Jerk-locked back-averaging for determination of the 'classical' and quantified BP, and time-frequency decomposition for the event related desynchronisation (ERD) were performed. Diagnostic gain, sensitivity and specificity were obtained for individual and combined techniques. RESULTS: We detected a classical BP in 14/29, a quantitative BP in 15/29 and an ERD in 18/29 patients. At group level we demonstrate that ERD in the broad beta band preceding a jerk has significantly higher amplitude in FJ compared to CM (respectively -0.14 ± 0.13 and +0.04 ± 0.09 (p < 0.001)). Adding ERD to the classical BP achieved an additional diagnostic gain of 53%. Furthermore, when combining ERD with quantified and classical BP, an additional diagnostic gain of 71% was achieved without loss of specificity. CONCLUSION: Based on the current findings we propose to the use of combined beta ERD assessment and quantitative BP analyses in patients with a clinical suspicion for all types of FJ with a negative classical BP.

Myoclonus subtypes in tertiary referral center. Cortical myoclonus and functional jerks are common.

OBJECTIVE: To evaluate the accuracy of clinical phenotyping of myoclonus patients and to determine differentiating clinical characteristics between cortical (CM), subcortical (SCM), spinal (SM), peripheral (PM) myoclonus, and functional jerks (FJ). METHODS: Clinical notes for all patients with myoclonus over an 8-year period (2006-2014) were reviewed retrospectively. We used the conclusion of electrophysiological testing as definite diagnosis of myoclonus or FJ. RESULTS: 85 patients were identified suffering from CM (34%), SCM (11%), SM (6%), PM (2%), and 47% FJ. The clinical diagnosis of myoclonus was confirmed by electrophysiological testing in 74% and its subtype in 78% of cases. CM was characterized by an early age of onset, facial myoclonus, and provocation by action. Differentiating features of FJ were an abrupt onset, preceding contributing events and provocation by a supine position. CONCLUSION: The majority of clinical myoclonic jerk cases were functional in our heterogeneous tertiary clinic cohort. CM was the main anatomical myoclonic subtype. Clinical diagnosis was accurate in the majority of cases, although electrophysiological testing was important to verify the clinical classification. SIGNIFICANCE: In patients with jerky movements a functional diagnosis should be considered. Determination of the myoclonic subtypes is important to initiate tailored treatment.

How typical are 'typical' tremor characteristics? Sensitivity and specificity of five tremor phenomena.

INTRODUCTION: Distinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five 'typical' tremor phenomena. METHODS: Retrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on 'typical' characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (FT)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the 'typical' group was compared to the whole group. RESULTS: Most patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FT, whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity. CONCLUSION: In this study, we retrospectively determined sensitivity and specificity for five 'typical' tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders.

Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus. METHODS: Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed. RESULTS: A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities. CONCLUSIONS: Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.

Usefulness of intermuscular coherence and cumulant analysis in the diagnosis of postural tremor.

OBJECTIVE: To investigate the potential value of two advanced EMG measures as additional diagnostic measures in the polymyographic assessment of postural upper-limb tremor. METHODS: We investigated coherence as a measure of dependency between two EMG signals, and cumulant analysis to reveal patterns of synchronicity in EMG activity in muscle pairs. Eighty datasets were analyzed retrospectively, obtained from four groups: essential tremor (ET), Parkinson's disease (PD), enhanced physiological tremor (EPT), and functional tremor (FT). RESULTS: Intermuscular coherence was highest in the PD group (0.58), intermediate in FT (0.43) and ET (0.40), and weakest in EPT (0.16) (p=0.002). EPT patients could be distinguished by low coherence: coherence <0.18 in the wrist+elbow extensors differentiates EPT in this sample with a sensitivity of 86% and specificity of 84%. Cumulant analysis showed predominantly alternating activity between wrist and elbow extensor in ET patients, while a more synchronous pattern was predominant in PD, EPT and FT (p=0.008). EMG activity in wrist and elbow flexors tended to be more synchronous in PD (p=0.059). CONCLUSION: Our results suggest that coherence and cumulant analysis may be of additional value in the diagnostic work-up of postural tremor. SIGNIFICANCE: These additional measures may be helpful in diagnosing difficult tremor cases.

Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke.

A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a cerebral hemispheric stroke between 12 and 24 h after stroke onset. In cortical ischemic strokes complicated by hyperglycemia (blood glucose concentration > 7 mmol/l) we found significantly higher NSE levels than in normoglycemic patients. In lacunar ischemic strokes NSE levels were not significantly different between normoglycemic and hyperglycemic patients. Our findings support the concept that hyperglycemia during acute cortical ischemic stroke is associated with enhanced neuronal cell death.

Continuous pulse oximetry in acute hemiparetic stroke.

BACKGROUND AND PURPOSE: Hypoxemia can adversely affect ischemic brain tissue in laboratory animals. The aim of this study was to assess the value of early continuous monitoring with pulse oximetry in detecting arterial oxygen desaturations in patients with acute hemiparetic stroke, and the effects of oxygen administration. METHODS: Over a period of 6 months 49 consecutive patients with acute hemiparetic stroke of

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.

P300 component identification using source analysis techniques: reduced latency variability.

P300 latency variability in normal subjects is a complicating factor in clinical event-related potential studies because it limits diagnostic applicability. The current study was conducted to determine whether identification of P300 (P3A and P3B) components using source analysis techniques can reduce variability in P300 parameters. Data were recorded with a 128-channel EEG system in 18 healthy subjects. The authors used a standard, auditory two-tone oddball paradigm with targets of 2000 Hz and standards of 1000 Hz. Two simple source analysis models with one or two rotating dipoles were applied to grand average data and individual data. Dipole time courses were combined with mapping results to extract P3A and P3B component latencies. Latencies obtained with conventional P300 analysis were compared with source analysis results. The source analysis method identified both P3A and P3B components in a substantially larger percentage of subjects (88% vs. 33%) than the conventional method. The source analysis method yielded a later mean P3B latency (357 msec vs. 323 msec, P < 0,001) with a smaller standard deviation (9 msec vs. 23 msec, P = 0,003) than the conventional P300 method. The relative contribution of the temporally separate P3A and P3B components to the P300 complex amplitude is highly variable. This explains the larger latency standard deviation in conventional P300 analysis. The source analysis method was able to identify P300 components in a large percentage of the cases. The result is a considerable reduction of P300 latency variability in normal subjects. This could have important consequences for clinical event-related potential research, because diagnostic sensitivity and specificity of P300 latency may improve with this method.

Predicting outcome from coma: man-in-the-barrel syndrome as potential pitfall.

The Glasgow coma scale motor score is often used in predicting outcome after hypoxic-ischemic coma. Judicious care should be exerted when using this variable in predicting outcome in patients with coma following hypotension since borderzone infarction can obscure the clinical picture. We describe a patient who underwent skull base surgery for a schwannoma of the left facial nerve. The operation, which lasted for 10 h, was conducted under controlled hypotension. After the intervention the patient remained comatose with absent arm movements upon painful stimuli. An absent motor score usually carries a poor prognosis. However, magnetic resonance inversion recovery imaging of the brain showed bilateral hyperintense lesions in the arm-hand area indicative of borderzone ischemic damage. The patient received optimal supportive care and after 17 days he regained consciousness with 'man-in-the-barrel syndrome', which also further improved over time.

Variability of the autoregulation index decreases after removing the effect of the very low frequency band.

Dynamic cerebral autoregulation (dCA) estimates show large between and within subject variability. Sources of variability include low coherence and influence of CO2 in the very low frequency (VLF) band, where dCA is active. This may lead to unreliable transfer function and autoregulation index (ARI) estimates. We tested whether variability of the ARI could be decreased by suppressing the effect of the VLF band through filtering. We also evaluated whether filtering had any effect on mean group differences between healthy subjects and acute stroke patients. Data from a recent mobilization stroke study were re-analyzed. Middle cerebral artery cerebral blood flow velocity (MCA-CBFV), mean arterial blood pressure (MABP) and end tidal PCO2 (PetCO2) were obtained in 16 healthy subjects and 27 acute ischemic stroke patients in the supine position. The ARI index was calculated from the transfer function (TF) by using spontaneous BP fluctuations. Three different filtering strategies were compared; no filtering (NF), a high pass filter at 0.04 Hz (Time Domain Filtering: TDF) and a high pass Transfer Function Filter (TFF) at 0.04 Hz. In addition, a simulation study was done to obtain further insight into the effects of the applied filters. The variability of the ARI index decreased significantly only with TFF in healthy subjects (standard deviation (left vs. right) after NF 2.28 vs. 2.36, after TDF 2.13 vs. 2.31 after TFF 1.09 vs. 1.19, p<0.001). Variability was not significantly reduced in stroke patients. The mean ARI was significantly lower in stroke patients compared to healthy subjects after TFF (affected hemisphere 5.85±1.96 vs. 7.13±1.09, non-affected hemisphere 5.96±1.64 vs. 7.31±1.19, p<0.01 for both hemispheres), but not after NF or TDF. The simulation study showed that TFF results in an overestimation of the ARI index at low ARI levels (0-3), but in correct estimates at higher ARI levels. Removing the effect of the VLF band with TFF results in less ARI variability in healthy subjects, and in more pronounced group differences between stroke patients and healthy subjects. This will improve diagnostic properties when using TFA for ARI calculation.