Diagnostic value of transcranial doppler to predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : To predict delayed cerebral ischemia.

BACKGROUND: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. METHODS: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. RESULTS: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5. CONCLUSION: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.

Haemosync: A synchronisation algorithm for multimodal haemodynamic signals.

BACKGROUND: Synchronous acquisition of haemodynamic signals is crucial for their multimodal analysis, such as dynamic cerebral autoregulation (DCA) analysis of arterial blood pressure (ABP) and transcranial Doppler (TCD)-derived cerebral blood velocity (CBv). Several technical problems can, however, lead to (varying) time-shifts between the different signals. These can be difficult to recognise and can strongly influence the multimodal analysis results. METHODS: We have developed a multistep, cross-correlation-based time-shift detection and synchronisation algorithm for multimodal pulsatile haemodynamic signals. We have developed the algorithm using ABP and CBv measurements from a dataset that contained combinations of several time-shifts. We validated the algorithm on an external dataset with time-shifts. We additionally quantitatively validated the algorithm's performance on a dataset with artificially added time-shifts, consisting of sample clock differences ranging from -0.2 to 0.2 s/min and sudden time-shifts between -4 and 4 s. The influence of superimposed noise and variation in waveform morphology on the time-shift estimation was quantified, and their influence on DCA-indices was determined. RESULTS: The instantaneous median absolute error (MedAE) between the artificially added time-shifts and the estimated time-shifts was 12 ms (median, IQR 12-12, range 11-14 ms) for drifts between -0.1 and 0.1 s/min and sudden time-shifts between -4 and 4 s. For drifts above 0.1 s/min, MedAE was higher (median 753, IQR 19 - 766, range 13 - 772 ms). When a certainty threshold was included (peak cross-correlation > 0.9), MedAE for all drifts-shift combinations decreased to 12 ms, with smaller variability (IQR 12 - 13, range 8 - 22 ms, p < 0.001). The time-shift estimation is robust to noise, as the MedAE was similar for superimposed white noise with variance equal to the signal variance. After time-shift correction, DCA-indices were similar to the original, non-time-shifted signals. Phase shift differed by 0.17° (median, IQR 0.13-0.2°, range 0.0038-1.1°) and 0.54° (median, IQR 0.23-1.7°, range 0.0088-5.6°) for the very low frequency and low frequency ranges, respectively. DISCUSSION: This algorithm allows visually interpretable detection and accurate correction of time-shifts between pulsatile haemodynamic signals (ABP and CBv).

The natural history of progressive myoclonus ataxia.

Progressive myoclonus ataxia (PMA) is a rare clinical syndrome characterized by the presence of progressive myoclonus and ataxia, and can be accompanied by mild cognitive impairment and infrequent epileptic seizures. This is the first study to describe the natural history of PMA and identify clinical, electrophysiological, and genetic features explaining the variability in disease progression. A Dutch cohort of consecutive patients meeting the criteria of the refined definition of PMA was included. The current phenotype was assessed during in-person consultation by movement disorders experts, and retrospective data was collected to describe disease presentation and progression, including brain imaging and therapy efficacy. Extensive genetic and electrophysiological tests were performed. The presence of cortical hyperexcitability was determined, by either the identification of a cortical correlate of myoclonic jerks with simultaneous electromyography-electroencephalography or a giant somatosensory evoked potential. We included 34 patients with PMA with a median disease duration of 15 years and a clear progressive course in most patients (76%). A molecular etiology was identified in 82% patients: ATM, CAMTA1, DHDDS, EBF3, GOSR2, ITPR1, KCNC3, NUS1, POLR1A, PRKCG, SEMA6B, SPTBN2, TPP1, ZMYND11, and a 12p13.32 deletion. The natural history is a rather homogenous onset of ataxia in the first two years of life followed by myoclonus in the first 5 years of life. Main accompanying neurological dysfunctions included cognitive impairment (62%), epilepsy (38%), autism spectrum disorder (27%), and behavioral problems (18%). Disease progression showed large variability ranging from an epilepsy free PMA phenotype (62%) to evolution towards a progressive myoclonus epilepsy (PME) phenotype (18%): the existence of a PMA-PME spectrum. Cortical hyperexcitability could be tested in 17 patients, and was present in 11 patients and supported cortical myoclonus. Interestingly, post-hoc analysis showed that an absence of cortical hyperexcitability, suggesting non-cortical myoclonus, was associated with the PMA-end of the spectrum with no epilepsy and milder myoclonus, independent of disease duration. An association between the underlying genetic defects and progression on the PMA-PME spectrum was observed. By describing the natural history of the largest cohort of published patients with PMA so far, we see a homogeneous onset with variable disease progression, in which phenotypic evolution to PME occurs in the minority. Genetic and electrophysiological features may be of prognostic value, especially the determination of cortical hyperexcitability. Furthermore, the identification of cortical and non-cortical myoclonus in PMA helps us gain insight in the underlying pathophysiology of myoclonus.

Time-domain methods for quantifying dynamic cerebral blood flow autoregulation: Review and recommendations. A white paper from the Cerebrovascular Research Network (CARNet).

Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA.

Negative Myoclonus: Neurophysiological Study and Clinical Impact in Progressive Myoclonus Ataxia.

INTRODUCTION: Negative myoclonus (NM) is an involuntary movement caused by a sudden interruption of muscular activity, resulting in gait problems and falls. OBJECTIVE: To establish frequency, clinical impact, and neurophysiology of NM in progressive myoclonus ataxia (PMA) patients. METHODS: Clinical, neurophysiological, and genetic data of 14 PMA individuals from University Medical Centre Groningen (UMCG) Expertise Center Movement Disorder Groningen were retrospectively collected. Neurophysiological examination included video-electromyography-accelerometry assessment in all patients and electroencephalography (EEG) examination in 13 individuals. Jerk-locked (or silent period-locked) back-averaging and cortico-muscular coherence (CMC) analysis aided the classification of myoclonus. RESULTS: NM was present in 6 (NM+) and absent in 8 (NM-) PMA patients. NM+ individuals have more frequent falls (100% vs. 37.5%) and higher scores on the Gross Motor Function Classification System (GMFCS) (4.3 ±0.74 vs. 2.5 ±1.2) than NM- individuals. Genetic background of NM+ included GOSR2 and SEMA6B, while that of NM- included ATM, KCNC3, NUS1, STPBN2, and GOSR2. NM was frequently preceded by positive myoclonus (PM) and silent-period length was between 88 and 194 ms. EEG epileptiform discharges were associated with NM in 2 cases. PM was classified as cortical in 5 NM+ and 2 NM- through EEG inspection, jerk-locked back-averaging, or CMC analysis. DISCUSSION: Neurophysiological examination is crucial for detecting NM that could be missed on clinical examination due to a preceding PM. Evidence points to a cortical origin of NM, an association with more severe motor phenotype, and suggests the presence of genetic disorders causing either a PMA or progressive myoclonus epilepsy, rather than pure PMA phenotype. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Instrumented Gait Classification Using Meaningful Features in Patients with Impaired Coordination.

Early onset ataxia (EOA) and developmental coordination disorder (DCD) both affect cerebellar functioning in children, making the clinical distinction challenging. We here aim to derive meaningful features from quantitative SARA-gait data (i.e., the gait test of the scale for the assessment and rating of ataxia (SARA)) to classify EOA and DCD patients and typically developing (CTRL) children with better explainability than previous classification approaches. We collected data from 18 EOA, 14 DCD and 29 CTRL children, while executing both SARA gait tests. Inertial measurement units were used to acquire movement data, and a gait model was employed to derive meaningful features. We used a random forest classifier on 36 extracted features, leave-one-out-cross-validation and a synthetic oversampling technique to distinguish between the three groups. Classification accuracy, probabilities of classification and feature relevance were obtained. The mean classification accuracy was 62.9% for EOA, 85.5% for DCD and 94.5% for CTRL participants. Overall, the random forest algorithm correctly classified 82.0% of the participants, which was slightly better than clinical assessment (73.0%). The classification resulted in a mean precision of 0.78, mean recall of 0.70 and mean F1 score of 0.74. The most relevant features were related to the range of the hip flexion-extension angle for gait, and to movement variability for tandem gait. Our results suggest that classification, employing features representing different aspects of movement during gait and tandem gait, may provide an insightful tool for the differential diagnoses of EOA, DCD and typically developing children.

The Relevance of Intraoperative Clinical and Accelerometric Measurements for Thalamotomy Outcome.

Thalamotomy alleviates medication-refractory tremors in patients with movement disorders such as Parkinson's Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However, limited data are available on tremor intensity during different thalamotomy stages. Also, the predictive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, we aimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered between January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patients with PD (n = 13), ET (n = 8), and HT (n = 3). MDS-UPDRS scores and tri-axial accelerometry data were obtained during rest, postural, and intention tremor tests. Measurements were performed intraoperatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) during coagulation, (4) directly after coagulation, and (5) 4-6 months post-surgery. Accelerometric data were recorded continuously during the coagulation process. Outcome measures included MDS-UPDRS tremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area under the curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1-2), during coagulation (3), post-coagulation effect (1-4), and postoperative effect (1-5). Following insertion and coagulation, tremor intensity improved significantly compared to baseline (p < 0.001). The insertion effect clearly correlated with the postoperative effect (ρ = 0.863, p < 0.001). Both tremor amplitude and AUCP declined gradually during coagulation. Peak frequency did not change significantly intraoperatively. In conclusion, the study data show that both the intraoperative insertion effect and the post-coagulation effect are good predictors for thalamotomy outcomes.

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation). METHODS: In this study, the rSO2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade. RESULTS: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade. CONCLUSIONS: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.

A Novel Accelerometry Method to Perioperatively Quantify Essential Tremor Based on Fahn-Tolosa-Marin Criteria.

The disease status, progression, and treatment effect of essential tremor (ET) patients are currently assessed with clinical scores, such as the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM). The use of objective and rater-independent monitoring of tremors may improve clinical care for patients with ET. Therefore, the focus of this study is to develop an objective accelerometry-based method to quantify ET, based on FTM criteria. Thirteen patients with ET and thirteen matched healthy participants underwent FTM tests to rate tremor severity, paired with tri-axial accelerometric measurements at the index fingers. Analogue FTM assessments were performed by four independent raters based on video recordings. Quantitative measures were derived from the accelerometric data, e.g., the area under the curve of power in the 4-8 Hz frequency band (AUCP) and maximal tremor amplitude. As such, accelerometric tremor scores were computed, using thresholds based on healthy measurements and FTM criteria. Agreement between accelerometric and clinical FTM scores was analyzed with Cohen's kappa coefficient. It was assessed whether there was a relationship between mean FTM scores and the natural logarithm (ln) of the accelerometric outcome measures using linear regression. The agreement between accelerometric and FTM scores was substantial for resting and intention tremor tests (≥72.7%). However, the agreement between accelerometric postural tremor data and clinical FTM ratings (κ = 0.459) was low, although their logarithmic (ln) relationship was substantial (R2 ≥ 0.724). Accelerometric test-retest reliability was good to excellent (ICC ≥ 0.753). This pilot study shows that tremors can be quantified with accelerometry, using healthy thresholds and FTM criteria. The test-retest reliability of the accelerometric tremor scoring algorithm indicates that our low-cost accelerometry-based approach is a promising one. The proposed easy-to-use technology could diminish the rater dependency of FTM scores and enable physicians to monitor ET patients more objectively in clinical, intraoperative, and home settings.

Ultra-high-definition (22 MHz) ultrasound of the ulnar nerve: additional value and normative data.

We studied 30 healthy volunteers (60 arms), categorized into three age groups with equal numbers to verify if a 22 MHz compared with a 15 MHz ultrasound transducer has additional value for studying the intraneural architecture of the ulnar nerve throughout its course. At six sites, there were no differences in cross-sectional area measurements between the two transducers. With both, the cross-sectional area was significantly larger at the medial epicondyle compared with the other sites and smaller at the mid-forearm and Guyon's canal compared with the mid-upper arm. With higher age the cross-sectional area significantly increased. Significantly more fascicles were visible distal to the medial epicondyle compared with more proximal sites, as well as in men compared with women. Finally, higher body weight was related to a significantly smaller number of fascicles being seen. A 22 MHz transducer depicts more details of the intraneural architecture than a 15 MHz transducer. Our data can be used as normative data or reference values in analysing ulnar nerve pathology.Level of evidence: II.

The Influence of Extracerebral Tissue on Continuous Wave Near-Infrared Spectroscopy in Adults: A Systematic Review of In Vivo Studies.

Near-infrared spectroscopy (NIRS) is a non-invasive technique for measuring regional tissue haemoglobin (Hb) concentrations and oxygen saturation (rSO2). It may be used to monitor cerebral perfusion and oxygenation in patients at risk of cerebral ischemia or hypoxia, for example, during cardiothoracic or carotid surgery. However, extracerebral tissue (mainly scalp and skull tissue) influences NIRS measurements, and the extent of this influence is not clear. Thus, before more widespread use of NIRS as an intraoperative monitoring modality is warranted, this issue needs to be better understood. We therefore conducted a systematic review of published in vivo studies of the influence of extracerebral tissue on NIRS measurements in the adult population. Studies that used reference techniques for the perfusion of the intra- and extracerebral tissues or that selectively altered the intra- or extracerebral perfusion were included. Thirty-four articles met the inclusion criteria and were of sufficient quality. In 14 articles, Hb concentrations were compared directly with measurements from reference techniques, using correlation coefficients. When the intracerebral perfusion was altered, the correlations between Hb concentrations and intracerebral reference technique measurements ranged between |r| = 0.45-0.88. When the extracerebral perfusion was altered, correlations between Hb concentrations and extracerebral reference technique measurements ranged between |r| = 0.22-0.93. In studies without selective perfusion modification, correlations of Hb with intra- and extracerebral reference technique measurements were generally lower (|r| < 0.52). Five articles studied rSO2. There were varying correlations of rSO2 with both intra- and extracerebral reference technique measurements (intracerebral: |r| = 0.18-0.77, extracerebral: |r| = 0.13-0.81). Regarding study quality, details on the domains, participant selection and flow and timing were often unclear. We conclude that extracerebral tissue indeed influences NIRS measurements, although the evidence (i.e., correlation) for this influence varies considerably across the assessed studies. These results are strongly affected by the study protocols and analysis techniques used. Studies employing multiple protocols and reference techniques for both intra- and extracerebral tissues are therefore needed. To quantitatively compare NIRS with intra- and extracerebral reference techniques, we recommend applying a complete regression analysis. The current uncertainty regarding the influence of extracerebral tissue remains a hurdle in the clinical implementation of NIRS for intraoperative monitoring. The protocol was pre-registered in PROSPERO (CRD42020199053).

Tremor, Daily Functioning, and Health-Related Quality of Life in Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTR) frequently report tremor. Data concerning tremor-related impairment and its potential impact on health-related quality of life (HRQoL) are lacking. This cross-sectional study assesses impact of tremor on activities of daily living and HRQoL using validated questionnaires among SOTR enrolled in the TransplantLines Biobank and Cohort Study. We included 689 SOTR (38.5% female, mean [±SD] age 58 [±14] years) at median [interquartile range] 3 [1-9] years after transplantation, of which 287 (41.7%) reported mild or severe tremor. In multinomial logistic regression analyses, whole blood tacrolimus trough concentration was an independent determinant of mild tremor (OR per µg/L increase: 1.11, 95% CI: 1.02 to 1.21, p = 0.019). Furthermore, in linear regression analyses, severe tremor was strongly and independently associated with lower physical and mental HRQoL (ß = -16.10, 95% CI: -22.23 to -9.98, p < 0.001 and ß = -12.68, 95% CI: -18.23 to -7.14, p < 0.001 resp.). SOTR frequently report tremor-related impairment of activities of daily living. Tacrolimus trough concentrations appeared as a main determinant of tremor among SOTR. The strong and independent association of tremor-related impairment with lower HRQoL warrants further studies into the effects of tacrolimus on tremor. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT03272841.

Muscular and kinematic features in speed skaters indicate a task-specific dystonia.

OBJECTIVE: Skater's cramp is a movement disorder in speed skaters. We investigated whether affected skaters matched the disease profile of task-specific dystonia, specifically whether there was evidence of maladaptive muscle activity occurring simultaneously with aberrant movements (jerking). We further examined different skating intensities, positing no change would be more indicative of task-specific dystonia. METHODS: We analyzed video, kinematic and muscle activity in 14 affected skaters. We measured the angular velocity and electromyographic activity of normalized speed skating strokes using one dimensional statistical non-parametric mapping. Skaters were matched with comparably skilled controls, and filled out a bespoke clinical questionnaire. RESULTS: Skaters' impacted leg showed over-activation in the peroneus longus, tibialis anterior and gastrocnemius that coincided with higher foot movement compared to their healthy leg and controls. This pattern persisted regardless of skating intensity. Clinical features indicated it was task-specific and painless with common trigger factors including stress, equipment change, and falling. CONCLUSIONS: We showed aberrant muscular and kinematic activity in a movement disorder in speed skaters indicative of task-specific dystonia. SIGNIFICANCE: Understanding skater's cramp as a task-specific dystonia could reduce the damage that misdiagnosis and unsuccessful invasive operations have caused. Our quantitative method has value in testing future treatment efficacy.

Near-infrared spectroscopy monitoring during endovascular treatment for acute ischaemic stroke.

Introduction: The aim of endovascular treatment (EVT) for acute ischaemic stroke is to relieve the cerebral tissue hypoxia in the area supplied by the occluded artery. Near-infrared spectroscopy (NIRS) monitoring is developed to assess regional cerebral tissue oxygen haemoglobin saturation (rSO2). We aimed to investigate whether NIRS can detect inter- and intra-hemispheric rSO2 differences during EVT. Patients and methods: In this prospective, observational study, patients undergoing EVT for a proximal intracranial occlusion of the anterior circulation between May 2019 and November 2020, were included. A four-wavelength NIRS monitor (O3® Regional Oximeter (Masimo, Irvine, CA)) was used to measure rSO2 during EVT with sensors placed over the temporal lobes in 20 patients and over the frontal lobes in 13 patients. The Wilcoxon signed-rank test was used to test for inter-hemispheric rSO2 differences after groin puncture and after recanalisation, and intra-hemispheric rSO2 changes before and after recanalisation. Results: In the temporal cohort, no inter-hemispheric rSO2 differences were observed after groin puncture (median [IQR] rSO2 affected hemisphere, 70% [67-73] and unaffected hemisphere, 70% [66-72]; p = 0.79) and after recanalisation. There were no intra-hemispheric rSO2 changes over time. In the frontal cohort, no inter- and intra-hemispheric rSO2 differences or changes were found. Discussion and conclusion: A NIRS monitor could not detect inter- and intra-hemispheric rSO2 differences or changes during EVT, irrespective of the sensor position. It is likely that even with temporal sensor application, a significant proportion of the received NIRS signal was influenced by oxygenation of surrounding tissues.

Cerebral Autoregulation Assessment Using the Near Infrared Spectroscopy 'NIRS-Only' High Frequency Methodology in Critically Ill Patients: A Prospective Cross-Sectional Study.

Impairments in cerebral autoregulation (CA) are related to poor clinical outcome. Near infrared spectroscopy (NIRS) is a non-invasive technique applied to estimate CA. Our general purpose was to study the clinical feasibility of a previously published 'NIRS-only' CA methodology in a critically ill intensive care unit (ICU) population and determine its relationship with clinical outcome. Bilateral NIRS measurements were performed for 1-2 h. Data segments of ten-minutes were used to calculate transfer function analyses (TFA) CA estimates between high frequency oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) signals. The phase shift was corrected for serial time shifts. Criteria were defined to select TFA phase plot segments (segments) with 'high-pass filter' characteristics. In 54 patients, 490 out of 729 segments were automatically selected (67%). In 34 primary neurology patients the median (q1-q3) low frequency (LF) phase shift was higher in 19 survivors compared to 15 non-survivors (13° (6.3-35) versus 0.83° (-2.8-13), p = 0.0167). CA estimation using the NIRS-only methodology seems feasible in an ICU population using segment selection for more robust and consistent CA estimations. The 'NIRS-only' methodology needs further validation, but has the advantage of being non-invasive without the need for arterial blood pressure monitoring.

Intraoperative Quantification of MDS-UPDRS Tremor Measurements Using 3D Accelerometry: A Pilot Study.

The most frequently used method for evaluating tremor in Parkinson's disease (PD) is currently the internationally standardized Movement Disorder Society­Unified PD Rating Scale (MDS-UPDRS). However, the MDS-UPDRS is associated with limitations, such as its inherent subjectivity and reliance on experienced raters. Objective motor measurements using accelerometry may overcome the shortcomings of visually scored scales. Therefore, the current study focuses on translating the MDS-UPDRS tremor tests into an objective scoring method using 3D accelerometry. An algorithm to measure and classify tremor according to MDS-UPDRS criteria is proposed. For this study, 28 PD patients undergoing neurosurgical treatment and 26 healthy control subjects were included. Both groups underwent MDS-UPDRS tests to rate tremor severity, while accelerometric measurements were performed at the index fingers. All measurements were performed in an off-medication state. Quantitative measures were calculated from the 3D acceleration data, such as tremor amplitude and area-under-the-curve of power in the 4−6 Hz range. Agreement between MDS-UPDRS tremor scores and objective accelerometric scores was investigated. The trends were consistent with the logarithmic relationship between tremor amplitude and MDS-UPDRS score reported in previous studies. The accelerometric scores showed a substantial concordance (>69.6%) with the MDS-UPDRS ratings. However, accelerometric kinetic tremor measures poorly associated with the given MDS-UPDRS scores (R2 < 0.3), mainly due to the noise between 4 and 6 Hz found in the healthy controls. This study shows that MDS-UDPRS tremor tests can be translated to objective accelerometric measurements. However, discrepancies were found between accelerometric kinetic tremor measures and MDS-UDPRS ratings. This technology has the potential to reduce rater dependency of MDS-UPDRS measurements and allow more objective intraoperative monitoring of tremor.

Electrophysiological testing aids the diagnosis of tremor and myoclonus in clinically challenging patients.

Objective: We investigated how clinical neurophysiological testing can help distinguish tremor and myoclonus and their subtypes. Methods: We retrospectively analysed clinical and neurophysiological data from patients who had undergone polymyography (EMG + accelerometry) to diagnose suspected tremor or myoclonus. We show a systematic approach, which includes contraction pattern, rhythm regularity, burst duration and evidence of cortical drive. Results: We detected 773 patients in our database, of which 556 patients were ultimately diagnosed with tremor (enhanced physiological tremor n = 169, functional tremor n = 140, essential tremor n = 90, parkinsonism associated tremor n = 64, cerebellar tremor n = 19, Holmes tremor n = 12, dystonic tremor n = 8, tremor not further specified n = 9), 140 with myoclonus and 23 with a combination of tremor and myoclonus. Polymyography confirmed the presumptive diagnosis in the majority of the patients and led to a change of diagnosis in 287 patients (37%). Conversions between diagnoses of tremor and myoclonus occurred most frequently between enhanced physiological tremor, essential tremor, functional tremor and cortical myoclonus. Conclusions: Neurophysiology is a valuable additional tool in clinical practice to differentiate between tremor and myoclonus, and can guide towards a specific subtype. Significance: We show how the stepwise neurophysiological approach used at our medical center aids the diagnosis of tremor versus myoclonus.

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. METHODS: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. RESULTS: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63). CONCLUSIONS: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome.

Near-Infrared Spectroscopy-Derived Dynamic Cerebral Autoregulation in Experimental Human Endotoxemia-An Exploratory Study.

Cerebral perfusion may be altered in sepsis patients. However, there are conflicting findings on cerebral autoregulation (CA) in healthy participants undergoing the experimental endotoxemia protocol, a proxy for systemic inflammation in sepsis. In the current study, a newly developed near-infrared spectroscopy (NIRS)-based CA index is investigated in an endotoxemia study population, together with an index of focal cerebral oxygenation. Methods: Continuous-wave NIRS data were obtained from 11 healthy participants receiving a continuous infusion of bacterial endotoxin for 3 h (ClinicalTrials.gov NCT02922673) under extensive physiological monitoring. Oxygenated-deoxygenated hemoglobin phase differences in the (very)low frequency (VLF/LF) bands and the Tissue Saturation Index (TSI) were calculated at baseline, during systemic inflammation, and at the end of the experiment 7 h after the initiation of endotoxin administration. Results: The median (inter-quartile range) LF phase difference was 16.2° (3.0-52.6°) at baseline and decreased to 3.9° (2.0-8.8°) at systemic inflammation (p = 0.03). The LF phase difference increased from systemic inflammation to 27.6° (12.7-67.5°) at the end of the experiment (p = 0.005). No significant changes in VLF phase difference were observed. The TSI (mean ± SD) increased from 63.7 ± 3.4% at baseline to 66.5 ± 2.8% during systemic inflammation (p = 0.03) and remained higher at the end of the experiment (67.1 ± 4.2%, p = 0.04). Further analysis did not reveal a major influence of changes in several covariates such as blood pressure, heart rate, PaCO2, and temperature, although some degree of interaction could not be excluded. Discussion: A reversible decrease in NIRS-derived cerebral autoregulation phase difference was seen after endotoxin infusion, with a small, sustained increase in TSI. These findings suggest that endotoxin administration in healthy participants reversibly impairs CA, accompanied by sustained microvascular vasodilation.