11C-Methionine uptake in meningiomas after stereotactic radiotherapy.

OBJECTIVE: 11C-Methionine positron emission tomography (MET-PET) is used for stereotactic radiotherapy planning in meningioma patients. The role of MET-PET during subsequent follow-up (FU) is unclear. We analyzed the uptake of 11C-Methionine before and after stereotactic radiotherapy (SRT) in patients with a complex meningioma and investigated if there was a difference between patients with progressive disease (PD) and stable disease (SD) during FU. METHODS: This retrospective study investigates 62 MET-PETs in 29 complex meningioma patients. Standardized uptake value (SUV)max and SUVpeak tumor-to-normal ratios (T/N-ratios) were calculated, comparing the tumor region with both the mirroring intracranial area and the right frontal gray matter. The difference in 11C-Methionine uptake pre- and post-SRT was analyzed, as well as the change in uptake between PD or SD. RESULTS: Median (IQR) FU duration was 67 months (50.5-91.0). The uptake of 11C-Methionine in meningiomas remained increased after SRT. Neither a statistically significant difference between MET-PETs before and after SRT was encountered, nor a significant difference in one of the four T/N-ratios between patients with SD versus PD with median (IQR) SUVmax T/NR front 2.65 (2.13-3.68) vs 2.97 (1.55-3.54) [p = 0.66]; SUVmax T/Nmirror 2.92 (2.19-3.71) vs 2.95 (1.74-3.60) [p = 0.61]; SUVpeak T/NR front 2.35 (1.64-3.40) vs 2.25 (1.44-3.74) [p = 0.80]; SUVpeak T/Nmirror 2.38 (1.91-3.36) vs 2.35 (1.56-3.72) [p = 0.95]. CONCLUSIONS: Our data do not support use of MET-PET during FU of complex intracranial meningiomas after SRT. MET-PET could not differentiate between progressive or stable disease.

Tinnitus: an underreported condition following microvascular decompression for hemifacial spasm.

PURPOSE: While hearing loss is a well-known condition following microvascular decompression (MVD) for hemifacial spasm (HFS), tinnitus is an underreported one. This study aims to identify prevalence, characteristics, severity, and predictors of tinnitus following MVD for HFS. METHODS: A single-center cohort of 55 HFS patients completed a questionnaire approximately 5 years following MVD. Data encompassed tinnitus presence, side, type, onset, and severity measured by a 10-point Visual Analogue Scale (VAS). Descriptive, correlation, and logistic regression analyses were conducted. RESULTS  : At surgery, participants' median age was 58 years (IQR 52-65). The median duration of HFS symptoms before surgery was 5 years (IQR 3-8), slightly predominant on the left (60%). Postoperative tinnitus was reported by 20 patients (36%), versus nine (16%) that reported preoperative tinnitus. Postoperative tinnitus was ipsilateral on the surgical side in 13 patients (65%), bilateral in six (30%), and contralateral in one (5%). Among patients with bilateral postoperative tinnitus, 33% did not have this preoperatively. Tinnitus was continuous in 70% of cases and pulsatile in 30%. Onset of new tinnitus was in 58% immediately or within days, in 25% within three months, and in 17% between three months and one year after surgery. The mean severity of postoperative tinnitus was 5.1 points on the VAS. Preoperative tinnitus and presence of arachnoid adhesions had suggestive associations with postoperative tinnitus in initial analyses (p = 0.005 and p = 0.065). However, preoperative tinnitus was the only significant predictor of postoperative tinnitus (p = 0.011). CONCLUSION: Tinnitus is a common condition following MVD for HFS, with a moderate overall severity. Causes behind postoperative tinnitus remain obscure but could be related to those of postoperative hearing loss in this patient population. Clinicians should be aware of tinnitus following MVD and vigilantly monitor its occurrence, to facilitate prevention efforts and optimize outcome for HFS patients undergoing MVD.

Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.

OBJECTIVE: To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and TTR variant (TTRv) carriers. METHODS: sNfL levels were assessed longitudinally in persistently asymptomatic TTRv carriers (N = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (N = 8), in TTRv carriers who developed polyneuropathy (N = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (N = 20) or TTR-silencer (N = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay. RESULTS: sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic TTRv carriers. In all TTRv carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment. CONCLUSION: sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic TTRv carriers and in monitoring of disease progression and treatment effect.

Objective clinical registration of tremor, bradykinesia, and rigidity during awake stereotactic neurosurgery: a scoping review.

Tremor, bradykinesia, and rigidity are incapacitating motor symptoms that can be suppressed with stereotactic neurosurgical treatment like deep brain stimulation (DBS) and ablative surgery (e.g., thalamotomy, pallidotomy). Traditionally, clinicians rely on clinical rating scales for intraoperative evaluation of these motor symptoms during awake stereotactic neurosurgery. However, these clinical scales have a relatively high inter-rater variability and rely on experienced raters. Therefore, objective registration (e.g., using movement sensors) is a reasonable extension for intraoperative assessment of tremor, bradykinesia, and rigidity. The main goal of this scoping review is to provide an overview of electronic motor measurements during awake stereotactic neurosurgery. The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), articles were screened for relevance. Hundred-and-three articles were subject to detailed screening. Key clinical and technical information was extracted. The inclusion criteria encompassed use of electronic motor measurements during stereotactic neurosurgery performed under local anesthesia. Twenty-three articles were included. These studies had various objectives, including correlating sensor-based outcome measures to clinical scores, identifying optimal DBS electrode positions, and translating clinical assessments to objective assessments. The studies were highly heterogeneous in device choice, sensor location, measurement protocol, design, outcome measures, and data analysis. This review shows that intraoperative quantification of motor symptoms is still limited by variable signal analysis techniques and lacking standardized measurement protocols. However, electronic motor measurements can complement visual evaluations and provide objective confirmation of correct placement of the DBS electrode and/or lesioning. On the long term, this might benefit patient outcomes and provide reliable outcome measures in scientific research.

Intraoperative monitoring of the central and peripheral nervous systems: a narrative review.

The central and peripheral nervous systems are the primary target organs during anaesthesia. At the time of the inception of the British Journal of Anaesthesia, monitoring of the central nervous system comprised clinical observation, which provided only limited information. During the 100 yr since then, and particularly in the past few decades, significant progress has been made, providing anaesthetists with tools to obtain real-time assessments of cerebral neurophysiology during surgical procedures. In this narrative review article, we discuss the rationale and uses of electroencephalography, evoked potentials, near-infrared spectroscopy, and transcranial Doppler ultrasonography for intraoperative monitoring of the central and peripheral nervous systems.

The Association of Physiological and Pharmacological Anesthetic Parameters With Motor-Evoked Potentials: A Multivariable Longitudinal Mixed Model Analysis.

BACKGROUND: During spinal surgery, the motor tracts can be monitored using muscle-recorded transcranial electrical stimulation motor-evoked potentials (mTc-MEPs). We aimed to investigate the association of anesthetic and physiological parameters with mTc-MEPs. METHODS: Intraoperative mTc-MEP amplitudes, mTc-MEP area under the curves (AUC), and anesthetic and physiological measurements were collected retrospectively from the records of 108 consecutive patients undergoing elective spinal surgery. Pharmacological parameters of interest included propofol and opioid concentration, ketamine and noradrenaline infusion rates. Physiological parameters recorded included mean arterial pressure (MAP), bispectral index (BIS), heart rate, hemoglobin O2 saturation, temperature, and Etco2. A forward selection procedure was performed using multivariable mixed model analysis. RESULTS: Data from 75 (69.4%) patients were included. MAP and BIS were significantly associated with mTc-MEP amplitude (P < .001). mTc-MEP amplitudes increased by 6.6% (95% confidence interval [CI], 2.7%-10.4%) per 10 mm Hg increase in MAP and by 2.79% (CI, 2.26%-3.32%) for every unit increase in BIS. MAP (P < .001), BIS (P < .001), heart rate (P = .01), and temperature (P = .02) were significantly associated with mTc-MEP AUC. The AUC increased by 7.5% (CI, 3.3%-11.7%) per 10 mm Hg increase of MAP, by 2.98% (CI, 2.41%-3.54%) per unit increase in BIS, and by 0.68% (CI, 0.13%-1.23%) per beat per minute increase in heart rate. mTc-MEP AUC decreased by 21.4% (CI, -38.11% to -3.98%) per degree increase in temperature. CONCLUSIONS: MAP, BIS, heart rate, and temperature were significantly associated with mTc-MEP amplitude and/or AUC. Maintenance of BIS and MAP at the high normal values may attenuate anesthetic effects on mTc-MEPs.

Dorsal subthalamic nucleus targeting in deep brain stimulation: microelectrode recording versus 7-Tesla connectivity.

Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson's disease. It remains unclear whether deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 patients with Parkinson's disease, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus or non-motor-connected subthalamic nucleus, respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III) and microelectrode recording characteristics of multi- and single-unit activities were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared with electrodes placed in the non-motor-connected subthalamic nucleus (80% versus 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7-Tesla MRI subthalamic nucleus motor segment produced a superior clinical outcome; however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.

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.

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.

Supine MDS-UPDRS-III Assessment: An Explorative Study.

The Movement Disorder Society Unified Parkinson's Disease Rating Scale-part III (MDS-UPDRS-III) is designed to be applied in the sitting position. However, to evaluate the clinical effect during stereotactic neurosurgery or to assess bedridden patients with Parkinson's disease (PD), the MDS-UPDRS-III is often used in a supine position. This explorative study evaluates the agreement of the MDS-UPDRS-III in the sitting and the supine positions. In 23 PD patients, the MDS-UPDRS-III was applied in both positions while accelerometric measurements were performed. Video recordings of the assessments were evaluated by two certified raters. Agreement between the sitting and supine MDS-UPDRS-III was studied using Cohen's kappa coefficient. Relationships between the MDS-UPDRS-III tremor scores and accelerometric amplitudes were calculated for both positions with linear regression. A fair to substantial agreement was found for MDS-UPDRS-III scores of individual items in the sitting and supine positions, while combining all tests resulted in a substantial agreement. The inter-rater reliability was fair to moderate for both positions. A logarithmic relationship between tremor scores and accelerometric amplitude was revealed for both the sitting and supine positions. Nevertheless, these data are insufficient to fully support the supine application of the MDS-UPDRS-III. Several recommendations are made to address the sensitivity of the scale to inter-rater variability. In conclusion, although an overall substantial agreement between sitting and supine MDS-UPDRS-III is confirmed, its application in the supine position is not endorsed for the whole range of its individual items. Caution is warranted in interpreting the supine MDS-UPDRS-III, pending additional research.

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.

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).

Use of NEedle Versus suRFACE Recording Electrodes for Detection of Intraoperative Motor Warnings: A Non-Inferiority Trial. The NERFACE Study Part II.

In the NERFACE study part I, the characteristics of muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs) recorded from the tibialis anterior (TA) muscles with surface and subcutaneous needle electrodes were compared. The aim of this study (NERFACE part II) was to investigate whether the use of surface electrodes was non-inferior to the use of subcutaneous needle electrodes in detecting mTc-MEP warnings during spinal cord monitoring. mTc-MEPs were simultaneously recorded from TA muscles with surface and subcutaneous needle electrodes. Monitoring outcomes (no warning, reversible warning, irreversible warning, complete loss of mTc-MEP amplitude) and neurological outcomes (no, transient, or permanent new motor deficits) were collected. The non-inferiority margin was 5%. In total, 210 (86.8%) out of 242 consecutive patients were included. There was a perfect agreement between both recording electrode types for the detection of mTc-MEP warnings. For both electrode types, the proportion of patients with a warning was 0.12 (25/210) (difference, 0.0% (one-sided 95% CI, 0.014)), indicating non-inferiority of the surface electrode. Moreover, reversible warnings for both electrode types were never followed by permanent new motor deficits, whereas among the 10 patients with irreversible warnings or complete loss of amplitude, more than half developed transient or permanent new motor deficits. In conclusion, the use of surface electrodes was non-inferior to the use of subcutaneous needle electrodes for the detection of mTc-MEP warnings recorded over the TA muscles.

Comparing Motor-Evoked Potential Characteristics of NEedle versus suRFACE Recording Electrodes during Spinal Cord Monitoring-The NERFACE Study Part I.

Muscle-recorded transcranial electrical stimulation motor-evoked potentials (mTc-MEPs) are used to assess the spinal cord integrity. They are commonly recorded with subcutaneous needle or surface electrodes, but the different characteristics of mTc-MEP signals recorded with the two types of electrodes have not been formally compared yet. In this study, mTc-MEPs were simultaneously recorded from the tibialis anterior (TA) muscles using surface and subcutaneous needle electrodes in 242 consecutive patients. Elicitability, motor thresholds, amplitude, area under the curve (AUC), signal-to-noise ratio (SNR), and the variability between mTc-MEP amplitudes were compared. Whereas amplitude and AUC were significantly higher in subcutaneous needle recordings (p < 0.01), motor thresholds and elicitability were similar for surface and subcutaneous needle recordings. Moreover, the SNRs were >2 in more than 99.5% of the surface and subcutaneous needle recordings, and the variability between consecutive amplitudes was not significantly different between the two recording electrode types (p = 0.34). Surface electrodes appear to be a good alternative to needle electrodes for spinal cord monitoring. They are non-invasive, can record signals at similar threshold intensities, have adequately high SNRs, and record signals with equivalent variability. Whether surface electrodes are non-inferior to subcutaneous needle electrodes in detecting motor warnings is investigated in part II of the NERFACE study.

The Intraoperative Microlesion Effect Positively Correlates With the Short-Term Clinical Effect of Deep Brain Stimulation in Parkinson's Disease.

OBJECTIVE: During the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS. MATERIALS AND METHODS: Thirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout). RESULTS: Postinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01). CONCLUSION: The MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement.

STN-DBS electrode placement accuracy and motor improvement in Parkinson's disease: systematic review and individual patient meta-analysis.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective neurosurgical treatment for Parkinson's disease. Surgical accuracy is a critical determinant to achieve an adequate DBS effect on motor performance. A two-millimetre surgical accuracy is commonly accepted, but scientific evidence is lacking. A systematic review and meta-analysis of study-level and individual patient data (IPD) was performed by a comprehensive search in MEDLINE, EMBASE and Cochrane Library. Primary outcome measures were (1) radial error between the implanted electrode and target; (2) DBS motor improvement on the Unified Parkinson's Disease Rating Scale part III (motor examination). On a study level, meta-regression analysis was performed. Also, publication bias was assessed. For IPD meta-analysis, a linear mixed effects model was used. Forty studies (1391 patients) were included, reporting radial errors of 0.45-1.86 mm. Errors within this range did not significantly influence the DBS effect on motor improvement. Additional IPD analysis (206 patients) revealed that a mean radial error of 1.13±0.75 mm did not significantly change the extent of DBS motor improvement. Our meta-analysis showed a huge publication bias on accuracy data in DBS. Therefore, the current literature does not provide an unequivocal upper threshold for acceptable accuracy of STN-DBS surgery. Based on the current literature, DBS-electrodes placed within a 2 mm range of the intended target do not have to be repositioned to enhance motor improvement after STN-DBS for Parkinson's disease. However, an indisputable upper cut-off value for surgical accuracy remains to be established. PROSPERO registration number is CRD42018089539.

Brain death/death by neurologic criteria determination: an update.

PURPOSE OF REVIEW: Brain death, also known as death by neurologic criteria (DNC), is a well-established concept. In this article, we present a short history of the concept and give an overview of recent changes and a practical update on diagnosis and definitions of brain death/DNC. Unresolved issues will be discussed. RECENT FINDINGS: There is variability in brain death/DNC determination worldwide. In recent years, successful attempts have been made to harmonize these criteria and, consequently, to improve public trust in the process and diagnosis. An international multidisciplinary collaboration has been created and it has published minimum criteria, provided guidance for professionals and encouragement to revise or develop guidelines on brain death/DNC worldwide. SUMMARY: There are two sets of criteria for declaration of death. First, if there is neither cardiac output nor respiratory effort, then cardiopulmonary criteria are used. Second, if both the cerebrum and brainstem have completely and permanently lost all functions, and there is a persistent coma, absent brainstem reflexes and no spontaneous respiratory effort, death can be declared on the basis of brain death/DNC. Although attempts to formulate uniform criteria are ongoing, consensus has been reached on the minimum criteria. Some inconsistencies and questions remain.

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.

Outcome Prediction of Postanoxic Coma: A Comparison of Automated Electroencephalography Analysis Methods.

BACKGROUND: To compare three computer-assisted quantitative electroencephalography (EEG) prediction models for the outcome prediction of comatose patients after cardiac arrest regarding predictive performance and robustness to artifacts. METHODS: A total of 871 continuous EEGs recorded up to 3 days after cardiac arrest in intensive care units of five teaching hospitals in the Netherlands were retrospectively analyzed. Outcome at 6 months was dichotomized as "good" (Cerebral Performance Category 1-2) or "poor" (Cerebral Performance Category 3-5). Three prediction models were implemented: a logistic regression model using two quantitative features, a random forest model with nine features, and a deep learning model based on a convolutional neural network. Data from two centers were used for training and fivefold cross-validation (n = 663), and data from three other centers were used for external validation (n = 208). Model output was the probability of good outcome. Predictive performances were evaluated by using receiver operating characteristic analysis and the calculation of predictive values. Robustness to artifacts was evaluated by using an artifact rejection algorithm, manually added noise, and randomly flattened channels in the EEG. RESULTS: The deep learning network showed the best overall predictive performance. On the external test set, poor outcome could be predicted by the deep learning network at 24 h with a sensitivity of 54% (95% confidence interval [CI] 44-64%) at a false positive rate (FPR) of 0% (95% CI 0-2%), significantly higher than the logistic regression (sensitivity 33%, FPR 0%) and random forest models (sensitivity 13%, FPR, 0%) (p < 0.05). Good outcome at 12 h could be predicted by the deep learning network with a sensitivity of 78% (95% CI 52-100%) at a FPR of 12% (95% CI 0-24%) and by the logistic regression model with a sensitivity of 83% (95% CI 83-83%) at a FPR of 3% (95% CI 3-3%), both significantly higher than the random forest model (sensitivity 1%, FPR 0%) (p < 0.05). The results of the deep learning network were the least affected by the presence of artifacts, added white noise, and flat EEG channels. CONCLUSIONS: A deep learning model outperformed logistic regression and random forest models for reliable, robust, EEG-based outcome prediction of comatose patients after cardiac arrest.

Effects of targeted temperature management at 33 °C vs. 36 °C on comatose patients after cardiac arrest stratified by the severity of encephalopathy.

OBJECTIVES: To assess neurological outcome after targeted temperature management (TTM) at 33 °C vs. 36 °C, stratified by the severity of encephalopathy based on EEG-patterns at 12 and 24 h. DESIGN: Post hoc analysis of prospective cohort study. SETTING: Five Dutch Intensive Care units. PATIENTS: 479 adult comatose post-cardiac arrest patients. INTERVENTIONS: TTM at 33 °C (n = 270) or 36 °C (n = 209) and continuous EEG monitoring. MEASUREMENTS AND MAIN RESULTS: Outcome according to the cerebral performance category (CPC) score at 6 months post-cardiac arrest was similar after 33 °C and 36 °C. However, when stratified by the severity of encephalopathy based on EEG-patterns at 12 and 24 h after cardiac arrest, the proportion of good outcome (CPC 1-2) in patients with moderate encephalopathy was significantly larger after TTM at 33 °C (66% vs. 45%; Odds Ratios 2.38, 95% CI = 1.32-4.30; p = 0.004). In contrast, with mild encephalopathy, there was no statistically significant difference in the proportion of patients with good outcome between 33 °C and 36 °C (88% vs. 81%; OR 1.68, 95% CI = 0.65-4.38; p = 0.282). Ordinal regression analysis showed a shift towards higher CPC scores when treated with TTM 33 °C as compared with 36 °C in moderate encephalopathy (cOR 2.39; 95% CI = 1.40-4.08; p = 0.001), but not in mild encephalopathy (cOR 0.81 95% CI = 0.41-1.59; p = 0.537). Adjustment for initial cardiac rhythm and cause of arrest did not change this relationship. CONCLUSIONS: Effects of TTM probably depend on the severity of encephalopathy in comatose patients after cardiac arrest. These results support inclusion of predefined subgroup analyses based on EEG measures of the severity of encephalopathy in future clinical trials.