Anesthesia and intraoperative neurophysiological spinal cord monitoring

Purpose of review We will explain the basic principles of intraoperative neurophysiological monitoring (IONM) during spinal surgery. Thereafter we highlight the significant impact that general anesthesia can have on the efficacy of the IONM and provide an overview of the essential pharmacological and physiological factors that need to be optimized to enable IONM. Lastly, we stress the importance of teamwork between the anesthesiologist, the neurophysiologist, and the surgeon to improve clinical outcome after spinal surgery. Recent findings In recent years, the use of IONM has increased significantly. It has developed into a mature discipline, enabling neurosurgical procedures of ever-increasing complexity. It is thus of growing importance for the anesthesiologist to appreciate the interplay between IONM and anesthesia and to build up experience working in a team with the neurosurgeon and the neurophysiologist. Safety measures, cooperation, careful choice of drugs, titration of drugs, and maintenance of physiological homeostasis are essential for effective IONM

Comparing navigated transcranial magnetic stimulation mapping and "gold standard" direct cortical stimulation mapping in neurosurgery:a systematic review

The objective of this systematic review is to create an overview of the literature on the comparison of navigated transcranial magnetic stimulation (nTMS) as a mapping tool to the current gold standard, which is (intraoperative) direct cortical stimulation (DCS) mapping. A search in the databases of PubMed, EMBASE, and Web of Science was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations were used. Thirty-five publications were included in the review, describing a total of 552 patients. All studies concerned either mapping of motor or language function. No comparative data for nTMS and DCS for other neurological functions were found. For motor mapping, the distances between the cortical representation of the different muscle groups identified by nTMS and DCS varied between 2 and 16 mm. Regarding mapping of language function, solely an object naming task was performed in the comparative studies on nTMS and DCS. Sensitivity and specificity ranged from 10 to 100% and 13.3-98%, respectively, when nTMS language mapping was compared with DCS mapping. The positive predictive value (PPV) and negative predictive value (NPV) ranged from 17 to 75% and 57-100% respectively. The available evidence for nTMS as a mapping modality for motor and language function is discussed

Optimal Parameters of Deep Brain Stimulation in Essential Tremor:A Meta-Analysis and Novel Programming Strategy

The programming of deep brain stimulation (DBS) parameters for tremor is laborious and empirical. Despite extensive efforts, the end-result is often suboptimal. One reason for this is the poorly understood relationship between the stimulation parameters' voltage, pulse width, and frequency. In this study, we aim to improve DBS programming for essential tremor (ET) by exploring a new strategy. At first, the role of the individual DBS parameters in tremor control was characterized using a meta-analysis documenting all the available parameters and tremor outcomes. In our novel programming strategy, we applied 10 random combinations of stimulation parameters in eight ET-DBS patients with suboptimal tremor control. Tremor severity was assessed using accelerometers and immediate and sustained patient-reported outcomes (PRO's), including the occurrence of side-effects. The meta-analysis showed no substantial relationship between individual DBS parameters and tremor suppression. Nevertheless, with our novel programming strategy, a significantly improved (accelerometer p = 0.02, PRO p = 0.02) and sustained (p = 0.01) tremor suppression compared to baseline was achieved. Less side-effects were encountered compared to baseline. Our pilot data show that with this novel approach, tremor control can be improved in ET patients with suboptimal tremor control on DBS. In addition, this approach proved to have a beneficial effect on stimulation-related complications

Are we on the right track in DBS surgery for dystonic head tremor?:Polymyography is a promising answer

The clinical benefit of Deep Brain Stimulation (DBS) is associated with electrode positioning accuracy. Intraoperative assessment of clinical effect is therefore key. Evaluating this clinical effect in patients with dystonic head tremor, as opposed to limb tremor, is challenging because the head is fixed in a stereotactic frame. To clinically assess head tremor during surgery, surface electromyography (EMG) electrodes were bilaterally applied to the sternocleidomastoid and cervical paraspinal muscles. This case shows that intraoperative polymyography is an easy and useful tool to assess the clinical effect of DBS electrode positioning

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 Society—Unified 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

Unusual course of Lafora disease

A 42-year-old male was admitted for refractory status epilepticus. At the age of 25, he had been diagnosed with juvenile myoclonic epilepsy. He had a stable clinical course for over a decade until a recent deterioration of behavior and epilepsy. After exclusion of acquired disorders, diagnostic work-up included application of next-generation sequencing (NGS), with a gene panel targeting progressive myoclonic epilepsies. This resulted in the diagnosis Lafora disease resulting from compound heterozygous NHLRC1 pathogenic variants. Although these pathogenic variants may be associated with a variable phenotype, including both severe and mild clinical course, the clinical presentation of our patient at this age is very unusual for Lafora disease. Our case expands the phenotype spectrum of Lafora disease resulting from pathogenic NHLRC1 variants and illustrates the value of using NGS in clinical practice to lead to a rapid diagnosis and guide therapeutic option

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

OBJECTIVE: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. METHODS: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP- (HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels. RESULTS: sNfL levels were increased both in 10 AL/PNP+ patients (p  I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p = .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age. CONCLUSION: sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis

Early electroencephalography for outcome prediction of postanoxic coma:A prospective cohort study

OBJECTIVE: To provide evidence that early electroencephalography (EEG) allows for reliable prediction of poor or good outcome after cardiac arrest.METHODS: In a 5-center prospective cohort study, we included consecutive, comatose survivors of cardiac arrest. Continuous EEG recordings were started as soon as possible and continued up to 5 days. Five-minute EEG epochs were assessed by 2 reviewers, independently, at 8 predefined time points from 6 hours to 5 days after cardiac arrest, blinded for patients' actual condition, treatment, and outcome. EEG patterns were categorized as generalized suppression (&lt;10 μV), synchronous patterns with ≥50% suppression, continuous, or other. Outcome at 6 months was categorized as good (Cerebral Performance Category [CPC] = 1-2) or poor (CPC = 3-5).RESULTS: We included 850 patients, of whom 46% had a good outcome. Generalized suppression and synchronous patterns with ≥50% suppression predicted poor outcome without false positives at ≥6 hours after cardiac arrest. Their summed sensitivity was 0.47 (95% confidence interval [CI] = 0.42-0.51) at 12 hours and 0.30 (95% CI = 0.26-0.33) at 24 hours after cardiac arrest, with specificity of 1.00 (95% CI = 0.99-1.00) at both time points. At 36 hours or later, sensitivity for poor outcome was ≤0.22. Continuous EEG patterns at 12 hours predicted good outcome, with sensitivity of 0.50 (95% CI = 0.46-0.55) and specificity of 0.91 (95% CI = 0.88-0.93); at 24 hours or later, specificity for the prediction of good outcome was &lt;0.90.INTERPRETATION: EEG allows for reliable prediction of poor outcome after cardiac arrest, with maximum sensitivity in the first 24 hours. Continuous EEG patterns at 12 hours after cardiac arrest are associated with good recovery. ANN NEUROL 2019.</p

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol

Background: To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. Methods/Design: We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. Discussion: The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases