Validity of the modified Rankin Scale in patients with aneurysmal subarachnoid hemorrhage: a randomized study.

PURPOSE: The modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs). METHODS: This is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses. RESULTS: In total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = - 0.546, while with RAND-36 physical and mental component scores the correlation was r = - 0.439and r = - 0.574 respectively, and with SS-QoL it was r = - 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was - 0.08 (SD 0.915). None of the hypotheses for responsiveness were met. CONCLUSION: The results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints. REGISTRATION: URL: https://trialsearch.who.int ; Unique identifier: NL7859, Date of first administration: 08-07-2019.

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.

Inter-method reliability of the modified Rankin Scale in patients with subarachnoid hemorrhage.

BACKGROUND AND OBJECTIVES: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS. METHODS: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire. RESULTS: The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible. DISCUSSION: The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials. TRIAL REGISTRATION: www.trialregister.nl ; Unique identifier: NL7859.

Low-frequency oscillation suppression in dystonia: Implications for adaptive deep brain stimulation.

BACKGROUND: Low-frequency oscillations (LFO) detected in the internal globus pallidus of dystonia patients have been identified as a physiomarker for adaptive Deep Brain Stimulation (aDBS), since LFO correlate with dystonic symptoms and are rapidly suppressed by continuous DBS (cDBS). However, it is as yet unclear how LFO should be incorporated as feedback for aDBS. OBJECTIVES: to test the acute effects of aDBS, using the amplitude of short-lived LFO-bursts to titrate stimulation, to explore the immediate effects of cDBS on LFO-modulation and dystonic symptoms, and to investigate whether a difference in the resting-state LFO is present between DBS-naïve patients and patients with chronic DBS. METHODS: seven patients were assessed during either DBS-implantation (n = 2) or battery replacement surgery (n = 5), and pseudorandomized in three conditions: no stimulation, cDBS, and aDBS. Additionally, resting-state LFP-recordings from patients undergoing battery replacement were compared to those obtained during DBS-implantation; LFP-recordings from a previous cohort of six dystonia patients undergoing DBS-implantation were incorporated into this analysis (total n = 8 newly implanted patients). RESULTS: we corroborated that a mild LFO-suppression rapidly occurs during cDBS. However, no acute changes in clinical symptoms were observed after cDBS or aDBS. Remarkably, we observed that resting-state LFO were significantly lower in patients who had been effectively treated with chronic cDBS compared to those of newly implanted patients, even when stimulation was suspended. CONCLUSIONS: our results indicate that LFO-suppression in dystonia, similar to symptom response to cDBS, might be gradual, and remain after stimulation is suspended. Therefore, tracking gradual changes in LFO may be required for aDBS implementation.

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.

An auditory brainstem implant for treatment of unilateral tinnitus: protocol for an interventional pilot study.

INTRODUCTION: Tinnitus may have a very severe impact on the quality of life. Unfortunately, for many patients, a satisfactory treatment modality is lacking. The auditory brainstem implant (ABI) was originally indicated for hearing restoration in patients with non-functional cochlear nerves, for example, in neurofibromatosis type II. In analogy to a cochlear implant (CI), it has been demonstrated that an ABI may reduce tinnitus as a beneficial side effect. For tinnitus treatment, an ABI may have an advantage over a CI, as cochlear implantation can harm inner ear structures due to its invasiveness, while an ABI is presumed to not damage anatomical structures. This is the first study to implant an ABI to investigate its effect on intractable tinnitus. METHODS AND ANALYSIS: In this pilot study, 10 adults having incapacitating unilateral intractable tinnitus and ipsilateral severe hearing loss will have an ABI implanted. The ABI is switched on 6 weeks after implantation, followed by several fitting sessions aimed at finding an optimal stimulation strategy. The primary outcome will be the change in Tinnitus Functioning Index. Secondary outcomes will be tinnitus burden and quality of life (using Tinnitus Handicap Inventory and Hospital Anxiety and Depression Scale questionnaires), tinnitus characteristics (using Visual Analogue Scale, a tinnitus analysis), safety, audiometric and vestibular function. The end point is set at 1 year after implantation. Follow-up will continue until 5 years after implantation. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Institutional Review Board of the University Medical Centre Groningen, The Netherlands (METc 2015/479). The trial is registered at www.clinicialtrials.gov and will be updated if amendments are made. Results of this study will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02630589. TRIAL STATUS: Inclusion of first patient in November 2017. Data collection is in progress. Trial is open for further inclusion. The trial ends at 5 years after inclusion of the last patient.

Direct comparison of oscillatory activity in the motor system of Parkinson's disease and dystonia: A review of the literature and meta-analysis.

OBJECTIVE: To outline the current knowledge of (sub)cortical oscillations in Parkinson's Disease (PD) and dystonia, and to quantitatively summarize the results of direct comparisons of local oscillatory power between both diseases in the resting state, without medication or stimulation, in both the low-frequency (LF, ±4-12 Hz) and beta (±13 to ∼30 Hz) range. METHODS: Eight relevant studies were included. Recordings from 127 dystonia-, and 144 PD-patient hemispheres were analyzed. Ratios of LF and beta power between diseases were obtained. RESULTS: Beta oscillations in dystonia were lower when compared to beta oscillations in PD, ratio = 0.72, Z = 3.56, p = 0.0004, 95% CI [0.60, 0.86]. Subgroup analyses showed significant differences only in the GPi, whilst conflicting evidence was shown in the STN. LF oscillations in PD were lower when compared to LF oscillations in dystonia, ratio = 0.77, Z = 2.45, p = 0.01, 95% CI [0.63, 0.95]. Subgroup analyses showed significant differences in the GPi and the STN, but not in the M1. CONCLUSIONS: LF and beta oscillations are present in the resting-state motor network of both PD and dystonia patients. However, the power distribution of those oscillations differs between diseases. SIGNIFICANCE: This meta-analysis provides high-level evidence which supports the presence of exaggerated oscillations across the parkinsonian/dystonic motor networks.

Mental versus physical fatigue after subarachnoid hemorrhage: differential associations with outcome.

BACKGROUND AND PURPOSE: Fatigue is a major consequence of subarachnoid hemorrhage (SAH), but the specific characteristics are unclear. Our objective was to investigate the nature of post-SAH fatigue (mental or physical) and to determine the relationship with functional outcome in the chronic stage. Also, the possible influence of mood disorders and acute SAH-related factors [SAH type and external cerebrospinal fluid (CSF) drainage] on the presence of fatigue was investigated. METHODS: Patients with an aneurysmal SAH (aSAH) or angiographically negative SAH (anSAH) were assessed 3-10 years post-SAH (N = 221). Questionnaires were used to investigate mental and physical fatigue and mood. Functional outcome was examined with the Glasgow Outcome Scale Extended. Between-group comparisons and binary logistic regression analysis were performed. RESULTS: Frequencies of mental and physical fatigue were 48.4% and 38.5%, respectively, with prevalence of mental fatigue being significantly higher. A two-way anova with SAH type and external CSF drainage as independent variables and mental fatigue as dependent variable showed a significant main effect of CSF drainage only (P < 0.001). Only mental fatigue explained a significant part of the variance in long-term functional outcome (model χ2 = 52.99, P < 0.001; Nagelkerke R² = 0.32). CONCLUSIONS: Mental fatigue after SAH is a serious burden to the patient and is associated with impaired long-term functional outcome. Distinguishing different aspects of fatigue is relevant as mental post-SAH fatigue might be a target for treatment aimed to improve long-term outcome.

Study protocol for a randomised controlled multicentre study: the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy.

INTRODUCTION: Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. METHODS AND ANALYSIS: The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. TRIAL REGISTRATION NUMBER: NTR5536, pre-results.

Outcome after intracranial haemorrhage from dural arteriovenous fistulae; a systematic review and case-series.

Dural arteriovenous fistulae (DAVFs) are a rare cause of intracranial haemorrhage. We aimed to investigate outcome of patients with intracranial haemorrhage from a DAVF. We performed a systematic literature search for studies reporting outcome after intracranial haemorrhage caused by a DAVF. We used predefined selection criteria and assessed the quality of the studies. In addition, we studied outcome in all patients with DAVF who had presented with intracranial haemorrhage at two university centers in the Netherlands, between January 2007 and April 2012. We calculated case fatality and proportions of patients with poor outcome (defined as modified Rankin Scale ≥ 3 or Glasgow Outcome Scale ≤ 3) during follow-up. We investigated mean age, sex, mid-year of study and percentage of patients with parenchymal haemorrhage as determinants of case fatality and poor outcome. The literature search yielded 16 studies, all but two retrospective and all hospital-based. Combined with our cohort of 29 patients the total number of patients with DAVF-related intracranial haemorrhage was 326 (58% intracerebral haemorrhage). At a median follow-up of 12 months case fatality was 4.7% (95% CI 2.5-7.5; 17 cohorts) and the proportion of patients with poor outcome 8.3% (95% CI 3.1-15.7; nine cohorts). We found no effect of mean age, sex, mid-year of the cohorts and percentage of patients with parenchymal haemorrhage on either outcome. Hospital based case-series suggest a relatively low risk of death and poor outcome in patients with intracranial haemorrhage due to rupture of a DAVF. These risks may be underestimated because of bias.

[Clipping comparable to coiling in intracranial aneurysm]. / Clippen gelijkwaardig aan coiling bij hersenaneurysma.

The 10-year follow-up results of the International Subarachnoid Aneurysm Trial essentially show the same results as the 5-year follow-up: no significant differences between endovascular coiling and neurosurgical clipping of ruptured intracranial aneurysms in terms of functional outcome (primary endpoint). The authors' statement that cumulative mortality rates still favour coiling did not hold up after modified intention-to-treat analysis had been performed. Moreover, the authors themselves show that survival between these treatment options is not significantly different. In the long term, coiling and clipping should therefore both be regarded viable treatment options.

[Epistaxis following skull trauma]. / Epistaxis na een schedeltrauma.

BACKGROUND: Epistaxis is a common problem, which is usually benign in nature. In some cases, however, epistaxis is a symptom of a severe underlying condition. CASE DESCRIPTION: A 20-year-old male was treated conservatively following head injury with craniofacial and base-of-skull fractures. Recurrent episodes of epistaxis occurred some weeks after treatment. Further investigation showed an extradural dissecting aneurysm of the left internal carotid artery (ICA), projecting into the sphenoid sinus. The aneurysm was treated endovascularly by placing a coil in the aneurism and a stent in the artery. On the basis of this case study we describe the diagnostics and treatment of patients with posttraumatic posterior epistaxis. CONCLUSION: In cases if delayed epistaxis following head injury the physician should be alert for the possibility of trauma to the ICA. This is a potentially life-threatening situation that requires prompt treatment.

[Treatment of trigeminal neuralgia]. / Behandeling van trigeminusneuralgie.

Classic idiopathic trigeminal neuralgia is characterized by sharp unilateral shooting pain in the distribution of one or more branches of the trigeminal nerve. It involves a diagnosis of exclusion. Initially, therapy consists of medical therapy, preferably with carbamazepine or oxcarbazepine. For patients refractory to medical therapy, microvascular decompression of the trigeminal nerve provides the best long-term outcomes, at a relatively low complication risk. In case of surgical contraindications, there are other options: radiosurgery or a neurodestructive procedure of the trigeminal ganglion. Short-term outcomes after neurodestructive therapy are good, however effects diminish over time. Every patient with idiopathic trigeminal neuralgia in whom medical therapy has failed, should be counselled at an experienced centre in which neurosurgical treatment is available.

Intracranial artery dissection.

The aim of this narrative review is to evaluate the pathogenesis, clinical features, diagnosis, treatment and prognosis of intracranial artery dissection (IAD). IAD is a rare and often unrecognized cause of stroke or subarachnoid haemorrhage (SAH), especially in young adults. Two types of IAD can be identified: a subintimal or subadventitial dissection. It is suggested that a subintimal dissection results in luminal stenosis, thromboembolism and subsequently cerebral ischaemia, whilst a subadventitial IAD could result in the formation of a pseudo-aneurysm and compression on brainstem or cranial nerves. Rupture of such a dissecting aneurysm causes SAH. The exact cause of IAD remains unknown but several factors are associated with its development. Diagnosis is based on clinical presentation and specific features seen on multimodal neuroimaging. The management of IAD depends on the clinical presentation. In the case of cerebral ischaemia, anticoagulants or antiplatelet agents are used, whilst in the case of SAH endovascular treatment is primarily advocated. Prognosis depends on clinical presentation. Presentation with SAH has a worse prognosis.

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.

Intracranial aneurysms in patients with subarachnoid hemorrhage: CT angiography as a primary examination tool for diagnosis--systematic review and meta-analysis.

PURPOSE: To calculate the sensitivity and specificity of computed tomographic (CT) angiography in the diagnosis of cerebral aneurysms in patients with acute subarachnoid hemorrhage (SAH) at presentation. MATERIALS AND METHODS: A systematic search for relevant studies was performed of the PubMed/MEDLINE and EMBASE databases. Two reviewers independently assessed the methodologic quality of each study by using the Quality Assessment of Diagnostic Accuracy Studies tool. The inclusion criteria were met by 50 studies. Heterogeneity was tested, and the presence of publication bias was visually assessed (by using a funnel plot). A meta-analysis of the reported sensitivity and specificity of each study with 95% confidence intervals (CIs) was performed on a per-patient level. RESULTS: Concerning sensitivity, the selected studies showed moderate heterogeneity. For specificity, low heterogeneity was observed. Moderate-heterogeneity studies that investigated only sensitivity or specificity were excluded from the pooled analyses by using a bivariate random effects model. The majority of the studies (n = 30) used a four-detector row CT scanner. The studies had good methodologic quality. Pooled sensitivity was 98% (95% CI: 97%, 99%), and pooled specificity was 100% (95% CI: 97%, 100%). Potential sources of variability among the studies were variations in the methodologic features (quality score), CT examination procedure (number of rows on the multidetector CT scanner), the standard of reference used, and the prevalence of ruptured intracranial aneurysms. There was evidence for publication bias, which may have led to overestimation of the diagnostic accuracy of CT angiography. CONCLUSION: Multidetector CT angiography can be used as a primary examination tool in the diagnostic work-up of patients with SAH.