Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Visual symptoms in postural tachycardia syndrome: An investigation of position-dependent visual exploration.

BACKGROUND AND PURPOSE: Patients with postural tachycardia syndrome report position-dependent visual symptoms. Despite their impact on daily life, these symptoms have remained largely unexplored in research. The aim of this study was to investigate the nature of visual symptoms in postural tachycardia syndrome and possible underlying pathophysiological mechanisms. METHODS: Fifteen patients with postural tachycardia syndrome and 15 healthy controls were included in the study. Through a comprehensive array of measurements, including haemodynamics, subjective symptom assessments, eye movement tracking and pupil diameter analysis, participants were assessed during free image exploration in both supine and 60° head-up tilt positions. RESULTS: During head-up tilt, patients showed a decreased number and duration of fixations, as well as a decreased number, peak velocity and amplitude of saccades compared to the supine position and the control group. This reduction in visual exploration occurred primarily in the peripheral field of view and coincided with the occurrence of subjective visual symptoms. No significant differences in the saccade main sequence were observed between the two groups in either body position. CONCLUSIONS: Patients with postural tachycardia syndrome have a reduced exploration of the peripheral field of view when in an upright body position, potentially leading to tunnel vision. Since the normality of the saccade main sequence in patients combined with the focus on the centre of the field of view and the lower saccade amplitudes points to an intact brainstem function, the decrease in peripheral visual exploration may be attributed to a position-dependent dysfunction of the frontal eye field.

Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.

Time for "code ICH"? - Workflow metrics of hyperacute treatments and outcome in patients with intracerebral haemorrhage.

INTRODUCTION: Knowledge about uptake and workflow metrics of hyperacute treatments in patients with non-traumatic intracerebral haemorrhage (ICH) in the emergency department are scarce. METHODS: Single centre retrospective study of consecutive patients with ICH between 01/2018-08/2020. We assessed uptake and workflow metrics of acute therapies overall and according to referral mode (stroke code, transfer from other hospital or other). RESULTS: We enrolled 332 patients (age 73years, IQR 63-81 and GCS 14 points, IQR 11-15, onset-to-admission-time 284 minutes, IQR 111-708minutes) of whom 101 patients (35%) had lobar haematoma. Mode of referral was stroke code in 129 patients (38%), transfer from other hospital in 143 patients (43%) and arrival by other means in 60 patients (18%). Overall, 143 of 216 (66%) patients with systolic blood pressure >150mmHG received IV antihypertensive and 67 of 76 (88%) on therapeutic oral anticoagulation received prothrombin complex concentrate treatment (PCC). Forty-six patients (14%) received any neurosurgical intervention within 3 hours of admission. Median treatment times from admission to first IV-antihypertensive treatment was 38 minutes (IQR 18-72minutes) and 59 minutes (IQR 37-111 minutes) for PCC, with significant differences according to mode of referral (p<0.001) but not early arrival (≤6hours of onset, p=0.92). The median time in the emergency department was 139 minutes (IQR 85-220 minutes) and among patients with elevated blood pressure, only 44% achieved a successful control (<140mmHG) during ED stay. In multivariate analysis, code ICH concordant treatment was associated with significantly lower odds for in-hopsital mortality (aOR 0.30, 95%CI 0.12-0.73, p=0.008) and a non-significant trends towards better functional outcome measured using the modified Rankin scale score at 3 months (aOR for ordinal shift 0.54 95%CI 0.26-1.12, p=0.097). CONCLUSION: Uptake of hyperacute therapies for ICH treatment in the ED is heterogeneous. Treatment delays are short but not all patients achieve treatment targets during ED stay. Code ICH concordant treatment may improve clinical outcomes. Further improvements seem achievable advocating for a "code ICH" to streamline acute treatments.

Prevalence of Painful Temporomandibular Disorder Symptoms Among Professional and Student Musicians: An Online Survey.

BACKGROUND: Within the fields of medicine and music, increasing attention is given to evidence indicating music performance being an occupational risk factor for temporo-mandibular disorders (TMD). OBJECTIVES: Assessment of self-reported painful TMD symptoms among student and professional musicians. METHODS: Using Survey Monkey software, the German version of the 'TMD-Pain-Screener' was distributed electronically to professional and student musicians in Europe. Supplementary questions addressed age, gender, daily playtime, instrument type and type of professional practice. Results are presented as median [interquartile range]. RESULTS: The TMD-pain-screener was completed by 492 participants. Among them, 96 (19.5%) reported painful TMD (Pain_pos) and 396 did not experience pain (80.5%, Pain_neg). Pain_pos participants were significantly younger (Pain_pos: 34 years [26; 46], Pain_neg: 44 years [30; 56], p = 0.0003), had less work experience (Pain_pos: 15.5 years [6; 25], Pain_neg: 20 years [10; 32], p = 0.009), had fewer performances/year (Pain_pos: 20/year [10; 45], Pain_neg: 30/year [12; 53.5], p = 0.03) and were predominantly female (OR = 3.22 [1.87, 5.74], p < 0.0001). Comparisons among music performance types revealed no statistical significance in the overall test (p = 0.13), although 'keyboard' (OR = 2.99 [0.58, 30.12]), 'upper string' (OR = 2.31 [0.43, 23.63]) and 'singer' (OR = 2.14 [0.44, 20.75]) stood out compared to the reference group 'lower string' (OR 1.00). Organ players formed the largest group and showed a comparatively low prevalence of Pain_pos (16%), compared to other keyboard instruments (Pain_pos 30.2%). CONCLUSIONS: Prevalence of TMD pain was highest among young inexperienced female musicians. Playing keyboard instruments (other than organ) or upper strings instruments were frequently associated with painful TMD screening. An improved understanding of causes, implementation of preventive measures, professional guidance and a biopsychosocial health care perspective may decrease this occupational risk while maintaining the health benefits of music.

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients.

BACKGROUND: The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition. METHODS: A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated. RESULTS: MSTN gene expression (median [IQR] fold change: 1.00 [0.68-1.54] vs. 0.26 [0.11-0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways. CONCLUSION: Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients. TRIAL REGISTRATION: ISRCTN77569430 -13th of February 2008 and ISRCTN19392591 17th of February 2011.

Ultrasound Perfusion Imaging for the Detection of Cerebral Hypoperfusion After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia increases mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Various techniques are applied to detect cerebral vasospasm and hypoperfusion. Contrast-enhanced ultrasound perfusion imaging (UPI) is able to detect cerebral hypoperfusion in acute ischemic stroke. This prospective study aimed to evaluate the use of UPI to enable detection of cerebral hypoperfusion after aSAH. METHODS: We prospectively enrolled patients with aSAH and performed UPI examinations every second day after aneurysm closure. Perfusion of the basal ganglia was outlined to normalize the perfusion records of the anterior and posterior middle cerebral artery territory. We applied various models to characterize longitudinal perfusion alterations in patients with delayed ischemic neurologic deficit (DIND) across the cohort and predict DIND by using a multilayer classification model. RESULTS: Between August 2013 and December 2015, we included 30 patients into this prospective study. The left-right difference of time to peak (TTP) values showed a significant increase at day 10-12. Patients with DIND demonstrated a significant, 4.86 times increase of the left-right TTP ratio compared with a mean fold change in patients without DIND of 0.9 times (p = 0.032). CONCLUSIONS: UPI is feasible to enable detection of cerebral tissue hypoperfusion after aSAH, and the left-right difference of TTP values is the most indicative result of this finding.

Electrical Stimulation for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Systematic Review.

OBJECTIVES: Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable. Electrical stimulation may have a considerable influence on cerebrovascular innervation. This systematic review gives an overview of the studies that have applied electrical stimulation in models of cerebral vasospasm. MATERIALS AND METHODS: We performed a systematic review of the literature, searching PubMed and Ovid Embase with the keywords "electric stimulation," "cerebral vasospasm," "subarachnoid hemorrhage," "sympathetic," and "parasympathetic." Additional papers were identified from the reference lists of the articles identified in the literature search. RESULTS: Increased cerebral blood flow (CBF) is a widely observed effect of spinal cord stimulation and sphenopalatine ganglion stimulation in models of physiological conditions or experimental cerebral vasospasm. Most studies were conducted in animals, 15 under physiological conditions and 11 in animals with SAH. Eight studies in humans were identified that examined the stimulation effect on CBF under physiological conditions. Only two studies looked at patients after SAH: one applied spinal cord stimulation (SCS) and the other transcutaneous electrical neurostimulation. Different mechanisms leading to stimulation-induced CBF increase that were discussed included "reversible functional sympathectomy," activation of brainstem vasomotor centers, involvement of central ascending pathways, release of neurohumoral factors, and interaction with sympathetic, parasympathetic, and trigeminal innervation. The results indicate that electrical stimulation is a promising procedure for prevention and treatment of cerebral vasospasm. CONCLUSION: Electrical stimulation, especially SCS and sphenopalatine ganglion stimulation, is a promising adjunct for existing therapies for vasospasm after SAH. Further experiments and prospective clinical studies are needed to establish its potential usefulness as a therapy or prevention option.

Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage: The Swiss Study on Subarachnoid Hemorrhage (Swiss SOS).

BACKGROUND AND PURPOSE: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. METHODS: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. RESULTS: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0-2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3-5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. CONCLUSIONS: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03245866.

Effect of intermittent high-frequency stimulation on muscle velocity recovery cycle recordings.

The technique of multifiber muscle velocity recovery cycle recordings was developed as a diagnostic tool to assess muscle membrane potential changes and ion channel function in vivo. This study was undertaken to assess the impact of intermittent high-frequency stimulation on muscle velocity recovery cycle components and to study whether the changes can be modified by endurance training. We recorded muscle velocity recovery cycles with 1 and 2 conditioning stimuli in the left tibialis anterior muscle in 15 healthy subjects during intermittent 37-Hz stimulation and analyzed its effects on the different phases of supernormality. Recordings were conducted before and after 2-wk endurance training. Training effect was assessed by measuring the difference in endurance time, peak force, and limb circumference. Muscle velocity recovery cycle recordings during intermittent high-frequency stimulation were successfully recorded in 12 subjects. Supernormality for interstimulus intervals shorter than 15 ms (early supernormality) was maximally reduced at the beginning of repetitive stimulation and recovered during stimulation. Supernormality for interstimulus intervals between 50 and 150 ms (late supernormality) showed a delayed decrease and stayed significantly reduced after high-frequency stimulation. Training had no significant effect on any of the measured parameters, but we found that training induced changes in peak force correlated positively with baseline changes of early supernormality. Our results support the hypothesis that early supernormality represents membrane potential, which depolarizes in the beginning of high-frequency stimulation. Late supernormality probably reflects transverse tubular function and shows progressive changes during high-frequency stimulation with delayed normalization.NEW & NOTEWORTHY A conditioning impulse in human muscle fibers induces a prolonged phase of increased velocity (also called supernormality) with two phases related to an early and late afterpotential. We investigated the effects of intermittent 37-Hz stimulation on muscle fiber supernormality and found that the early and late phases of supernormality changed differently, and that the late phase may reflect the ionic interactions responsible for the counter-regulation of muscle fatigue.

Immunomodulatory treatment in postural tachycardia syndrome: A case series.

BACKGROUND AND PURPOSE: Postural tachycardia syndrome (POTS) is a form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. Recently, evidence has accumulated that in a subset of patients, the pathogenesis of dysautonomia may be immune-mediated. The aim of the current report was to evaluate the use of intravenous immunoglobulin (IVIG) treatment in patients with progressive and/or refractory immune-mediated POTS. METHODS: We retroactively assessed the effect and tolerance of monthly administered IVIG in six patients using autonomic function testing, standardized symptom questionnaires, and patients' symptom diaries both before and 6 months into IVIG treatment. Objective outcome measures included heart rate increase after 10 min of head-up tilt as well as duration and anhidrotic area in a thermoregulatory sweat test. Subjective outcome measures were patient reports and symptom ratings from the symptom questionnaire. RESULTS: All patients responded to immunomodulatory treatment, regardless of disease duration. After 6 months of IVIG, symptom severity was reduced by nearly 40%. Autonomic function testing showed improved cardiovascular functioning by 50% and a reduction of anhidrotic areas by one third. Overall, tolerance of IVIG treatment was poor, but could be improved by a reduction in infusion rate, premedication with steroids, and additional intravenous hydration. CONCLUSIONS: Using subjective but also standardized objective measures, the case series describes promising effects of IVIG treatment in POTS patients with immune-mediated dysautonomia. By reducing the infusion rate, pretreatment with steroids, and intravenous hydration, tolerance could be improved, and no patient had to discontinue the treatment.

Leg pain in neuropathic postural tachycardia syndrome is associated with altered muscle membrane properties.

PURPOSE: In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report leg pain and weakness in the upright position. To explore possible pathophysiological processes underlying these symptoms, the present study examined muscle excitability depending on body position in patients with neuropathic postural tachycardia syndrome and healthy subjects. METHODS: In ten patients with neuropathic postural tachycardia syndrome and ten healthy subjects, muscle excitability measurements were performed repeatedly: in the supine position, during 10 min of head-up tilt and during 6 min thereafter. Additionally, lower leg circumference was measured and subjective leg pain levels were assessed. RESULTS: In patients with neuropathic postural tachycardia syndrome, muscle excitability was increased in the supine position, decreased progressively during tilt, continued to decrease after being returned to the supine position, and did not completely recover to baseline values after 6 min of supine rest. The reduction in muscle excitability during tilt was paralleled by an increase in lower leg circumference as well as leg pain levels. No such changes were observed in healthy subjects. CONCLUSIONS: This study provides evidence for the occurrence of orthostatic changes in muscle excitability in patients with neuropathic postural tachycardia syndrome and that these may be associated with inadequate perfusion of the lower extremities. Insufficient perfusion as a consequence of blood stasis may cause misery perfusion of the muscles, which could explain the occurrence of orthostatic leg pain in neuropathic postural tachycardia syndrome.

Individualized Brain Tissue Oxygen-Monitoring Probe Placement Helps to Guide Therapy and Optimizes Outcome in Neurocritical Care.

BACKGROUND/OBJECTIVE: In order to monitor tissue oxygenation in patients with acute neurological disorders, probes for measurement of brain tissue oxygen tension (ptO2) are often placed non-specifically in a right frontal lobe location. To improve the value of ptO2 monitoring, placement of the probe into a specific area of interest is desirable. We present a technique using CT-guidance to place the ptO2 probe in a particular area of interest based on the individual patient's pathology. METHODS: In this retrospective cohort study, we analyzed imaging and clinical data from all patients who underwent CT-guided ptO2 probe placement at our institution between October 2017 and April 2019. Primary endpoint was successful placement of the probe in a particular area of interest rated by two independent reviewers. Secondary outcomes were complications from probe insertion, clinical consequences from ptO2 measurements, clinical outcome according to the modified Rankin Scale (mRS) as well as development of ischemia on follow-up imaging. A historical control group was selected from patients who underwent conventional ptO2 probe placement between January 2010 and October 2017. RESULTS: Eleven patients had 16 CT-guided probes inserted. In 15 (93.75%) probes, both raters agreed on the correct placement in the area of interest. Each probe triggered on average 0.48 diagnostic or therapeutic adjustments per day. Only one infarction within the vascular territory of a probe was found on follow-up imaging. Eight out of eleven patients (72.73%) reached a good outcome (mRS ≤ 3). In comparison, conventionally placed probes triggered less diagnostic and therapeutic adjustment per day (p = 0.007). Outcome was worse in the control group (p = 0.024). CONCLUSION: CT-guided probe insertion is a reliable and easy technique to place a ptO2 probe in a particular area of interest in patients with potentially reduced cerebral oxygen supply. By adjusting treatment aggressively according to this individualized monitoring data, clinical outcome may improve.

[Intracerebral haemorrhage - acute event and chronic disease]. / Die intrazerebrale Hirnblutung: Akutes Ereignis und chronische Erkrankung.

Intracerebral haemorrhage - acute event and chronic disease Abstract. Intracerebral hemorrhage accounts for 10-15% of all strokes and approximately 1'500-2'000 patients per year in Switzerland. Acute treatment by multi-disciplinary experts at certified stroke units and stroke centers is important to provide optimal care. A simple ABC-care bundle (revert anticoagulation, control blood pressure, inform neurosurgeon) decreases poor outcome. Despite a high mortality, one third of patients are functionally independent after intracerebral hemorrhage contradicting widespread pessimism. About 80% of all intracerebral hemorrhage are attributable to different types of cerebral small vessel disease. Relative and absolute risks of recurrent hemorrhage and ischemic stroke differ significantly. Patients with intracerebral hemorrhage are vascular high-risk patients with chronic cerebrovascular disease. Long-term outpatient management should include neurovascular specialists to deal with important decisions (blood pressure management, antithrombotic therapy including anticoagulation, specialized neurorehabilitation to improve neurocognitive deficits, therapy of possible complications such as epilepsy) to provide optimal and individual care to patients. Currently ongoing randomized controlled trials will provide important results in the next years further improving treatment of intracerebral hemorrhage.

Defense mechanisms to increasing back pressure for hepatic oxygen transport and venous return in porcine fecal peritonitis.

High central venous pressure (CVP) acutely decreases venous return. How this affects hepatic oxygen transport in sepsis remains unclear. The aim of this study was to evaluate the effects of repeated increases in CVP via standard nursing procedures (NPs) on hepato-splanchnic and renal oxygen transport in a prolonged porcine sepsis model. Twenty anesthetized and mechanically ventilated pigs with regional hemodynamics monitored were randomized to fecal peritonitis or controls (n = 10 pigs/group). Resuscitation was started after 8 h of observation and continued for 3 days. NPs were performed at baseline and 8 h, 32 h, 56 h, and 72 h after resuscitation started. NPs increased CVP by 4-7 mmHg in both groups. In controls, this was associated with less decrease in hepatic arterial (Qha; 62 ± 70 mL/min) than portal venous flow (Qpv; 364 ± 151 mL/min). Portal venous oxygen content and hepatic O2 delivery (Do2) and consumption (V̇o2) decreased by 11 ± 6 mL/dL and 0.9 ± 0.3 and 0.4 ± 0.3 mL·min-1·kg-1, respectively. In septic animals, hepatic Do2 decreased more in response to increasing CVP (1.5 ± 0.9 mL·min-1·kg-1), which was attributable to a larger fall in both Qha (88 ± 66 ml/min) and portal O2 content (14 ± 10 mL/dL, all P < 0.05). This resulted in numerically lower hepatic V̇o2 since O2 extraction did not increase significantly. In control conditions, a smaller decrease in Qha compared with Qpv helped to limit the reduction in hepatic V̇o2 in response to acute CVP increase. In sepsis, the contribution of Qha to maintain hepatic Do2 was reduced, which jeopardized hepatic V̇o2 further. Renal arterial flow was similarly affected by CVP increase as Qha.NEW & NOTEWORTHY Sepsis impairs intrinsic mechanisms to attenuate effects of increasing back pressure on hepatic oxygen transport.

SCN8A heterozygous variants are associated with anoxic-epileptic seizures.

Anoxic-epileptic seizures (AES) are rare outcomes of common childhood reflex anoxic syncope that trigger a true epileptic seizure. The term AES was coined by Stephenson in 1983, to differentiate these events from convulsive syncopes and the more common reflex anoxic syncopes. A genetic susceptibility for AES has been postulated; but, its molecular basis has up to now been elusive. We report here two illustrative cases and show the association of de novo SCN8A variants and AES. One of them had focal or generalized seizures and autonomic symptoms triggered by orthostatism; the second had breath-holding spells triggered by pain or exercise leading to tonic-clonic seizures; both had repeatedly normal EEGs and a family history of reflex syncope. The data of three additional AES patients further suggest, for the first time, a link between SCN8A pathogenic variants and AES. The neurodevelopment of four patients was abnormal. Four of the five SCN8A mutations observed here were previously described in patients with seizure disorders. Seizures responded particularly well to sodium channel blockers. Our observation enriches the spectrum of seizures linked with SCN8A pathogenic variants.

Standardized visual EEG features predict outcome in patients with acute consciousness impairment of various etiologies.

BACKGROUND: Early prognostication in patients with acute consciousness impairment is a challenging but essential task. Current prognostic guidelines vary with the underlying etiology. In particular, electroencephalography (EEG) is the most important paraclinical examination tool in patients with hypoxic ischemic encephalopathy (HIE), whereas it is not routinely used for outcome prediction in patients with traumatic brain injury (TBI). METHOD: Data from 364 critically ill patients with acute consciousness impairment (GCS ≤ 11 or FOUR ≤ 12) of various etiologies and without recent signs of seizures from a prospective randomized trial were retrospectively analyzed. Random forest classifiers were trained using 8 visual EEG features-first alone, then in combination with clinical features-to predict survival at 6 months or favorable functional outcome (defined as cerebral performance category 1-2). RESULTS: The area under the ROC curve was 0.812 for predicting survival and 0.790 for predicting favorable outcome using EEG features. Adding clinical features did not improve the overall performance of the classifier (for survival: AUC = 0.806, p = 0.926; for favorable outcome: AUC = 0.777, p = 0.844). Survival could be predicted in all etiology groups: the AUC was 0.958 for patients with HIE, 0.955 for patients with TBI and other neurosurgical diagnoses, 0.697 for patients with metabolic, inflammatory or infectious causes for consciousness impairment and 0.695 for patients with stroke. Training the classifier separately on subgroups of patients with a given etiology (and thus using less training data) leads to poorer classification performance. CONCLUSIONS: While prognostication was best for patients with HIE and TBI, our study demonstrates that similar EEG criteria can be used in patients with various causes of consciousness impairment, and that the size of the training set is more important than homogeneity of ACI etiology.

Sonography of the optic nerve sheath diameter before and after microsurgical closure of a dural CSF fistula in patients with spontaneous intracranial hypotension - a consecutive cohort study.

OBJECTIVE: Spontaneous intracranial hypotension is caused by spinal cerebrospinal fluid leakage. Patients with orthostatic headaches and cerebrospinal fluid leakage show a decrease in optic nerve sheath diameter upon movement from supine to upright position. We hypothesized that the decrease in optic nerve sheath diameter upon gravitational challenge would cease after closure of the leak. METHODS: We included 29 patients with spontaneous intracranial hypotension and refractory symptoms admitted from 2013 to 2016. The systematic workup included: Optic nerve sheath diameter sonography, spinal MRI and dynamic myelography with subsequent CT. Microsurgical sealing of the cerebrospinal fluid leak was the aim in all cases. RESULTS: Of 29 patients with a proven cerebrospinal fluid leak, one declined surgery. A single patient was lost to follow-up. In 27 cases, the cerebrospinal fluid leak was successfully sealed by microsurgery. The width of the optic nerve sheath diameter in supine position increased from 5.08 ± 0.66 mm before to 5.36 ± 0.53 mm after surgery ( p = 0.03). Comparing the response of the optic nerve sheath diameter to gravitational challenge, there was a significant change from before (-0.36 ± 0.32 mm) to after surgery (0.00 ± 0.19 mm, p < 0.01). In parallel, spontaneous intracranial hypotension-related symptoms resolved in 26, decreased in one and persisted in a single patient despite recovery of gait. CONCLUSIONS: The sonographic assessment of the optic nerve sheath diameter with gravitational challenge can distinguish open from closed spinal cerebrospinal fluid fistulas in spontaneous intracranial hypotension patients. A response to the gravitational challenge, that is, no more collapse of the optic nerve sheath while standing up, can be seen after successful treatment and correlates with the resolution of clinical symptoms. Sonography of the optic nerve sheath diameter may be utilized for non-invasive follow-up in spontaneous intracranial hypotension.