Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark.

OBJECTIVES: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level. DESIGN: This was a nationwide register-based cohort study. SETTING: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System. PARTICIPANTS: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study. RESULTS: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care. CONCLUSION: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date. METHODS: We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073). RESULTS: There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, p = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group (p < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group. DISCUSSION: In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.

Effect of Remote Ischemic Conditioning in Ischemic Stroke Subtypes: A Post Hoc Subgroup Analysis From the RESIST Trial.

BACKGROUND: Remote ischemic conditioning (RIC) is a simple and noninvasive procedure that has proved to be safe and feasible in numerous smaller clinical trials. Mixed results have been found in recent large randomized controlled trials. This is a post hoc subgroup analysis of the RESIST trial (Remote Ischemic Conditioning in Patients With Acute Stroke), investigating the effect of RIC in different acute ischemic stroke etiologies, and whether an effect was modified by treatment adherence. METHODS: Eligible patients were adults (aged ≥18 years), independent in activities of daily living, who had prehospital stroke symptoms with a duration of less than 4 hours. They were randomized to RIC or sham. The RIC treatment protocol consisted of 5 cycles with 5 minutes of cuff inflation alternating with 5 minutes with a deflated cuff. Acceptable treatment adherence was defined as when at least 80% of planned RIC cycles were received. The analysis was performed using the entire range (shift analysis) of the modified Rankin Scale (ordinal logistic regression). RESULTS: A total of 698 had acute ischemic stroke, 253 (36%) were women, and the median (interquartile range) age was 73 (63-80) years. Median (interquartile range) overall adherence to RIC/sham was 91% (68%-100%). In patients with a stroke due to cerebral small vessel disease, who were adherent to treatment, RIC was associated with improved functional outcome, and the odds ratio for a shift to a lower score on the modified Rankin Scale was 2.54 (1.03-6.25); P=0.042. The association remained significant after adjusting for potential confounders. No significant associations were found with other stroke etiologies, and the overall test for interaction was not statistically significant (χ2, 4.33, P=0.23). CONCLUSIONS: In patients with acute ischemic stroke due to cerebral small vessel disease, who maintained good treatment adherence, RIC was associated with improved functional outcomes at 90 days. These results should only serve as a hypothesis-generating for future trials. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777.

Outcomes Following Adherence to a Randomized Stroke Trial Protocol.

This secondary analysis of a randomized clinical trial assesses whether compliance with the study protocol is associated with a better functional outcome even among participants in the sham-control group.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

Impact of prestroke physical activity and citalopram treatment on poststroke depressive symptoms: a secondary analysis of data from the TALOS randomised controlled trial in Denmark.

OBJECTIVES: To investigate the association between prestroke physical activity and depressive symptoms up to 6 months after stroke and examine if citalopram treatment modified the association. DESIGN: A secondary analysis of data from the multicentre randomised controlled trial The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS). SETTING AND PARTICIPANTS: TALOS was conducted at multiple stroke centres in Denmark from 2013 to 2016. It enrolled 642 non-depressed patients with first-ever acute ischaemic stroke. Patients were eligible for this study if a prestroke physical activity level was assessed by the Physical Activity Scale for the Elderly (PASE). INTERVENTIONS: All patients were randomised to citalopram or placebo for 6 months. OUTCOMES: Depressive symptoms 1 and 6 months after stroke measured on the Major Depression Inventory (MDI) ranging from 0 to 50. RESULTS: A total of 625 patients were included. Median (IQR) age was 69 (60-77) years, 410 (65.6%) were men, 309 (49.4 %) received citalopram and median (IQR) prestroke PASE score was 132.5 (76-197). Higher prestroke PASE quartile, compared with the lowest PASE quartile, was associated with fewer depressive symptoms both after 1 month (mean difference third quartile -2.3 (-4.2, -0.5), p=0.013, mean difference fourth quartile -2.4 (-4.3, -0.5), p=0.015) and 6 months after stroke (mean difference third quartile -3.3 (-5.5, -1.2), p=0.002, mean difference fourth quartile -2.8 (-5.2, -0.3), p=0.027). There was no interaction between citalopram treatment and prestroke PASE score on poststroke MDI scores (p=0.86). CONCLUSIONS: A higher prestroke physical activity level was associated with fewer depressive symptoms 1 and 6 months after stroke. Citalopram treatment did not seem to modify this association. TRIAL REGISTRATION NUMBERS: NCT01937182 (ClinicalTrials.gov) and 2013-002253-30 (EUDRACT).

Effects of remote ischemic conditioning on cognitive performance: A systematic review.

The aging process leads to subtle decline in cognitive function, and in some overt dementia. Like physical activity Remote Ischemic Conditioning (RIC) may ameliorate these changes on cognitive impairment in humans. The purpose of this study was to compared the effects of single, repeated short-term and long-term treatment RIC, and analyze its effect registered as immediate vs. long-term on cognitive performance in humans. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with PROSPERO, number (CRD42021285668). A systematic review was conducted to identify relevant studies through six healthcare science databases (Cochrane, PubMed, EMBASE, EBSCO, Scopus, and Web of Science) up to December 2021. Eligibility criteria included (1) a study sample of participants aged ≥18 years, (2) post-intervention changes on cognitive performance in humans, and (3) this systematic review included only randomized controlled trials of RIC in humans. The quality of the included studies was assessed by GRADEpro tool. A total of 118 articles were initially identified, 35 of which met the inclusion criteria. Based on title/abstract, age and RIC protocol, 14 articles were included in this review: 5 studies investigated the immediate and long-term effect of a single RIC (n = 370 patients), 4 studies examined intermittent short-term RIC (n = 174 patients) and 5 studies evaluated repeated long-term RIC (n = 228 patients). A single pre-operative RIC treatment had an immediate effect that disappeared at one week. Short-term RIC showed either a positive or no effects on cognitive function. The majority of studies examining long-term RIC treatment showed improvements in cognitive performance, particularly in very old adults and older patients with cognitive impairments. Single RIC treatment did not show any persisting effect on cognition. However, repeated short term RIC showed some improvement and long-term RIC may improve cognitive performance after stroke or enhance neuropsychological tests in patients diagnosed with vascular dementia. The mixed results might be explained by different RIC treatment protocols and populations investigated.

Too risky, too large, too late, or too mild-Reasons for not treating ischemic stroke patients and the related outcomes.

Background: Despite effective treatments, many patients are still not offered reperfusion therapy for acute ischemic stroke. Methods: We present a single-center observational study on acute ischemic stroke patients, who presented as candidates for reperfusion therapy but were deemed ineligible after work-up. Reasons for non-treatment were obtained by studying patient files and subsequently grouped into "too risky" (e.g., anticoagulant use, comorbidities), "too large" (large infarct), "too late" (late presentation of stroke and wake-up strokes), or "too mild" (clinically mild/remitting symptoms). Modified Rankin scale (mRS) score was prospectively collected in all patients by a structured telephone interview. All non-treated patients with a National Institute of Health Stroke Scale (NIHSS) score of 0-5 were compared with a similar cohort that was treated. Results: Of 529 patients with acute ischemic stroke arriving as reperfusion therapy candidates, 198 (37.4%) were not treated. The majority (42%) were not treated due to admission outside the treatment window (too late) and 24% had absolute contraindications (too risky). Only 8% was excluded because their infarct was too large [median Alberta Stroke Program Early CT score 3 (2-4)]. In the "too mild" group (14%) the percentage of patients not being independent at 90 days was 30%. The adjusted odds ratio for a better outcome (lower mRS) among treated patients with NIHSS 0-5 compared with non-treated was 1.93 (95% confidence interval 1.15-3.23). Conclusion: Presenting outside the treatment window is still the most common reason for not receiving therapy. Our study suggests a benefit of thrombolysis for patients with mild symptoms.

Conditioning medicine for ischemic and hemorrhagic stroke.

Remote ischemic conditioning (RIC) is a promising safe, feasible, and inexpensive treatment for acute stroke, both ischemic and hemorrhagic. It is applied with a blood pressure cuff on the limbs and is ideal for the prehospital setting. RIC is a form of preconditioning with similarities to physical exercise. Its mechanisms of action are multiple and include improvement of collateral cerebral blood flow (CBF) and RIC acts as a "collateral therapeutic". The increased CBF is likely related to nitric oxide synthase 3 in the endothelium and more importantly in circulating blood cells like the red blood cell. The RESIST clinical trial is a 1500 subject multicenter, randomized, sham-controlled trial of RIC in the prehospital setting in Denmark and should address the questions of whether RIC is safe and effective in acute stroke and whether the effect is mediated by an effect on nitric oxide/nitrite metabolism.

Help-seeking behaviour and subsequent patient and system delays in stroke.

OBJECTIVES: Prehospital delay is the main reason why only a limited number of stroke patients receive reperfusion therapy. We aimed to investigate help-seeking behaviour in patients and bystanders after onset of stroke and subsequent patient and system delay. MATERIALS & METHODS: We conducted a cross-sectional study of 332 patients with stroke. We performed structured interviews and used data from the medical records and the Danish Stroke Registry. Primary outcomes were patient delay and system delay. RESULTS: The median patient delay was 280 min, and the median system delay was 97 min. For a patient delay of <3 h, an additional non-significant system delay of median 30 min was seen for a first contact to a general practitioner (GP), and an additional significant delay of median 490 min was seen for the small group of patients with a first contact to 'other' healthcare professionals compared to the Emergency Medical Services (EMS). For a patient delay of more than 3 h, an additional system delay of median 78 min was found when the first contact was directed to the out-of-hours primary care (OOH-PC). A total of 17% of patients were admitted to another hospital or department before arrival at the stroke centre; this resulted in a substantially prolonged system delay of a median of 431 min. CONCLUSIONS: Patient delay remains the main reason for delayed arrival at the stroke centre. Appropriate help-seeking behaviour and efficient pre-hospital triage are essential for reducing the prehospital delay and increasing the proportion of patients receiving reperfusion therapy.

Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vector-based COVID-19 vaccine.

We describe the first Danish case of presumed inflammatory and thrombotic response to vaccination with an adenoviral (ChAdOx1) vector-based COVID-19 vaccine (AZD1222). The case describes a 60-year-old woman who was admitted with intractable abdominal pain 7 days after receiving the vaccine. Computed tomography of the abdomen revealed bilateral adrenal hemorrhages. On the following day, she developed a massive right-sided ischemic stroke and magnetic resonance imaging angiography showed occlusion of the right internal carotid artery. The ischemic area was deemed too large to offer reperfusion therapy. During admission, blood tests showed a remarkable drop in platelet counts from 118,000 to 5000 per µl and a substantial increase in D-dimer. The patient died on the sixth day of hospitalization. Blood tests revealed platelet factor 4 reactive antibodies, imitating what is seen in heparin-induced thrombocytopenia. This may be a novel immune-mediated response to the vaccine.

Fibrinolysis and Remote Ischemic Conditioning: Mechanisms and Treatment Perspectives in Stroke.

Stroke is a leading cause of death and disability. Intravenous thrombolysis and mechanical thrombectomy have greatly improved outcomes in acute ischemic stroke (AIS). However, only a minority of patients receive reperfusion therapies, highlighting the need for novel neuroprotective therapies. Remote ischemic conditioning (RIC), consisting of brief, intermittent extremity occlusion and reperfusion induced with an inflatable cuff, is a potential neuroprotective therapy in acute stroke. The objective of this narrative review is to describe the effect of RIC on endogenous fibrinolysis and, from this perspective, investigate the potential of RIC in the prevention and treatment of stroke. A systematic literature search was performed in PubMed, and human studies in English were included. Seven studies had investigated the effect of RIC on fibrinolysis in humans. Long-term daily administration of RIC increased endogenous fibrinolysis, whereas a single RIC treatment did not acutely influence endogenous fibrinolysis. Fifteen studies had investigated the effect of RIC as a neuroprotective therapy in the prevention and treatment of stroke. Long-term RIC administration proved effective in reducing new cerebral vascular lesions in patients with established cerebrovascular disease. In patients with acute stroke, RIC was safe and feasible, though its clinical efficacy as a neuroprotectant is yet unproven. In conclusion, a single RIC treatment does not affect fibrinolysis in the acute phase, whereas long-term RIC administration may increase endogenous fibrinolysis. Increased endogenous fibrinolysis is unlikely to be the mediator of the acute neuroprotective effect of RIC in stroke patients, whereas it may partly explain the reduced stroke recurrence associated with long-term RIC treatment.

Prestroke Physical Activity and Poststroke Cognitive Performance.

INTRODUCTION: Physical activity (PA) is associated with a lower risk of stroke and stroke mortality as well as a favorable stroke outcome. PA may also prevent general cognitive decline. Poststroke cognitive impairment is both common and disabling, and focusing on all possible preventive measures is important. Studies on the effect of PA on poststroke cognitive performance are sparse, however. We therefore aimed to examine the association between prestroke PA and poststroke cognitive performance. METHODS: We studied the correlation between prestroke PA and poststroke cognitive performance in a prespecified analysis in The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS) trial. We used the Physical Activity Scale for the Elderly (PASE) to collect information on PA during the 7-day period before stroke. PA was quantified, and patients were stratified into quartiles based on their PASE score. Cognitive performance was measured using the Symbol Digit Modalities Test (SDMT) at 1 and 6 months and the Mini-Mental State Examination (MMSE) at 6 months. The functional outcome was assessed using the modified Rankin Scale (mRS). RESULTS: In total, 625 of 642 patients (97%) completed the PASE questionnaire. The median age was 69 (interquartile range [IQR]: 60-77), and the median PASE score was 137 (82-205). Higher prestroke PASE quartiles (2nd, 3rd, and 4th, each compared to the 1st) were independently associated with a higher SDMT score at 1 month in the both the univariable and multivariable analyses (2nd: 3.99 points, 95% confidence interval [CI]: 1.01-6.97; 3rd: 3.6, CI: 0.6-6.61; 4th: 4.1, CI: 0.95-7.24). This association remained at 6 months. PA was not statistically associated with the MMSE score or mRS. CONCLUSION: Higher prestroke PA was associated with a better cognitive performance as measured by the SDMT at 1 and 6 months poststroke. We found no significant association between prestroke PA and functional outcome. Our results are encouraging and support further investigations of PA as a protective measure against poststroke cognitive impairment.

Extracellular Vesicles in Acute Stroke Diagnostics.

There is a large unmet need for fast and reliable diagnostics in several diseases. One such disease is stroke, where the efficacy of modern reperfusion therapies is highly time-dependent. Diagnosis of stroke and treatment initiation should be performed as soon as possible, and preferably before arrival at the stroke center. In recent years, several potential blood biomarkers for stroke have been evaluated, but without success. In this review, we will go into detail on the possibility of utilizing extracellular vesicles (EVs) released into the blood as novel biomarkers for stroke diagnostics. EVs are known to reflect the immediate state of the secreting cells and to be able to cross the blood-brain barrier, thus making them attractive as diagnostic biomarkers of brain diseases. Indeed, several studies have reported EV markers that enable differentiation between stroke patients and controls and, to a lesser extent, the ability to correctly classify the different stroke types. Most of the studies rely on the use of sophisticated and time-consuming methods to quantify specific subpopulations of the nanosized EVs. As these methods cannot be easily implemented in a rapid point of care (POC) test, technical developments followed by prospective clinical studies are needed.

Understanding the seriousness of a stroke is essential for appropriate help-seeking and early arrival at a stroke centre: A cross-sectional study of stroke patients and their bystanders.

INTRODUCTION: Only a minority of patients with acute ischaemic stroke receive reperfusion treatment, primarily due to prehospital delay. We aimed to investigate predictors of a primary contact to the emergency medical services, arrival at stroke centre within 3 h of symptom onset and initiation of reperfusion therapy in patients with acute stroke. PATIENTS AND METHODS: We conducted a cross-sectional study of consecutive patients with acute ischaemic stroke, intracerebral haemorrhage or transient ischaemic attack. Structured interviews of patients and bystanders were performed and combined with clinical information from the Danish Stroke Registry. Eligible patients were aged ≥18 years and were independent in activities of daily living before the stroke. RESULTS: We included 435 patients. Presence of a bystander at symptom onset and knowledge of ≥2 core symptoms of stroke were associated with a primary emergency medical services contact. Higher stroke severity and patients or bystanders perceiving the situation as very serious were associated with a primary emergency medical services contact (ORpatients 2.10; 95% CI 1.12-3.95 and ORbystanders 22.60; 95% CI 4.98-102.67), <3 h from onset to arrival (ORpatients 3.01; 95% CI 1.46-6.21 and ORbystanders 4.44; 95% CI 1.37-14.39) and initiation of reperfusion therapy (ORpatients 3.08; 95% CI 1.23-7.75 and ORbystanders 4.70; 95% CI 1.14-19.5).Conclusion: Having a bystander, knowledge of ≥2 core symptoms and understanding that stroke is a serious event are associated with appropriate help-seeking behaviour, shorter prehospital delay and higher chance of reperfusion therapy in acute stroke patients.

Spectral and dynamic electroencephalogram abnormalities are correlated to psychometric test performance in hepatic encephalopathy.

OBJECTIVE: Alterations of the electroencephalogram (EEG) have been reported in patients with hepatic encephalopathy (HE). However, previous methods have not assessed transient phenomena in the EEG signal (dynamics) and associations to psychometric test performance have in general been poor. The aims were to quantify spectral and dynamic EEG abnormalities in patients with HE and to correlate putative findings to psychometric test performances. METHODS: Multichannel EEG (64 electrodes) was recorded in 24 cirrhotic patients with various grades of HE and 26 healthy volunteers. Spectral and dynamic EEG indices were quantified by continues wavelet analysis. In addition, the psychometric hepatic encephalopathy score (PHES), continues reaction time, and biochemical profile were assessed. RESULTS: Compared with healthy volunteers, patients had progressively slowing of the EEG (all p ≤ 0.004) (spectral EEG indices) and increased variability in the alpha [7.5-13.5 Hz] (p = 0.001) and beta bands [13.5-32 Hz] (p = 0.02) (dynamic EEG indices). In addition, anteriorization and dissociation of the basic posterior alpha rhythm, along with dissociation of frontal delta activities [1-3.5 Hz] were seen with worsening of HE. Spectral EEG indices (all frequency bands) as well as dynamic EEG indices (alpha and beta bands) were correlated to PHES scores (all p < 0.05). CONCLUSION: EEG analysis, based on continues wavelet transform, provides quantifiable information on static as well as dynamic features of the EEG in patients with HE. EEG abnormalities were correlated to psychometric test performance and may provide valuable clinical biomarkers for surveillance, prognostication and treatment of this entity.

Gastrointestinal symptoms in type-1 diabetes: is it all about brain plasticity?

BACKGROUND AND AIMS: Autonomic neuropathy seems to play a central role in the development of gastrointestinal symptoms in diabetes. In order to explore the neuronal mechanisms behind the symptoms we evaluated the brain processing of painful visceral stimuli. METHODS: Evoked brain potentials were recorded to assess the response to painful oesophageal electrical stimuli in 15 healthy volunteers and 14 type-1 diabetes patients with autonomic neuropathy and related gastrointestinal symptoms. Source reconstruction analysis (fixed Multiple Signal Classification (MUSIC) algorithm) was applied to estimate the location of the evoked electrical activity in the brain. RESULTS: The patients had increased oesophageal sensory thresholds compared to the controls (P=0.004). The latencies of the evoked brain potentials at vertex (Cz) were increased (P=0.007) and amplitudes reduced (P=0.011) in diabetics. Compared with controls the patients had a posterior shift of the electrical sources in the anterior cingulate cortex at 54 ms, and additional sources close to the posterior insula at 95 ms and in medial frontal gyrus at 184 ms. CONCLUSIONS: There is evidence of altered central processing to visceral stimulation, and both peripheral and central mechanisms seem involved. Central neuronal reorganisation may contribute to our understanding of the gastrointestinal symptoms in patients with diabetic autonomic neuropathy and this may guide development and evaluation of new treatment modalities.

Abnormal brain processing in hepatic encephalopathy: evidence of cerebral reorganization?

BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a severe and frequent complication of liver cirrhosis characterized by abnormal cerebral function. Little is known about the underlying neural mechanisms in HE and human data are sparse. Electrophysiological methods such as evoked brain potentials after somatic stimuli can be combined with inverse modeling of the underlying brain activity. Thereby, information on neuronal dynamics and brain activity can be studied in vivo. The aim of this study was to investigate the sensory brain processing in patients with HE. PATIENTS AND METHODS: Twelve patients with minimal or overt HE and 26 healthy volunteers were included in the study. Cerebral sensory processing was investigated as (i) an auditory reaction time task; (ii) visual and somatosensory evoked brain potentials, and (iii) reconstruction of the underlying brain activity. RESULTS: Somatosensory evoked potentials were reproducible (all P>0.05), whereas flash evoked potentials were not reproducible (all P<0.05). Compared with healthy volunteers, the patient group had a prolonged reaction time index (P=0.03) along with increasing prolongation of latencies of median nerve evoked potentials (P<0.03). Reconstruction of the underlying brain sources showed a lateral shift in source localization of the P45 (P<0.001) and N60 components (P=0.02). A correlation between the psychometric hepatic encephalopathy score and the dipole shift corresponding to the N60 (P=0.003) component was seen. CONCLUSION: HE patients have evidence of prolonged intracerebral nerve conduction, along with lateralization of brain activity following median nerve stimulation. This possibly represents cortical reorganization and may be important in our understanding of this condition.