Hypoparathyroidism: changes in brain structure, cognitive impairment, and reduced quality of life.

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system-including subjective feelings of confusion, a reduced ability to focus and think clearly(i.e., "brain fog"). However, the extent to which these complex symptoms relate to quantifiable changes in patients' cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires-the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of MRI images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus-and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients' cognitive functioning.

Hypoparathyroidism (HypoPT) is a disease with insufficient or no production of Parathyroid hormone (PTH) from the parathyroid glands resulting in low plasma levels of PTH and calcium. One of the reported symptoms and complications of HypoPT is low quality of life (QOL) and mild impaired cognitive function, often described as "brain fog". We have compared patients with HypoPT and healthy controls in regard to QOL, cognitive function, and brain structure. We have used QOL questionnaires, neuropsychological tests, and Magnetic resonance imaging (MRI). We found a reduced QOL and cognitive function in patients with HypoPT. Furthermore, MRI showed a difference in brain structure, with a reduced volume of the hippocampus area, especially in those reporting severe symptoms of "brain fog". Disease duration was found to be associated with the size of the thalamus. Our study suggests that there might be an association between HypoPT patients' symptoms of cognitive deficits and changes in brain structure.

Self- and proxy-reported impaired social interaction in young adults with simple congenital heart defects.

Background: Simple Congenital Heart Defects such as septal defects constitute a large proportion of Congenital Heart Defects. New research has demonstrated more co-morbidities than previously thought. In particular, co-morbidities involving neurocognitive, psychiatric, and social difficulties have been described. Neurocognitive and psychiatric morbidities affect social interaction. Social interaction is important in everyday social life (education, work life, family life). In this study, we investigated social interaction through self- and proxy-answered Social Responsiveness Scale 2 (SRS-2) in young adults with simple Congenital Heart Defects and compared their social interaction profile to healthy matched controls. Methods: We included a total of 80 patients with either atrial or ventricular septal defect (age 26.6 years) and 38 heart-healthy, age, sex, and ISCED educational matched controls (age: 25.3 years). A close relative proxy from each participant took part in the study as well. All participants answered the Social Responsiveness Scale 2 (SRS-2) (n = 225). Our primary and secondary outcomes were the SRS-2 Total score and the SRS-2 sub-scores. Results: In the Congenital Heart Defects group, 31.3% had a Total score above 60 compared to 7.9% in the control group (p = 0.005, RR = 3.96). The participants with a septal defect had a higher Total score (52.5 vs. 45.5, p = 0.004), a higher Social Cognition sub-score (55.0 vs. 47.0, p = 0.0004), and a higher Social Motivation sub-score (50.0 vs. 45.0, p = 0.003) than the heart-healthy participants. We found no difference between the two groups regarding the sub-scores of Social Awareness and Social Communication. A multiple linear regression model showed that the variable that explained most of the variation in Total Score was having a previously diagnosed psychiatric disorder. Conclusion: We found that young adults with atrial or ventricular septal defects have a fourfold increased risk of social interaction difficulties compared to heart-healthy peers. They have a social interaction profile, with difficulties in social cognition and social motivation, and preserved social awareness and social communication. Psychiatric morbidity explained most of the variation in social interaction problems. As social difficulties and psychiatric morbidities are intertwined, social interaction difficulties could be an indication of already underlying psychiatric morbidities or a risk factor for future psychiatric morbidity.

Neuropsychological outcome after cardiac arrest: results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial.

BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA. METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance. CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.

Symptom and performance validity in neuropsychological assessments of outpatients 15-30 years of age.

OBJECTIVE: It has been suggested that performance validity tests (PVTs) assess the credibility of a patient's objective test performance, symptom validity tests (SVTs) assess the credibility of a patient's subjective complaints, and that PVTs and SVTs are independent measures. The aim of this study was to test this hypothesis and investigate the associations of PVTs and SVTs with cognitive tests and self-reported measures. METHOD: Patients 15-30 years of age were consecutively recruited from a neurorehabilitation outpatient clinic. The participants completed a battery of cognitive tests and self-reporting questionnaires as well as the Test of Memory Malingering (TOMM) and the Structured Inventory of Malingered Symptomatology (SIMS). RESULTS: Forty-eight neurological patients of various etiologies were included. The TOMM (PVT) was related to cognitive tests across cognitive domains and unrelated to self-reporting measures. The SIMS (SVT) was related to other self-reported measures of perceived stress, anxiety, and depression, though also related to cognitive test of attention and processing speed. The PVT and the SVT were unrelated and hence seemed to measure two different constructs of validity. CONCLUSIONS: This study supports the definition of PVTs and SVTs as two independent measures, consequently that both should be applied routinely in neuropsychological assessments.

Altered Cerebral Microstructure in Adults With Atrial Septal Defect and Ventricular Septal Defect Repaired in Childhood.

Background Delayed brain development, brain injury, and neurodevelopmental disabilities are commonly observed in infants operated for complex congenital heart defect. Our previous findings of poorer neurodevelopmental outcomes in individuals operated for simple congenital heart defects calls for further etiological clarification. Hence, we examined the microstructural tissue composition in cerebral cortex and subcortical structures in comparison to healthy controls and whether differences were associated with neurodevelopmental outcomes. Methods and Results Adults (n=62) who underwent surgical closure of an atrial septal defect (n=33) or a ventricular septal defect (n=29) in childhood and a group of healthy, matched controls (n=38) were enrolled. Brain diffusional kurtosis imaging and neuropsychological assessment were performed. Cortical and subcortical tissue microstructure were assessed using mean kurtosis tensor and mean diffusivity and compared between groups and tested for associations with neuropsychological outcomes. Alterations in microstructural tissue composition were found in the parietal, temporal, and occipital lobes in the congenital heart defects, with distinct mean kurtosis tensor cluster-specific changes in the right visual cortex (pericalcarine gyrus, P=0.002; occipital part of fusiform and lingual gyri, P=0.019). Altered microstructural tissue composition in the subcortical structures was uncovered in atrial septal defects but not in ventricular septal defects. Associations were found between altered cerebral microstructure and social recognition and executive function. Conclusions Children operated for simple congenital heart defects demonstrated altered microstructural tissue composition in the cerebral cortex and subcortical structures during adulthood when compared with healthy peers. Alterations in cerebral microstructural tissue composition were associated with poorer neuropsychological performance. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.

Virtual Reality and Eye-Tracking Assessment, and Treatment of Unilateral Spatial Neglect: Systematic Review and Future Prospects.

Unilateral spatial neglect (USN) is a disorder characterized by the failure to report, respond to, or orient toward the contralateral side of space to a brain lesion. Current assessment methods often fail to discover milder forms, cannot differentiate between unilateral spatial neglect subtypes and lack ecological validity. There is also a need for treatment methods that target subtypes. Immersive virtual reality (VR) systems in combination with eye-tracking (ET) have the potential to overcome these shortcomings, by providing more naturalistic environments and tasks, with sensitive and detailed measures. This systematic review examines the state of the art of research on these technologies as applied in the assessment and treatment of USN. As we found no studies that combined immersive VR and ET, we reviewed these approaches individually. The review of VR included seven articles, the ET review twelve. The reviews revealed promising results. (1) All included studies found significant group-level differences for several USN measures. In addition, several studies found asymmetric behavior in VR and ET tasks for patients who did not show signs of USN in conventional tests. Particularly promising features were multitasking in complex VR environments and detailed eye-movement analysis. (2) No VR and only a few ET studies attempted to differentiate USN subtypes, although the technologies appeared appropriate. One ET study grouped USN participants using individual heatmaps, and another differentiated between subtypes on drawing tasks. Regarding (3) ecological validity, although no studies tested the prognostic validity of their assessment methods, VR and ET studies utilized naturalistic tasks and stimuli reflecting everyday situations. Technological characteristics, such as the field of view and refresh rate of the head-mounted displays, could be improved, though, to improve ecological validity. We found (4) no studies that utilized VR or ET technologies for USN treatment up until the search date of the 26th of February 2020. In conclusion, VR-ET-based systems show great potential for USN assessment. VR-ET holds great promise for treatment, for example, by monitoring behavior and adapting and tailoring to the individual person's needs and abilities. Future research should consider developing methods for individual subtypes and differential diagnostics to inform individual treatment programs.

Self- and informant-reported executive function in young adults operated for atrial or ventricular septal defects in childhood.

BACKGROUND: Adults with simple congenital heart defects (CHD) have increased risk of neurodevelopmental challenges including executive dysfunction. It is unknown if the executive dysfunction is universal or if it is driven by dysfunction in specific clinical subscales and how it might affect psychosocial aspects of everyday life. METHODS: The self-reported and informant-reported executive function of adults with an average age of 26 ± 5 (range 18-41) who underwent childhood surgery for atrial septal defects (n = 34) or ventricular septal defects (n = 32) and matched controls (n = 40) were evaluated using the Behavior Rating Inventory of Executive Functions - Adult version (BRIEF-A). RESULTS: The CHD group reported having more executive dysfunction than controls in all BRIEF-A clinical subscales (p < 0.020) and more than their informants reported on their behalf (p < 0.006). The CHD group had received three times more special teaching (44% compared to 16%) and pedagogical psychological counselling (14% compared to none) and had a three times higher occurrence of psychiatric disorders than controls (33% compared to 11%). Lower educational levels and psychiatric disorders were associated with higher BRIEF-A scores (p < 0.03). CONCLUSIONS: Adults operated for septal defects in childhood report more challenges with all aspects of the executive functions than controls and more than relatives are aware of.

Self-Rated Executive Function and Health-Related Quality of Life in Young Adults With Persistent Post-Concussion Symptoms: A Cross-Sectional Study.

OBJECTIVE: To assess self-reported executive dysfunction in young adult patients with persistent post-concussion symptoms (PCS) 2-6 months post-injury, and the association with self-reported Health-Related Quality of Life (HRQoL). METHOD: This cross-sectional study carried out in a hospital setting was a secondary analysis of data from a separate randomized trial testing the effect of a novel intervention, "Get going After concussIoN " (GAIN), for persistent PCS. Patients (18-30 years) were recruited from a clinical cohort of patients with a hospital diagnosis of concussion or referred by primary care physicians. Main measures were The Behaviour Rating Inventory of Executive Function-Adult Version providing two index scores, that is, the Metacognitive Index (MI) and the Behavioural Regulation Index (BRI), and the Quality of Life after Brain Injury-Overall Scale. RESULTS: Compared with normative data, patients had elevated scores (i.e., worse functioning) on both the MI and the BRI. In linear regression analysis, the MI score, but not the BRI score, was negatively associated with self-reported HRQoL (MI: slope = -.27, 95% confidence interval, CI [-.53, -.02], p = .03; BRI: slope = -.19, 95% CI [-.49, .13], p = .24), suggesting a positive association of subjective executive dysfunction and lower HRQoL. However, the association was attenuated after adjustment for self-reported psychological distress (MI: slope = -.09, 95% CI [-.34, .17], p = .51). CONCLUSION: Self-reported executive dysfunction is common in young adult patients with persistent PCS, but not strongly associated with decreased HRQoL after adjusting for concurrent psychological distress.

Spatial Neglect Midline Diagnostics From Virtual Reality and Eye Tracking in a Free-Viewing Environment.

Purpose: Virtual reality (VR) and eye tracking may provide detailed insights into spatial cognition. We hypothesized that virtual reality and eye tracking may be used to assess sub-types of spatial neglect in stroke patients not readily available from conventional assessments. Method: Eighteen stroke patients with spatial neglect and 16 age and gender matched healthy subjects wearing VR headsets were asked to look around freely in a symmetric 3D museum scene with three pictures. Asymmetry of performance was analyzed to reveal group-level differences and possible neglect sub-types on an individual level. Results: Four out of six VR and eye tracking measures revealed significant differences between patients and controls in this free-viewing task. Gaze-asymmetry between-pictures (including fixation time and count) and head orientation were most sensitive to spatial neglect behavior on a group level analysis. Gaze-asymmetry and head orientation each identified 10 out of 18 (56%), compared to 12 out of 18 (67%) for the best conventional test. Two neglect patients without deviant performance on conventional measures were captured by the VR and eyetracking measures. On the individual level, five stroke patients revealed deviant gaze-asymmetry within-pictures and six patients revealed deviant eye orientation in either direction that were not captured by the group-level analysis. Conclusion: This study is a first step in using VR in combination with eye tracking measures as individual differential neglect subtype diagnostics. This may pave the way for more sensitive and elaborate sub-type diagnostics of spatial neglect that may respond differently to various treatment approaches.

Hyperactivity and Inattention in Young Patients Born With an Atrial Septal or Ventricular Septal Defect.

Background: Patients with congenital heart defects have a well-established risk of neuropsychiatric comorbidities. Inattention and hyperactivity are three to four times more frequent in children with complex congenital heart defects. We have previously shown a higher burden of overall attention deficit/hyperactivity disorder (ADHD) symptoms in adults with simple congenital heart defects as well. However, it is unknown whether the higher burden of ADHD symptoms is mainly driven by hyperactivity, inattention, or both. Methods: The participants [simple congenital heart defect = 80 (26.6 years old), controls = 36 (25.3 years old)] and a close relative for each (n = 107) responded to the long version of the Conners' Adults ADHD Rating Scales questionnaire. Our primary and secondary outcomes are mean T-scores in the ADHD scores and symptom sub-scores. Results: Patients with simple congenital heart defects reported a higher mean T-score at all three DSM-IV ADHD scores (ADHD-combined: 52.8 vs. 44.9, p = 0.007, ADHD-inattention: 55.5 vs. 46.4, p = 0.002, and ADHD-hyperactivity: 49.4 vs. 44.0, p = 0.03) and in all four ADHD symptom sub-scores (inattention/memory problems: 50.3 vs. 44.2, p = 0.001, hyperactivity/restlessness: 49.7 vs. 45.9, p = 0.03, impulsivity/emotional lability: 50.0 vs. 41.3, p = 0.001, and self-esteem problems: 53.8 vs. 46.3, p = 0.003). The results were maintained after the removal of outliers (incongruent responses), albeit the hyperactivity/restlessness ADHD symptom sub-score lost significance. Self- and informant ratings differed significantly on the ADHD-inattention score for the congenital heart defect group, where informants rated the ADHD-inattention scores better than the congenital heart defect patients rated themselves. Conclusions: Patients with a simple congenital heart defect have a higher symptom burden across all ADHD scores and all symptom sub-scores. The higher burden of ADHD is driven by both inattention and hyperactivity symptoms, though the inattention symptoms seem more prominent. Close relatives were less aware of the inattention symptoms than the congenital heart defect patients themselves. Routine screening for ADHD symptoms may be warranted to facilitate adequate help and guidance as these symptoms are easily overlooked. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03871881.

Long-term neurodevelopmental effects of intraoperative blood pressure during surgical closure of a septal defect in infancy or early childhood.

BACKGROUND: Many children born with congenital heart defects are faced with cognitive deficits and psychological challenges later in life. The mechanisms behind are suggested to be multifactorial and are explained as an interplay between innate and modifiable risk factors. The aim was to assess whether there is a relationship between mean arterial pressure during surgery of a septal defect in infancy or early childhood and intelligence quotient scores in adulthood. METHODS: In a retrospective study, patients were included if they underwent surgical closure of a ventricular septal defect or an atrial septal defect in childhood between 1988 and 2002. Every patient completed an intelligence assessment upon inclusion, 14-27 years after surgery, using the Wechsler Adult Intelligence Scale Version IV. RESULTS: A total of 58 patients met the eligibility criteria and were included in the analyses. No statistically significant correlation was found between blood pressure during cardiopulmonary bypass and intelligence quotient scores in adulthood (r = 0.138; 95% CI-0.133-0.389). Although amongst patients with mean arterial pressure < 40 mmHg during cardiopulmonary bypass, intelligence quotient scores were significantly lower (91.4; 95% CI 86.9-95.9) compared to those with mean arterial pressure > 40 mmHg (99.8; 95% CI 94.7-104.9). CONCLUSIONS: Mean arterial pressure during surgery of ventricular septal defects or atrial septal defects in childhood does not correlate linearly with intelligence quotient scores in adulthood. Although there may exist a specific cut-off value at which low blood pressure becomes harmful. Larger studies are warranted in order to confirm this, as it holds the potential of partly relieving CHD patients of their cognitive deficits.

Younger age is associated with higher levels of self-reported affective and cognitive sequelae six months post-cardiac arrest.

BACKGROUND: Affective and cognitive sequelae are frequently reported in cardiac arrest survivors; however, little is known about the risk factors. We assessed the hypothesis that self-reported affective and cognitive sequelae six months after OHCA may be associated with demography, acute care and cerebral outcome. METHODS: This is a sub-study of the multicentre "Target Temperature Management for 48 vs. 24 h and Neurologic Outcome after Out-of-Hospital Cardiac Arrest: A Randomised Clinical Trial" (the TTH48 trial) investigating the effect of prolonged TTM at 33 ±â€¯1 °C. We invited patients with good outcome on the Cerebral Performances Categories (CPC score ≤ 2) to answer questionnaires on anxiety, depression, emotional distress, perceived stress and cognitive failures six months post OHCA. RESULTS: In total 79 of 111 eligible patients were included in the analysis. There were no significant differences in baseline characteristics between the included group and the group lost to follow-up. Younger age was a negative predictor across all self-reported outcomes, even when controlling for gender, ROSC time, treatment allocation, cognitive impairment and global outcome (CPC 1 or 2). Female gender was a predictor of anxiety, though this should be interpreted cautiously as only eight women participated. A CPC score of 2 score was a negative predictor of self-reported affective outcomes, albeit not for self-reported cognitive failures. CONCLUSION: Younger age was associated with higher levels of self-reported affective and cognitive sequelae six months post OHCA. Female gender may be associated with self-reported anxiety. A higher CPC score may be a proxy for self-reported affective sequelae.

Abnormal Left-Hemispheric Sulcal Patterns in Adults With Simple Congenital Heart Defects Repaired in Childhood.

Background Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnormalities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. Methods and Results Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group (P=0.033 and P=0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group. Conclusions Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding patterns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.

Biomarker prognostication of cognitive impairment may be feasible even in out-of hospital cardical arrest survivors with good neurological outcome.

BACKGROUND: Patients surviving out-of hospital cardicac arrest, with good neurological outcome according to Cerebral Performance Category, frequently have neuropsychological impairment. We studied whether biomarker data (S-100b and neuron-specific enolase) obtained during the ICU stay predicted cognitive impairment 6 months after resuscitation. METHODS: Patients (N = 79) with a CPC-score ≤2 were recruited from two trial sites taking part in the TTH48 trial comparing targeted temperature management (TTM) for 48 h vs. 24 h at 33 ± 1 °C. We assessed patients 6 months after the OHCA. We measured biomarkers S-100b and NSE at arrival and at 24, 48 and 72 h after reaching the target temperature of 33 ± 1 °C. Four cognitive domain z-scores were calculated, and global cognitive impairment was defined as z < -1.67 on at least 3 out of 13 cognitive tests. Non-parametric correlations were used to assess the relationship between cognitive domain and biomarkers. ROC curves were used to assess prediction of cognitive impairment from the biomarkers. Logistic regression was used to investigate whether TTM duration moderated biomarker prediction of cognitive impairment. RESULTS: Cognitive impairment was present in 22% of the patients with memory impairment being the most common. The biomarkers correlated significantly with several cognitive domain scores and NSE at 48 h predicted cognitive impairment with 100% sensitivity and 56% specificity. The predictive properties of NSE at 48 h was unaffected by duration of TTM. CONCLUSIONS: Early biomarker prognostication of cognitive impairment is feasible even in OHCA survivors with good neurological outcome as defined by CPC. NSE at 48 h predicted cognitive impairment.

Assessment of spatial neglect in clinical practice: A nationwide survey.

This study was part of a nationwide, anonymous, open Internet survey conducted amongst healthcare professionals in Denmark on the assessment and treatment of spatial neglect (SN). The objective was to describe knowledge and practices in the assessment of SN in current clinical practice across different healthcare sectors and professions. Data included the perceived prevalence, assessment methods and observations, subtypes and differential diagnostics of SN. A total of 525 professionals participated in the survey. The vast majority (81.5%) reported that assessment of SN was provided by their workplace. The median of perceived prevalence of SN was 35% (IQR 22-51) but major differences were found between professions. Occupational therapists and psychologists appeared to be most involved in assessment, whilst nursing staff and speech therapists were least involved. Subjective observations were the most common assessment method (90%). Conversely, systematic ADL observations, paper-and-pencil tests, confrontational tests and computerized tests were less common. The survey revealed large differences in the assessment methods and awareness of various aspects of SN symptoms (subtypes and differential diagnostics) between different healthcare professions. The results emphasize the need for international multidisciplinary clinical guidelines on how to assess SN and distinguish between different subtypes and differential diagnoses.

Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2).

BACKGROUND: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. METHODS: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. DISCUSSION: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371 . Registered 1 June 2018.

Neuropsychological Status and Structural Brain Imaging in Adults With Simple Congenital Heart Defects Closed in Childhood.

Background Neurodevelopmental impairments are common in survivors of complex congenital heart defects (CHD). We report neuropsychological and brain imaging assessments in adults operated for isolated septal defects. Methods and Results Patients (mean age 25.6 yrs) who underwent childhood surgery for isolated atrial septal defect (n=34) or ventricular septal defect (n=32), and healthy matched peers (n=40), underwent a standard battery of neuropsychological tests and a 3.0T brain magnetic resonance imaging scan. Patient intelligence was affected with lower scores on Full-Scale intelligence quotient (P<0.001), Verbal Comprehension (P<0.001), Perceptual Reasoning (P=0.007), and Working Memory (P<0.001) compared with controls. Also, the CHD group had poorer visuospatial abilities (Immediate Recall, P=0.033; Delayed Recall, P=0.018), verbal memory (Trial 1, P=0.015; Total Learning, P<0.001; Delayed Recall, P=0.007), executive function (Executive Composite Score, P<0.001), and social recognition (Reading the Mind in the Eyes Test, P=0.002) compared with controls. Self-reported levels of executive dysfunction, attention deficits and hyperactivity behavior, and social cognition dysfunction were higher in the CHD group compared with population means and controls. We found similar global and regional morphometric brain volumes and a similar frequency of brain magnetic resonance imaging abnormalities in the 2 groups. The CHD group had a high occurrence of psychiatric disease and a larger need for special teaching during school age. Conclusions Children operated for simple CHD demonstrate poorer neurodevelopmental outcomes in adulthood when compared with healthy controls and expected population means. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03871881.

Cerebellar Cognitive Affective Syndrome in Children With Acute Postinfectious Cerebellar Ataxia.

BACKGROUND: Acute postinfectious cerebellar ataxia is the most common cause of acute ataxia in childhood. One previous case study has suggested that cerebellar cognitive affective syndrome may be comorbid with acute postinfectious cerebellar ataxia, but this was not confirmed by formal assessments. METHODS: Children aged three to 15 years with a confirmed diagnosis of acute postinfectious cerebellar ataxia were invited to participate. Three patients were included and assessed by a pediatrician, neuropsychologist, and logopedist at the subacute stage (less than 14 days post-onset) and after six months and one year of follow-up. RESULTS: All three children complied with the diagnostic criteria of cerebellar cognitive affective syndrome. The cognitive and affective symptoms persisted longer than the motor symptoms. Child A (girl, aged three years and eight months) was most severely affected with slow progression of motor cerebellar symptom; the cerebellar cognitive affective symptoms had not entirely remitted at one-year follow-up. Child B (boy, aged four years and four months) had more subtle motor cerebellar symptoms that swiftly remitted within the first week; the cerebellar cognitive affective symptoms were also more subtle. Child C (boy, aged seven years and eleven months) was considerably affected by motor cerebellar symptoms but showed marked improvement within the first month; the cerebellar cognitive affective symptoms had not entirely remitted at one-year follow-up. CONCLUSION: Cognitive affective cerebellar syndrome may be an overlooked complication of acute postinfectious cerebellar ataxia. The severity of cerebellar cognitive affective symptoms seemed to correspond to the severity of the cerebellar motor symptoms, but the improvement was remarkably slower.

Treatment of spatial neglect in clinical practice: A nationwide survey.

OBJECTIVES: Clinical research has documented a range of evidence-based treatment approaches for spatial neglect (SN), but there is a lack of research on the implementation of treatment into clinical practice. The purpose of this study is to describe the current clinical practice of SN treatment across healthcare sectors including involved professions, methods, timing and sources of evidence. MATERIAL AND METHODS: This is the second part of a nationwide, anonymous, open Internet survey that was conducted among healthcare professionals in Denmark on assessment and treatment of SN. RESULTS: A total of 525 healthcare professionals participated in the survey of which 411 (78.3%) reported that SN treatment was provided at their workplace. Occupational and physiotherapist were most often involved in the treatment, most commonly characterized by training of activities of daily living (ADL), sensoric stimulation and cueing. Less frequently reported were evidence-based methods such as prism adaptation and visual scanning. The overall intensity of the SN treatment varied considerably across sectors and might consequently be inadequate. A minority of the participants consulted clinical research evidence in their choice of SN treatment approaches. CONCLUSIONS: There is a profound lack of dissemination and translation of clinical research into current clinical practice, which unarguably leads to an underuse of evidence-based treatment approaches in SN rehabilitation. The results call for international multidisciplinary clinical guidelines for the treatment of SN at different stages of rehabilitation and the tailoring of treatment approaches to the individual patient.

The Effects of High-Intensity Aerobic Exercise on Cognitive Performance After Stroke: A Pilot Randomised Controlled Trial.

BACKGROUND: Aerobic exercise is an effective treatment to improve aerobic capacity following stroke and might also improve cognitive impairments in sub-acute stroke survivors. The aim of the study was to assess the effect of high-intensity aerobic exercise on cognitive impairments in sub-acute stroke survivors. METHODS: A pilot, randomised controlled trial on the effects of aerobic exercise on cognitive impairments of stroke patients in the sub-acute (1-3 months) phase was conducted. Thirty patients with moderate cognitive impairments (maximum score of 5 on at least two items on the cognitive subscales of the Functional Independence Measure [FIM]) were included in the study and randomly assigned to either the intervention group - performing high-intensity aerobic exercise (above 70% of maximum heart rate), or the control group - performing low-intensity aerobic exercise (below 60%). Patients in both groups exercised for 50 min twice a week for 4 weeks. Primary neuropsychological outcome: Trail Making Test B. RESULTS: Thirty stroke patients completed the interventions. The results showed that the high-intensity group, compared with the low-intensity group, achieved significant improvements on Trail Making Test B, which assesses processing speed and divided attention (P = .04 after training and P = .01 at follow-up). However, the significant improvements on Trail Making Test B might relate to a ceiling effect in the control group. CONCLUSIONS: This study does not provide evidence to support that aerobic exercise can improve cognition in stroke survivors, even though significant improvement was revealed on the primary outcome in sub-acute stroke survivors following high-intensity aerobic exercise compared with low-intensity general exercise.