Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Racial residential segregation shapes the relationship between early childhood lead exposure and fourth-grade standardized test scores.

Racial/ethnic disparities in academic performance may result from a confluence of adverse exposures that arise from structural racism and accrue to specific subpopulations. This study investigates childhood lead exposure, racial residential segregation, and early educational outcomes. Geocoded North Carolina birth data is linked to blood lead surveillance data and fourth-grade standardized test scores (n = 25,699). We constructed a census tract-level measure of racial isolation (RI) of the non-Hispanic Black (NHB) population. We fit generalized additive models of reading and mathematics test scores regressed on individual-level blood lead level (BLL) and neighborhood RI of NHB (RINHB). Models included an interaction term between BLL and RINHB. BLL and RINHB were associated with lower reading scores; among NHB children, an interaction was observed between BLL and RINHB. Reading scores for NHB children with BLLs of 1 to 3 µg/dL were similar across the range of RINHB values. For NHB children with BLLs of 4 µg/dL, reading scores were similar to those of NHB children with BLLs of 1 to 3 µg/dL at lower RINHB values (less racial isolation/segregation). At higher RINHB levels (greater racial isolation/segregation), children with BLLs of 4 µg/dL had lower reading scores than children with BLLs of 1 to 3 µg/dL. This pattern becomes more marked at higher BLLs. Higher BLL was associated with lower mathematics test scores among NHB and non-Hispanic White (NHW) children, but there was no evidence of an interaction. In conclusion, NHB children with high BLLs residing in high RINHB neighborhoods had worse reading scores.

Premorbid personality traits as predictors for incident predementia syndromes: a multistate model approach.

OBJECTIVE: Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. METHODS: Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. RESULTS: Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. CONCLUSIONS: FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

Cognitive outcomes in anti-LGI-1 encephalitis.

OBJECTIVE: Cognitive impairment is one of the most common symptoms of anti-leucine rich glioma inactivated 1 (anti-LGI-1) encephalitis, but little is known about the cognitive profile of these patients. This study characterized the cognitive profile of patients with anti-LGI-1 encephalitis and compared patterns of impairment to healthy controls and other patient groups with known temporal lobe/limbic involvement. METHODS: A retrospective analysis of adult patients with anti-LGI-1 encephalitis who underwent neuropsychological assessment was conducted. Performance patterns of anti-LGI-1 patients were compared to patients deemed cognitively healthy (HC), as well as patients with amnestic mild cognitive impairment (aMCI) and temporal lobe epilepsy (TLE). RESULTS: Among 10 anti-LGI encephalitis patients (60% male, median age 67.5 years) who underwent neuropsychological testing (median = 38.5 months from symptom onset), cognitive deficits were common, with 100% of patients showing impairment (≤1.5 SD below mean) on 1+ measures and 80% on 2+ measures. Patients with anti-LGI-1 encephalitis performed worse than controls on measures of basic attention, vigilance, psychomotor speed, complex figure copy, and aspects of learning/memory. Of measures which differed from controls, there were no differences between the anti-LGI-1 and TLE patients, while the anti-LGI-1 patients exhibited higher rates of impairment in basic attention and lower rates of delayed verbal memory impairment compared to the aMCI patients. CONCLUSIONS: Long-term cognitive deficits are common in patients with anti-LGI-1 encephalitis and involve multiple domains. Future research in larger samples is needed to confirm these findings.

Cognitive and psychological outcomes and follow-up in severely affected COVID-19 survivors admitted to a rehabilitation hospital.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents the most recent severe pandemic resulting in coronavirus disease 2019 (COVID-19). COVID-19 can damage the central nervous system, requiring admission to intensive care units (ICU) and aggressive treatments (long-term ventilatory assistance and sedation) to stabilize vitals. Most post-COVID-19 patients experience cognitive impairments and mood or stress disorders. We aimed to study the frequency of cognitive deficits in COVID-19 survivors, the relationship between clinical factors in the acute phase and cognitive outcomes, affective states, and quality of life. We explored cognitive reserve (CR) role, as a post-COVID-19 resilience factor. METHODS: Twenty-nine COVID-19 inpatients were assessed using a neuropsychological battery, mood scales, quality of life, and social integration questionnaires. Twenty-five were retained through telephone follow-up to monitor cognitive sequelae, affective states, and reintegration levels roughly 8 months after hospital discharge. We administered the Cognitive Reserve Index questionnaire. RESULTS: We found most patients display no cognitive deficits. When they did, multi-domain impairment occurred most frequently, especially involving executive functions. Results revealed a significant correlation between depression levels and the interval between ICU admission and tracheal tube removal. We found increased levels of depression and anxiety at follow-up, a significant relationship between resuming daily life activities, high CR, and executive functions. CONCLUSIONS: These findings suggest the importance of psychological support in the long term and the modulating role of cognitive reserve in quality of life after infection.

Thirteen-Year Outcomes of a Randomized Clinical Trial of Early Preventive Care for Very Preterm Infants and Their Parents.

OBJECTIVE: To evaluate 13-year outcomes of a randomized controlled trial of preventive care (VIBeS Plus) for infants born very preterm and their parents and examine whether possible effects of intervention varied by family social risk. STUDY DESIGN: Families were randomized to an intervention arm (n = 61) or a standard care arm (n = 59). The intervention was delivered at home by psychologists and physiotherapists over the infants' first year, focusing on infant development and parental mental health. At 13 years corrected age, cognitive, motor, and behavioral outcomes, and parental mental health were assessed. Primary estimands were between-group mean differences, estimated using multiple imputed regression models. RESULTS: Follow-up included 81 surviving children (69%). There was little evidence of benefits of the intervention for IQ, attention, executive functioning, working memory, and academic skills regardless of level of social risk. Specifically, mean differences in adolescent cognitive outcomes ranged from -2.0 units (95% CI, -9.9 to 5.9) in favor of standard treatment to 5.1 units (95% CI, -2.3 to 12.5) favoring the intervention. A group-by-social risk interaction was observed only for adolescent motor outcomes, with mean differences favoring the intervention for those at higher social risk (balance, 4.9; 95% CI, 1.3-8.5; total motor, 3.2; 95% CI, 0.3-6.2), but not those at lower social risk (balance, -0.3; 95% CI, -2.4 to 1.9; total motor, 0.03; 95% CI, -1.9 to 2.0). Mean differences in adolescent behavior and parental mental health ranged from -6.6 (95% CI -13.8, 0.5) to -0.2 (95% CI, -1.9 to 1.4) and -1.8 (95% CI, -4.1 to 0.6) to -1.7 (95% CI, -4.3 to 1.0), respectively, indicating a pattern of fewer symptoms in the intervention group. CONCLUSIONS: Benefits of the intervention persisted for adolescent behavior, with better motor outcomes observed in those from socially disadvantaged families. Replication with larger samples, multiple informant reports, and assessment of quality of life-related outcomes is warranted. TRIAL REGISTRATION: http://www.anzctr.org.au/: ACTRN12605000492651.

Psychometric deficits in autoimmune encephalitis: A retrospective study from the Australian Autoimmune Encephalitis Consortium.

BACKGROUND AND PURPOSE: Despite the rapid increase in research examining outcomes in autoimmune encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. The current study aimed to characterise psychometric outcomes in this population, and explore variables that may predict psychometric outcomes. METHODS: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolitan hospitals in Victoria, Australia between January 2008 and July 2019. Frequency and pattern analysis were employed to define and characterize psychometric outcomes. Univariable logistic regression was performed to examine predictors of intact and pathological psychometric outcomes. RESULTS: Deficits in psychometric markers of executive dysfunction were the most common finding in this cohort, followed by deficits on tasks sensitive to memory. A total of 54.2% of patients were classified as having psychometric impairments across at least two cognitive domains. Twenty-nine patterns were observed, suggesting outcomes in AE are complex. None of the demographic data, clinical features or auxiliary examination variables were predictors of psychometric outcome. CONCLUSIONS: Cognitive outcomes in AE are complex. Further detailed and standardized cognitive testing, in combination with magnetic resonance imaging volumetrics and serum/cerebrospinal fluid biomarkers, is required to provide rigorous assessments of disease outcomes.

Mother knows best or does she? Perceptions of the memory abilities of pediatric patients with epilepsy as reported by patients and their parents across time.

PURPOSE: This study compared the self-reported and parent-reported memory of children with epilepsy across time and explored the relationships between these measures of subjective memory and the children's actual performance on objective neuropsychological tests. METHOD: One-hundred and nineteen children with epilepsy who were surgical candidates underwent comprehensive neuropsychological testing that included the Everyday Verbal Memory Questionnaire (EVMQ). Each child's parent and 82 of the children themselves completed the appropriate version of this subjective memory measure. After 9 months, the children returned for a second neuropsychological evaluation with 71 parents and 39 children completing the same questionnaire. Approximately one-third of the children in the study underwent surgery between the two evaluations. Standardized regression-based norms were used to quantify change in cognitive abilities across assessments. RESULTS: Results revealed significant relationships between parent reports and child reports of the children's memory abilities. Parent reports, but not child reports, correlated with the children's objective test scores at baseline. In contrast, children were more attuned to changes in their memory across time. CONCLUSIONS: These findings demonstrate the importance of considering both parent and child perceptions of everyday cognitive functioning when evaluating cognition and cognitive changes over time in pediatric patients with epilepsy.

Associations between sleep deficit and academic achievement - triangulation across time and subject domains among students and teachers in TIMSS in Norway.

BACKGROUND: Sufficient sleep is important to an individual's health and well-being, but also for school achievement among adolescents. This study investigates the associations between sleepiness, sleep deficits, and school achievements among adolescents. METHODS: This trend study involved a representative sample of Norwegian adolescents based on the "Trends in International Mathematics and Science Study" (TIMSS), N = 4499 (2015) and N = 4685 (2019) and their teachers. The students were 9th graders from a Norwegian compulsory secondary school. The survey included questions on students' sleepiness as students reported in 2019 and sleep deficits among students that limited teaching in class as their teachers reported in 2015 and 2019. Regression, triangulation, and mediation analyses were used. Mplus was used to perform the statistical analyses. RESULTS: The results revealed significant negative associations between sleep deficits and school achievements, adjusted for gender, socioeconomic status (SES), and minority status among Norwegian 9th graders. These results were found for both mathematics and science achievements in 2015 and 2019. Sleepiness that the students reported was negatively associated with school achievements in 2019. Trend and mediation analyses showed that sleep deficits explained 18 and 11% of the decrease in mathematics and science achievements, respectively, from 2015 to 2019. CONCLUSIONS: Sleep deficits were associated with school achievements in mathematics and science among Norwegian 9th graders. Mediation analyses revealed that sleep deficits explained a significant part of the decline in academic achievements. Insufficient sleep may have negative public health implications and influence adolescents' academic achievements and competences, and should therefore be discussed in both the educational and health systems.

Effect of first-month head-size growth trajectory on cognitive outcomes in preterm infants.

BACKGROUND: To examine whether the patterns of head-size growth trajectory in the first month after birth are associated with different susceptibility to cognitive impairment outcomes at age 24 months. METHODS: This retrospective cohort study included 590 infants of very-preterm survivors born between 2001 and 2016 receiving neurodevelopmental assessment at age 24 months. 403 children were enrolled for analysis after excluding infants with small-for-gestational age and severe brain injury. The head circumference (HC) growth evaluated weekly in the first month after birth compared to the at-birth HC was analyzed using group-based trajectory modeling. Neurocognition outcomes were determined as normal, borderline delay, or impaired using the Bayley Scales of Infant Development. RESULTS: The HC growth dynamics in the first month after birth showed three trajectory patterns: delayed catch-up (31.5%), slow catch-up (54.0%), and fast catch-up (14.5%), which significantly corresponded to different rates of impaired cognition at 19.5%, 6.0%, and 8.5%, respectively (p < 0.001). While 60% of the fast catch-up group had normal cognition, only one-third of the delayed catch-up group showed normal cognition. Three neonatal risk factors, gestational age (p = 0.006), respiratory distress syndrome requiring surfactant therapy (p = 0.012), and hemodynamically significant patent ductus arteriosus requiring intervention (p = 0.047) significantly affected HC growth trajectory patterning that led to cognitive impairment outcomes at follow-up. CONCLUSION: Preterm infants with delayed catch-up of head-size growth in the first month of age is susceptible to cognitive impairment outcome.

Complement-Dependent Synaptic Uptake and Cognitive Decline after Stroke and Reperfusion Therapy.

Despite the success of reperfusion therapy in significantly reducing the extent of infarct expansion after stroke, the effect of revascularization on poststroke neuroinflammation and the role of anti-inflammatory strategies in postreperfusion era are yet to be explored. Here, we investigate whether the neuroinflammatory response may still contribute to neurologic deficits after reperfused stroke by using targeted complement inhibition to suppress poststroke neuroinflammation in mice with or without concurrent reperfusion therapy. Complement inhibition was achieved using B4Crry, an injury site-targeted inhibitor of C3 activation. Following embolic stroke in male C57bl/6 mice, thrombolysis using tissue-plasminogen activator (t-PA) reduced injury and improved motor deficits, but did not improve cognitive outcomes. After both reperfused and non-reperfused stroke, complement activation and opsonization of hippocampal synapses directed ongoing microglia-dependent phagocytosis of synapses for at least 30 d after stroke, leading to a loss of synaptic density that was associated with cognitive decline. B4Crry treatment, alone or in combination with tPA, limited perilesional complement deposition, reduced microgliosis and synaptic uptake, and improved cognitive outcome without affecting regenerative responses. Furthermore, complement inhibition improved the safety, efficacy, and treatment window of reperfusion therapy with t-PA by limiting hemorrhagic transformation. This work thus demonstrates that poststroke neuroinflammation contributes to hemorrhagic transformation and progression of neurodegenerative responses in the brain even following early and successful revascularization.SIGNIFICANCE STATEMENT This study addresses two major challenges facing the treatment of stroke in the era of reperfusion therapy: hemorrhagic transformation and the disconnect between successful revascularization and functional outcomes. We studied how complement-dependent neuroinflammation drives the pathophysiology behind these challenges using a translationally relevant strategy. Complement inhibition was achieved using B4Crry, an injury site-targeted inhibitor of C3 activation. Following embolic stroke, pharmacological thrombolysis limited infarct size, but did not prevent complement activation. In reperfused and non-reperfused stroke, complement activation and opsonization of hippocampal synapses resulted in synaptic phagocytosis and subsequent cognitive decline. B4Crry treatment limited perilesional complement deposition, reduced microgliosis and synaptic uptake, and improved cognitive outcomes. Complement inhibition also improved the safety, efficacy, and treatment window of thrombolytic therapy.

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study.

BACKGROUND: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. METHODS: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status.During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. RESULTS: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (ß = -2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). CONCLUSIONS: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention.

Effectiveness of cognitive interventions on cognitive outcomes of adult intensive care unit survivors: A scoping review.

BACKGROUND: Cognitive impairments have been identified as significant under-recognised negative sequelae of postintensive care syndrome. No treatment guidelines exist for cognitive interventions addressing the devastating consequences of impairments and their potential impact on outcomes of intensive care unit (ICU) survivors. AIM: The aim of the study was to identify all available cognitive interventions and measurable outcomes for the cognitive rehabilitation of adult ICU survivors, as reported in published articles. Secondary aims included to critically synthesise existing evidence in improving adult ICU survivors' cognitive outcomes after ICU discharge and to extract implications for future research. METHODS: A scoping review was conducted based on a rigorous literature search (CINAHL, Embase, MEDLINE, PubMed, SCOPUS, Cochrane Library, and Google Scholar) using predefined keywords. The protocol was based on current guidelines. Eligibility criteria included published (i) experimental and quasi-experimental studies reporting the effects of cognitive interventions on cognitive outcomes of adult critical illness survivors after hospital discharge and (ii) protocols identifying cognitive interventions with predefined cognitive outcome measures. RESULTS: Seven studies were included: three experimental studies, two quasi-experimental studies, and two published protocols. Significant heterogeneity in the type of interventions, outcome measures, and assessment tools was noted. Interventions included variations of goal management training and an integrated multidisciplinary model. The setting, delivery, and duration of interventions varied. Cognitive outcomes included variations of global cognitive function and executive function. Overall, the evidence on the effects of cognitive interventions, as compared with routine care, in improving global cognitive function is inconclusive. More evidence support exists with respect to improving executive function. CONCLUSION: Although various cognitive intervention approaches have shown some positive effects on outcomes of ICU survivors after hospital discharge, the high risk of bias and high heterogeneity across studies preclude conclusions about the most appropriate post-ICU care to rehabilitate cognitive deficits in critical care survivors. This review highlighted a number of methodological limitations that require further investigation.

Telomere length in depression and association with therapeutic response to electroconvulsive therapy and cognitive side-effects.

BACKGROUND: Electroconvulsive therapy (ECT) is the most acutely effective treatment for severe treatment-resistant depression. However, there are concerns about its cognitive side-effects and we cannot yet confidently predict who will experience these. Telomeres are DNA-protein complexes that maintain genomic integrity. In somatic cells, telomeres shorten with each cell division. Telomere length (TL) can thus provide a measure of 'biological' aging. TL appears to be reduced in depression, though results are mixed. We sought to test the following hypotheses: (1) that TL would be shorter in patients with depression compared to controls; (2) that TL would be a predictor of response to ECT; and (3) that shorter TL would predict cognitive side-effects following ECT. METHOD: We assessed TL in whole blood DNA collected from severely depressed patients (n = 100) recruited as part of the EFFECT-Dep Trial and healthy controls (n = 80) using quantitative real-time polymerase chain reaction. Mood and selected cognitive measures, including global cognition, re-orientation time, and autobiographical memory, were obtained pre-/post-ECT and from controls. RESULTS: Our results indicate that TL does not differ between patients with depression compared to controls. TL itself was not associated with mood ratings and did not predict the therapeutic response to ECT. Furthermore, shorter baseline TL is not a predictor of cognitive side-effects post-ECT. CONCLUSIONS: Overall, TL assessed by PCR does not represent a useful biomarker for predicting the therapeutic outcomes or risk for selected cognitive deficits following ECT.

Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study.

BACKGROUND: The majority of epidemiological studies concerning possible adverse effects of paracetamol (acetaminophen) in pregnancy have been focussed on childhood asthma. Initial results of a robust association have been confirmed in several studies. Recently, a few cohort studies have looked at particular neurocognitive outcomes, and several have implicated hyperactivity. OBJECTIVES: In order to confirm these findings, further information and results are required. Here, we assess whether paracetamol intake between 18 and 32 weeks gestation is associated with childhood behavioural and cognitive outcomes using a large population. METHODS: Data collected by the Avon Longitudinal Study of Parents and Children (ALSPAC) at 32 weeks gestation and referring to the period from 18 to 32 weeks, identified 43.9% of women having taken paracetamol. We used an exposome analysis first to determine the background factors associated with pregnant women taking the drug, and then allowed for those factors to assess associations with child outcomes (measured using regression analyses). RESULTS: We identified 15 variables independently associated with taking paracetamol in this time period, which were used as potential confounders. Of the 135 neurocognitive variables considered, adjusting for the likelihood of false discovery, we identified 56 outcomes for adjusted analyses. Adjustment identified 12 showing independent associations with paracetamol use at P < .05, four of which were at P < .0001 (all related to child behaviours reported by the mother at 42 and 47 months; eg conduct problems: adjusted mean score + 0.22 (95% confidence interval 0.10, 0.33)). There were few associations with behavioural or neurocognitive outcomes after age 7-8 years, whether reported by the mother or the teacher. CONCLUSIONS: If paracetamol use in mid-to-late pregnancy has an adverse effect on child neurocognitive outcome, it appears to mainly relate to the pre-school period. It is important that these results be tested using other datasets or methodologies before assuming that they are causal.

A year-long immune profile of the systemic response in acute stroke survivors.

Stroke is a leading cause of cognitive impairment and dementia, but the mechanisms that underlie post-stroke cognitive decline are not well understood. Stroke produces profound local and systemic immune responses that engage all major innate and adaptive immune compartments. However, whether the systemic immune response to stroke contributes to long-term disability remains ill-defined. We used a single-cell mass cytometry approach to comprehensively and functionally characterize the systemic immune response to stroke in longitudinal blood samples from 24 patients over the course of 1 year and correlated the immune response with changes in cognitive functioning between 90 and 365 days post-stroke. Using elastic net regularized regression modelling, we identified key elements of a robust and prolonged systemic immune response to ischaemic stroke that occurs in three phases: an acute phase (Day 2) characterized by increased signal transducer and activator of transcription 3 (STAT3) signalling responses in innate immune cell types, an intermediate phase (Day 5) characterized by increased cAMP response element-binding protein (CREB) signalling responses in adaptive immune cell types, and a late phase (Day 90) by persistent elevation of neutrophils, and immunoglobulin M+ (IgM+) B cells. By Day 365 there was no detectable difference between these samples and those from an age- and gender-matched patient cohort without stroke. When regressed against the change in the Montreal Cognitive Assessment scores between Days 90 and 365 after stroke, the acute inflammatory phase Elastic Net model correlated with post-stroke cognitive trajectories (r = -0.692, Bonferroni-corrected P = 0.039). The results demonstrate the utility of a deep immune profiling approach with mass cytometry for the identification of clinically relevant immune correlates of long-term cognitive trajectories.

Self-perceptions on cognitive versus motor disability among neurologists.

OBJECTIVE: The modified Rankin Scale is a functional outcome measure that disproportionately represents motor deficits. We hypothesize that among physicians who most commonly use the modified Rankin Scale to counsel patients on neurological treatment options, personal perception of acceptable or optimal outcome may be discordant with those described in clinical trials. METHODS: A three-question anonymous voluntary survey was emailed to academic and community practicing neurologists and board-eligible or board-certified neurology fellows inquiring about their personal perception of a better quality of life between two choices featuring clinical scenarios that would qualify as modified Rankin Scale 2 and 4 disability outcome scores. RESULTS: Sixty-nine percent of participants were 30-45 years old, 24% were 45-60 years old, and 7% were over 60 years old. Most responders were general neurologists (31.3%). The remaining responders represented multiple subspecialties including neurocritical care, vascular neurology, neurohospitalist medicine, neuromuscular neurology, neurophysiology, child neurology, neuro-oncology, headache, neuroimmunology, movement disorders, and palliative care medicine. Forty-four of 45 neurologists (97.7%) stated they would choose needing a wheelchair if still able to function at their cognitive baseline at work (p < 0.000001). One responder preferred to get around without assistance, despite new cognitive symptoms that would preclude them from working as a physician. CONCLUSIONS: The modified Rankin Scale may not adequately represent preferred outcomes among neurology specialists, particularly with respect to cognitive symptoms. Future studies are needed to characterize long-term cognitive outcomes in patients with acute stroke-related conditions.

The challenge of overcoming the language barrier for brain tumor awake surgery in migrants: a feasibility study in five patient cases.

OBJECTIVE: To assess the feasibility of awake surgery for a brain tumor in a population of non-French-speaking migrants in Paris, France. METHODS: The Lariboisière database of awake surgeries was retrospectively reviewed, from the first case in 2011 up to July 2018. Inclusion criteria were patients being migrated in France during their adulthood, patients being unable to speak neither French nor English. Clinical and radiological data were collected from the electronic medical charts. RESULTS: Five patients fulfilled inclusion criteria. Pathological diagnosis included three glioma, one meningioma, and one melanoma metastasis. The standard awake protocol of our center was followed as usual, with the additional involvement of an interpreter at each step. In the five cases, the awake procedure allowed the surgeon to tailor the resection according to functional boundaries. Resections were complete in three cases and subtotal in two cases. No neurological deficits were observed. All patients returned to their preoperative socio-professional status. CONCLUSIONS: Awake surgery for a brain tumor can be offered to migrants, in spite of the poor verbal communication between the patient and the caring staff. A team dedicated to awake surgery and including an interpreter is the key to successfully overcome the language barrier, before, during, and after the surgery.

Laser ablation for mesial temporal lobe epilepsy: Surgical and cognitive outcomes with and without mesial temporal sclerosis.

OBJECTIVES: Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique for focal epilepsy. A major appeal of LITT is that it may result in fewer cognitive deficits, especially when targeting dominant hemisphere mesial temporal lobe (MTL) epilepsy. To evaluate this, as well as to determine seizure outcomes following LITT, we evaluated the relationships between ablation volumes and surgical or cognitive outcomes in 43 consecutive patients undergoing LITT for MTL epilepsy. METHODS: All patients underwent unilateral LITT targeting mesial temporal structures. FreeSurfer software was used to derive cortical and subcortical segmentation of the brain (especially subregions of the MTL) using preoperative magnetic resonance imaging (MRI). Ablation volumes were outlined using a postablation T1-contrasted MRI. The percentages of the amygdala, hippocampus, and entorhinal cortex ablated were quantified objectively. The volumetric measures were regressed against changes in neuropsychological performance before and after surgery, RESULTS: A median of 73.7% of amygdala, 70.9% of hippocampus, and 28.3% of entorhinal cortex was ablated. Engel class I surgical outcome was obtained in 79.5% and 67.4% of the 43 patients at 6 and 20.3 months of follow-up, respectively. No significant differences in surgical outcomes were found across patient subgroups (hemispheric dominance, hippocampal sclerosis, or need for intracranial evaluation). Furthermore, no significant differences in volumes ablated were found between patients with Engel class IA vs Engel class II-IV outcomes. In patients undergoing LITT in the dominant hemisphere, a decline in verbal and narrative memory, but not in naming function was noted. SIGNIFICANCE: Seizure-free outcomes following LITT may be comparable in carefully selected patients with and without MTS, and these outcomes are comparable with outcomes following microsurgical resection. Failures may result from non-mesial components of the epileptogenic network that are not affected by LITT. Cognitive declines following MTL-LITT are modest, and principally affect memory processes.

Long-Term Cognitive Outcomes in Patients with Autoimmune Encephalitis.

BACKGROUND: A need exists to characterise the long-term cognitive outcomes in patients who recovered from autoimmune encephalitis and to identify the modifiable factors associated with improved outcomes. METHODS: We retrospectively analysed data from patients diagnosed with autoimmune encephalitis in our outpatient autoimmune encephalitis clinic over a 5-year period, where the Montreal Cognitive Assessment (MoCA) is routinely administered. RESULTS: In total, 21 patients met the inclusion criteria, of whom 52% had persistent cognitive impairment at their latest follow-up (median delay to testing=20 months, range 13-182). Visuospatial and executive abilities, language, attention, and delayed recall were predominantly affected. Patients with status epilepticus at presentation had lower total MoCA scores at their last follow-up (median total score 21, range 15-29) compared with patients without status epilepticus at presentation (median total score 27.5, range 21-30; r 2=0.366, p=0.004). Patients who experienced delays of more than 60 days from symptom onset to initiation of treatment (either immunosuppression or tumour removal) were more likely to have a MoCA score compatible with cognitive impairment at their last follow-up (r 2=0.253, p=0.0239; z-score=-2.01, p=0.044). CONCLUSIONS: Our study suggests that the MoCA may be used to evaluate cognition in recovering patients with autoimmune encephalitis. Delays to treatment shorter than 60 days and absence of status epilepticus at onset were associated with better performance on the MoCA obtained more than 1 year after symptom onset, and may predict better long-term cognitive outcomes.