Seizures in children undergoing stem cell transplantation.

BACKGROUND: Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures. PROCEDURES: We performed a retrospective study (2002-2018) of patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures. RESULTS: Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow-up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p = .010), prophylactic or therapeutic mycophenolate use (p = .043 and .046, respectively), steroid use (p = .023), selective CD45RA+ depletion (p = .002), pre-engraftment syndrome (p = .007), and chronic graft-versus-host disease (GVHD) severity (p = .030). Seizures predicted evolution to life-threatening complications and admission to intensive care (p < .001) and higher mortality (p = .023). A statistically significant association was also found between seizures and sequelae in survivors (p = .029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 [95% CI: 7.45-186.05] and 12.95 [95% CI 2.24-74.80], respectively). CONCLUSIONS: Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure.

Relationship between visuoperceptual functions and parietal structural abnormalities in temporal lobe epilepsy.

Progressive gray matter volume reductions beyond the epileptogenic area has been described in temporal lobe epilepsy. There is less evidence regarding correlations between gray and white matter volume changepres and multi-domain cognitive performance in this setting. We aimed to investigate correlations between volume changes in parietal structures and visuospatial performance in temporal lobe epilepsy patients. we performed a cross-sectional study comparing global and regional brain volume data from 34 temporal lobe epilepsy patients and 30 healthy controls. 3D T1-weighted sequences were obtained on a 3.0 T magnet, and data were analyzed using age and sex-adjusted linear regression models. Global and regional brain volumes and cortical thickness in patients were correlated with standardized visual memory, visuoperceptual, visuospatial, and visuoconstructive parameters obtained in a per-protocol neuropsychological assessment. temporal lobe epilepsy patients had smaller volume fractions of the deep gray matter structures, putamen and nucleus accumbens, and larger cerebrospinal fluid volume fraction than controls. Correlations were found between: 1) visual memory and precuneus and inferior parietal cortical thickness; 2) visuoperceptual performance and precuneus and supramarginal white matter volumes; 3) visuospatial skills and precuneus, postcentral, and inferior and superior parietal white matter volumes; 4) visuoconstructive performance and inferior parietal white matter volume. Brain volume loss is widespread in temporal lobe epilepsy. Volumetric reductions in parietal lobe structures were associated with visuoperceptual cognitive performance.

Effect of late-onset epilepsy on cognitive functioning in patients with small vessel disease.

RATIONALE: Late-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease. METHODS: Twenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors. RESULTS: Compared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found. CONCLUSION: Patients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.

Vascular risk factors as independent predictors of neurocognitive impairments in patients with late-onset epilepsy who have small-vessel disease.

RATIONALE: Late-onset epilepsy is often accompanied by underlying cerebrovascular disease and has been associated with neurocognitive deficits even dementia, but the interrelation between them remains unknown. In this study, we aimed to explore the contribution of vascular-related and epilepsy-related factors on neurocognitive outcomes in a sample of late-onset epilepsy with history of cerebral small vessel disease. METHODS: In this retrospective cross-sectional study, a comprehensive neurocognitive assessment was performed in 25 patients aged >60 years with one or more unprovoked seizures and history of small-vessel disease. Raw scores of cognitive tests were transformed in T-scores and were grouped in 6 cognitive domains. Regression models were performed to explore the contribution of vascular risk factors (diabetes mellitus, arterial hypertension, dyslipidemia, and smoking habit) and epilepsy-related factors (drug-resistance, number of antiepileptic drugs, age at epilepsy onset, and epileptic focus localization). RESULTS: Diabetes (p = 0.03) and smoking habit (p = 0.05) were the best independent factors to predict attention performance; diabetes also predicted visual memory function (p = 0.02); gender was related to verbal memory performance (p = 0.04) and speed processing (p = 0.02). Age at onset predicted that executive function (p = 0.05); age (p = 0.01) and gender (p = 0.03) were the major contributors to language performance. Epilepsy-related variables did not predict any cognitive outcomes. CONCLUSIONS: Vascular risk factors and sociodemographic characteristics were the best predictors of cognitive outcomes in a sample of late-onset epilepsy with cerebral small-vessel disease. Epilepsy did not show influence on cognitive function. Longitudinal studies are necessary to clarify the relationship between vascular risk factors and epilepsy on progression of cognitive deterioration in patients with late-onset epilepsy. This article is part of the Special Issue "Seizures & Stroke".

Double Cycling During Mechanical Ventilation: Frequency, Mechanisms, and Physiologic Implications.

OBJECTIVES: Double cycling generates larger than expected tidal volumes that contribute to lung injury. We analyzed the incidence, mechanisms, and physiologic implications of double cycling during volume- and pressure-targeted mechanical ventilation in critically ill patients. DESIGN: Prospective, observational study. SETTING: Three general ICUs in Spain. PATIENTS: Sixty-seven continuously monitored adult patients undergoing volume control-continuous mandatory ventilation with constant flow, volume control-continuous mandatory ventilation with decelerated flow, or pressure control-continuous mandatory mechanical ventilation for longer than 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 9,251 hours of mechanical ventilation corresponding to 9,694,573 breaths. Double cycling occurred in 0.6%. All patients had double cycling; however, the distribution of double cycling varied over time. The mean percentage (95% CI) of double cycling was higher in pressure control-continuous mandatory ventilation 0.54 (0.34-0.87) than in volume control-continuous mandatory ventilation with constant flow 0.27 (0.19-0.38) or volume control-continuous mandatory ventilation with decelerated flow 0.11 (0.06-0.20). Tidal volume in double-cycled breaths was higher in volume control-continuous mandatory ventilation with constant flow and volume control-continuous mandatory ventilation with decelerated flow than in pressure control-continuous mandatory ventilation. Double-cycled breaths were patient triggered in 65.4% and reverse triggered (diaphragmatic contraction stimulated by a previous passive ventilator breath) in 34.6% of cases; the difference was largest in volume control-continuous mandatory ventilation with decelerated flow (80.7% patient triggered and 19.3% reverse triggered). Peak pressure of the second stacked breath was highest in volume control-continuous mandatory ventilation with constant flow regardless of trigger type. Various physiologic factors, none mutually exclusive, were associated with double cycling. CONCLUSIONS: Double cycling is uncommon but occurs in all patients. Periods without double cycling alternate with periods with clusters of double cycling. The volume of the stacked breaths can double the set tidal volume in volume control-continuous mandatory ventilation with constant flow. Gas delivery must be tailored to neuroventilatory demand because interdependent ventilator setting-related physiologic factors can contribute to double cycling. One third of double-cycled breaths were reverse triggered, suggesting that repeated respiratory muscle activation after time-initiated ventilator breaths occurs more often than expected.

Mechanisms involved in brain dysfunction in mechanically ventilated critically ill patients: implications and therapeutics.

Critical illness may lead to significant long-term neurological morbidity and patients frequently develop neuropsychological disturbances including acute delirium or memory impairment after intensive care unit (ICU) discharge. Mechanical ventilation (MV) is a risk factor to the development of adverse neurocognitive outcomes. Patients undergoing MV for long periods present neurologic impairment with memory and cognitive alteration. Delirium is considered an acute form of brain dysfunction and its prevalence rises in mechanically ventilated patients. Delirium duration is an independent predictor of mortality, ventilation time, ICU length of stay and short- and long-term cognitive impairment in the ICU survivors. Although, neurocognitive sequelae tend to improve after hospital discharge, residual deficits persist even 6 years after ICU stay. ICU-related neurocognitive impairments occurred in many cognitive domains and are particularly pronounced with regard to memory, executive functions, attentional functions, and processing speed. These sequelae have an important impact on patients' lives and ICU survivors often require institutionalization and hospitalization. Experimental studies have served to explore the possible mechanisms or pathways involved in this lung to brain interaction. This communication can be mediated via a complex web of signaling events involving neural, inflammatory, immunologic and neuroendocrine pathways. MV can affect respiratory networks and the application of protective ventilation strategies is mandatory in order to prevent adverse effects. Therefore, strategies focused to minimize lung stretch may improve outcomes, avoiding failure of distal organ, including the brain. Long-term neurocognitive impairments experienced by critically ill survivors may be mitigated by early interventions, combining cognitive and physical therapies. Inpatient rehabilitation interventions in ICU promise to improve outcomes in critically ill patients. The cross-talk between lung and brain, involving specific pathways during critical illness deserves further efforts to evaluate, prevent and improve cognitive alterations after ICU admission, and highlights the crucial importance of tailoring MV to prevent adverse outcomes.

Gender Differences in Social Cognition: A Cross-Sectional Pilot Study of Recently Diagnosed Patients with Schizophrenia and Healthy Subjects.

OBJECTIVES: This study had 2 objectives: First, to explore the gender-related differences in emotional processing (EP) and theory of mind-both cognitive (CToM) and affective (AToM)-in patients with schizophrenia and in a control group of healthy subjects; and, second, to examine, from a gender perspective, the possible association between EP and CToM in the AToM performance. METHODS: Forty patients with schizophrenia/schizoaffective disorder were recruited and matched by gender, age and years of education with 40 healthy subjects. EP was measured by the pictures of facial affect (POFA) test. CToM was measured using first- and second-order false-belief (FB) stories. AToM was measured by the reading the mind in the eyes test (RMET). Group and gender differences in CToM were analysed using the X2 test, whereas EP and AToM were analysed using the non-parametric Mann-Whitney U Test and a general linear model. Results were adjusted by intelligence quotient and negative symptomatology. RESULTS: Patients with schizophrenia underperformed against healthy subjects in the POFA test, second-order FB, and RMET, but not in first-order FB. No significant gender differences were found. However, there was a trend showing that females outperformed males in the POFA ( P = 0.056). Group ( P < 0.001), POFA ( P < 0.001) and second-order FB ( P = 0.022) were the best factors predicting RMET performance (adjusted R2 = 0.584). CONCLUSIONS: Our results suggest that the illness is the main factor related to the deficit in social cognition, except for the basic aspects of the CToM that were unimpaired in most patients. Nevertheless, the influence of female gender in EP should not be neglected in any group. Finally, the hierarchal interaction between these domains is discussed.

Feasibility and safety of virtual-reality-based early neurocognitive stimulation in critically ill patients.

BACKGROUND: Growing evidence suggests that critical illness often results in significant long-term neurocognitive impairments in one-third of survivors. Although these neurocognitive impairments are long-lasting and devastating for survivors, rehabilitation rarely occurs during or after critical illness. Our aim is to describe an early neurocognitive stimulation intervention based on virtual reality for patients who are critically ill and to present the results of a proof-of-concept study testing the feasibility, safety, and suitability of this intervention. METHODS: Twenty critically ill adult patients undergoing or having undergone mechanical ventilation for ≥24 h received daily 20-min neurocognitive stimulation sessions when awake and alert during their ICU stay. The difficulty of the exercises included in the sessions progressively increased over successive sessions. Physiological data were recorded before, during, and after each session. Safety was assessed through heart rate, peripheral oxygen saturation, and respiratory rate. Heart rate variability analysis, an indirect measure of autonomic activity sensitive to cognitive demands, was used to assess the efficacy of the exercises in stimulating attention and working memory. RESULTS: Patients successfully completed the sessions on most days. No sessions were stopped early for safety concerns, and no adverse events occurred. Heart rate variability analysis showed that the exercises stimulated attention and working memory. Critically ill patients considered the sessions enjoyable and relaxing without being overly fatiguing. CONCLUSIONS: The results in this proof-of-concept study suggest that a virtual-reality-based neurocognitive intervention is feasible, safe, and tolerable, stimulating cognitive functions and satisfying critically ill patients. Future studies will evaluate the impact of interventions on neurocognitive outcomes. Trial registration Clinical trials.gov identifier: NCT02078206.

Muscle, functional and cognitive adaptations after flywheel resistance training in stroke patients: a pilot randomized controlled trial.

BACKGROUND: Resistance exercise (RE) improves neuromuscular function and physical performance after stroke. Yet, the effects of RE emphasizing eccentric (ECC; lengthening) actions on muscle hypertrophy and cognitive function in stroke patients are currently unknown. Thus, this study explored the effects of ECC-overload RE training on skeletal muscle size and function, and cognitive performance in individuals with stroke. METHODS: Thirty-two individuals with chronic stroke (≥6 months post-stroke) were randomly assigned into a training group (TG; n = 16) performing ECC-overload flywheel RE of the more-affected lower limb (12 weeks, 2 times/week; 4 sets of 7 maximal closed-chain knee extensions; <2 min of contractile activity per session) or a control group (CG; n = 16), maintaining daily routines. Before and after the intervention, quadriceps femoris volume, maximal force and power for each leg were assessed, and functional and dual task performance, and cognitive functions were measured. RESULTS: Quadriceps femoris volume of the more-affected leg increased by 9.4 % in TG. Muscle power of the more-affected, trained (48.2 %), and the less-affected, untrained limb (28.1 %) increased after training. TG showed enhanced balance (8.9 %), gait performance (10.6 %), dual-task performance, executive functions (working memory, verbal fluency tasks), attention, and speed of information processing. CG showed no changes. CONCLUSION: ECC-overload flywheel resistance exercise comprising 4 min of contractile activity per week offers a powerful aid to regain muscle mass and function, and functional performance in individuals with stroke. While the current intervention improved cognitive functions, the cause-effect relationship, if any, with the concomitant neuromuscular adaptations remains to be explored. TRIAL REGISTRATION: Clinical Trials NCT02120846.

Moderate Peep After Tracheal Lipopolysaccharide Instillation Prevents Inflammation and Modifies the Pattern of Brain Neuronal Activation.

BACKGROUND: Ventilatory strategy and specifically positive end-expiratory pressure (PEEP) can modulate the inflammatory response and pulmonary-to-systemic translocation of lipopolysaccharide (LPS). Both inflammation and ventilatory pattern may modify brain activation, possibly worsening the patient's outcome and resulting in cognitive sequelae. METHODS: We prospectively studied Sprague-Dawley rats randomly assigned to undergo 3 h mechanical ventilation with 7 mL/kg tidal ventilation and either 2 cmH2O or 7 cmH2O PEEP after intratracheal instillation of LPS or saline. Healthy nonventilated rats served as baseline. We analyzed lung mechanics, gas exchange, lung and plasma cytokine levels, lung apoptotic cells, and lung neutrophil infiltration. To evaluate brain neuronal activation, we counted c-Fos immunopositive cells in the retrosplenial cortex (RS), thalamus, supraoptic nucleus (SON), nucleus of the solitary tract (NTS), paraventricular nucleus (PVN), and central amygdala (CeA). RESULTS: LPS increased lung neutrophilic infiltration, lung and systemic MCP-1 levels, and neuronal activation in the CeA and NTS. LPS-instilled rats receiving 7 cmH2O PEEP had less lung and systemic inflammation and more c-Fos-immunopositive cells in the RS, SON, and thalamus than those receiving 2 cmH2O PEEP. Applying 7 cmH2O PEEP increased neuronal activation in the CeA and NTS in saline-instilled rats, but not in LPS-instilled rats. CONCLUSIONS: Moderate PEEP prevented lung and systemic inflammation secondary to intratracheal LPS instillation. PEEP also modified the neuronal activation pattern in the RS, SON, and thalamus. The relevance of these differential brain c-Fos expression patterns in neurocognitive outcomes should be explored.

A new computerized cognitive and social cognition training specifically designed for patients with schizophrenia/schizoaffective disorder in early stages of illness: A pilot study.

People with schizophrenia/schizoaffective disorders at early stages of the illness present cognitive and social cognition deficits that have a great impact in functional outcomes. Cognitive Remediation Therapy (CRT) has demonstrated consistent effect in cognitive performance, symptoms and psychosocial functioning. However, any CRT intervention or social cognition training have been specifically designed for patients in the early stages of psychosis. The aim of this pilot study is to assess the efficacy of a new computerized cognitive and social cognition program for patients with schizophrenia/schizoaffective disorder with recent diagnosis. A comprehensive assessment of clinical, social and non-social cognitive and functional measures was carried out in 53 randomized participants before and after the 4-months treatment. Significant results were observed in Spatial Span Forwards, Immediate Logical Memory and Pictures of Facial Affect (POFA) total score. None of these results were explained by medication, premorbid social functioning or psychopathological symptoms. No impact of the intervention was observed in other cognitive and social cognition outcome neither in clinical and functional outcomes. This new computerized intervention may result effective ameliorating visual attention, logical memory and emotional processing in patients in the early stages of schizophrenia/schizoaffective disorder.

Selective effect of neurocognition on different theory of mind domains in first-episode psychosis.

The aim of this study was to investigate the influence of neurocognition on affective and cognitive theory of mind (ToM) tasks in early phases of psychosis. In a cross-sectional study of 60 first-episode schizophrenia/schizoaffective disorder patients, the implication of neurocognition in first- and second-order ToM stories, Hinting Task, and Reading the Mind in the Eyes Test (RMET) was analyzed. Regression models were used, controlling for clinical symptoms and antipsychotic dose. Spatial span backward (odds ratio [OR], 0.34; p = 0.01) and intrusions in the Rey Auditory Verbal Learning Test (OR, 4.86; p = 0.04) were the best factors to predict second-order ToM failure. Trail Making Test B (B = 0.01; p = 0.04) and negative symptoms (B = 0.09; p = 0.01) predicted Hinting task performance while Block design (B = 0.1; p = 0.04) was related to RMET outcome. Executive functions and clinical symptoms were related to ToM performance in first-episode schizophrenia patients, although different patterns of relationship were observed in each ToM task.

Influence of the neuropsychological functions in theory of mind in schizophrenia: the false-belief/deception paradigm.

The aim of this study was to investigate the influence of neurocognition in a false-belief/deception theory of mind (ToM) task in a sample of patients with schizophrenia. In a cross-sectional study of 43 remitted patients, the implication of neurocognition in first- and second-order ToM stories was analyzed, controlling for clinical symptoms and duration of illness. None of the cognitive factors were associated with the first-order ToM stories. A logistic regression model with high specificity (96.3%) and sensitivity (75%) was obtained in the second-order ToM story "The Burglar," the Information subtest (odds ratio [OR], 0.783; 95% confidence interval [CI], 0.62-0.99; p = 0.04) and the Block Design subtest (OR, 0.89; 95% CI, 0.79-1; p = 0.056) of the Wechsler Adult Intelligence Scale-III being the best predictive factors. Neurocognition was not related to first- or second-order ToM false-belief performance of the patients with schizophrenia. However, an influence of neuropsychological variables in the second-order ToM deception was observed. The clinical implications in the assessment of ToM are discussed.