Case-Fatality and Functional Outcome after Subarachnoid Hemorrhage (SAH) in INternational STRoke oUtComes sTudy (INSTRUCT).

BACKGROUND: There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. METHODS: We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. RESULTS: Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. CONCLUSION: Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

Translation and Transcultural Adaptation of the Wessex Head Injury Matrix, Italian Version: A Preliminary Report.

BACKGROUND: Patients who are in a coma, a vegetative state or a minimally conscious state present a clinical challenge for neurological assessment, which is a prerequisite for establishing a prognosis and planning management. Several scales have been developed to evaluate these patients. The Wessex Head Injury Matrix is a comprehensive tool but is currently available only in the French and English languages. The aim of this study was to translate and evaluate the reliability of the Italian version of the scale. METHODS: The original scale was translated according to a standard protocol: three separate translations were made, and a selected version was back-translated to check for any errors in order to obtain the most accurate Italian translation. A final back translation of the agreed version was made as a further check. The final version was then administered blind to a consecutive series of patients with severe acquired brain injury by two examiners. Inter-rater and test-retest reliability were assessed using a weighted Cohen's kappa (Kw). Concurrent validity of the WHIM was evaluated by ρ Spearman's correlation coefficient using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale Revised (CRS-R) as the available gold standard. RESULTS: Twenty-four patients (12 males and 12 females; mean age 59.9 ± 20.1; mean duration from index event 17.7 ± 20.0 days) with stroke (n = 15), traumatic brain injury (n = 7) and anoxic encephalopathy (n = 2) were included. Inter-rater [Kw 0.80 (95% CI 0.75-0.84)] and test-retest reliability [Kw 0.77 (95% CI 0.72-0.81)] showed good values. WHIM total scores correlated significantly with total scores on the GCS (ρ = 0.776; p < 0.001) and the CRS-R (ρ = 0.881; p < 0.001) demonstrating concurrent validity; Conclusion: The Italian version of the scale is now available for clinical practice and research.

Multimodal MRI Assessment of Thalamic Structural Changes in Earthquake Survivors.

Moving from the central role of the thalamus in the integration of inner and external stimuli and in the implementation of a stress-related response, the objective of the present study was to investigate the presence of any MRI structural and volumetric changes of the thalamic structures in earthquake witnesses. Forty-one subjects were included, namely 18 university students belonging to the experimental earthquake-exposed group (8 males and 10 females, mean age 24.5 ± 1.8 years) and a control group of 23 students not living in any earthquake-affected areas at the time of the earthquake (14 males and 9 females, mean age 23.7 ± 2.0 years). Instrumental MRI evaluation was performed using a 3-Tesla scanner, by acquiring a three-dimensional fast spoiled gradient-echo (FSPGR) sequence for volumetric analysis and an EPI (echoplanar imaging) sequence to extract fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. As compared to the control one, the experimental group showed significantly lower gray matter volume in the mediodorsal nucleus of the left thalamus (p < 0.001). The dominant hemisphere thalamus in the experimental group showed higher mean ADC values and lower mean FA values as compared to the control group.

Sex Differences in Disease Profiles, Management, and Outcomes Among People with Atrial Fibrillation After Ischemic Stroke: Aggregated and Individual Participant Data Meta-Analyses.

Objectives: To examine sex differences in disease profiles, management, and survival at 1 and 5 years after ischemic stroke (IS) among people with atrial fibrillation (AF). Methods: We performed a systematic literature search of reports of AF at IS onset according to sex. We undertook an individual participant data meta-analysis (IPDMA) of nine population-based stroke incidence studies conducted in Australasia, Europe, and South America (1993-2014). Poisson regression was used to estimate women:men mortality rate ratios (MRRs). Study-specific MRRs were combined using random effects meta-analysis. Results: In our meta-analysis based on aggregated data from 101 studies, the pooled AF prevalence was 23% (95% confidence interval [CI]: 22%-25%) in women and 17% (15%-18%) in men. Our IPDMA is of 1,862 IS-AF cases, with women (79.2 ± 9.1, years) being older than men (76.5 ± 9.5, years). Crude pooled mortality rate was greater for women than for men (1-year MRR 1.24; 1.01-1.51; 5-year 1.12; 1.03-1.22). However, the sex difference was greatly attenuated after accounting for age, prestroke function, and stroke severity (1-year 1.09; 0.97-1.22; 5-year 0.98; 0.84-1.16). Women were less likely to have anticoagulant prescription at discharge (odds ratio [OR] 0.94; 95% CI: 0.89-0.98) than men when pooling IPDMA and aggregated data. Conclusions: AF was more prevalent after IS among women than among men. Among IS-AF cases, women were less likely to receive anticoagulant agents at discharge; however, greater mortality rate in women was mostly attributable to prestroke factors. Further information needs to be collected in population-based studies to understand the reasons for lower treatment of AF in women.

IER-START nomogram for prediction of three-month unfavorable outcome after thrombectomy for stroke.

BACKGROUND: The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance. AIMS: We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy <6 h of stroke onset. METHODS: We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3-6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training (n = 1219) and test (n = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816-0.869) in the training set, and 0.820 (95% CI: 0.786-0.854) in the test set. CONCLUSIONS: The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome.

The Comorbidities Coma Scale (CoCoS): Psychometric Properties and Clinical Usefulness in Patients With Disorders of Consciousness.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample (n = 162). Interrater reliability, assessed by the weighted Cohen's kappa (Kw), and concurrent validity of the scale as compared to the Greenfield Scale, assessed by ρ Spearman's correlation coefficient, were investigated in a subsample of patients (n = 52) within two of the above units. Our findings provided evidence of a good content validity of the scale, with the identification of a 12-factor structure representing the different comorbid dimensions of the target population. Inter-rater reliability was excellent in both the rehabilitation units where the assessment was made [Kw 0.98 (95% CI 0.96-0.99)]. CoCoS total scores correlated significantly with total scores of the Greenfield Scale (ρ = 0.932, 95% CI 0.89-0.96; P < 0.0001) indicating that CoCoS has concurrent validity while being more informative about the specific pattern of comorbidities of these challenging patients. The CoCos is a new tool which standardizes the approach to assessment of comorbid conditions and reliably identifies the category and severity of each comorbidity detected. It may be used for both clinical and research applications.

Neural Correlates of Facial Expression Recognition in Earthquake Witnesses.

Major adverse events, like an earthquake, trigger different kinds of emotional dysfunctions or psychiatric disorders in the exposed subjects. Recent literature has also shown that exposure to natural disasters can increase threat detection. In particular, we previously found a selective enhancement in the ability to read emotional facial expressions in L'Aquila earthquake witnesses, suggesting hypervigilance to stimuli signaling a threat. In light of previous neuroimaging data showing that trauma exposure is related to derangement of resting-state brain activity, in the present study we investigated the neurofunctional changes related to the recognition of emotional faces in L'Aquila earthquake witnesses. Specifically, we tested the relationships between accuracy in recognizing facial expressions and activity of the visual network (VN) and of the default-mode network (DMN). Resting-state functional connectivity (FC) with the main hub of the VN (primary, ventral, right-dorsal, and left-dorsal visual cortices) and DMN (posterior cingulate/precuneus, medial prefrontal, and right and left inferior parietal cortices) was investigated through a seed-based functional magnetic resonance imaging (fMRI) analysis in both earthquake-exposed subjects and non-exposed persons who did not live in an earthquake-affected area. The results showed that, in earthquake-exposed subjects, there is a significant reduction in the correlation between accuracy in recognizing facial expressions and the FC of the dorsal seed of the VN with the right inferior occipito-temporal cortex and the left lateral temporal cortex, and of two parietal seeds of DMN, i.e., lower parietal and medial prefrontal cortex, with the precuneus bilaterally. These findings suggest that a functional modification of brain systems involved in detecting and interpreting emotional faces may represent the neurophysiological basis of the specific "emotional expertise" observed in the earthquake witnesses.

Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.

BACKGROUND: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. PURPOSE: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. METHODS: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. RESULTS: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)). CONCLUSIONS: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

IER-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Thrombectomy for Stroke.

Background and Purpose- As a reliable scoring system to detect the risk of symptomatic intracerebral hemorrhage after thrombectomy for ischemic stroke is not yet available, we developed a nomogram for predicting symptomatic intracerebral hemorrhage in patients with large vessel occlusion in the anterior circulation who received bridging of thrombectomy with intravenous thrombolysis (training set), and to validate the model by using a cohort of patients treated with direct thrombectomy (test set). Methods- We conducted a cohort study on prospectively collected data from 3714 patients enrolled in the IER (Italian Registry of Endovascular Stroke Treatment in Acute Stroke). Symptomatic intracerebral hemorrhage was defined as any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline ≤24 hours or death. Based on multivariate logistic models, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve. Results- National Institutes of Health Stroke Scale score, onset-to-end procedure time, age, unsuccessful recanalization, and Careggi collateral score composed the IER-SICH nomogram. After removing Careggi collateral score from the first model, a second model including Alberta Stroke Program Early CT Score was developed. The area under the receiver operating characteristic curve of the IER-SICH nomogram was 0.778 in the training set (n=492) and 0.709 in the test set (n=399). The area under the receiver operating characteristic curve of the second model was 0.733 in the training set (n=988) and 0.685 in the test set (n=779). Conclusions- The IER-SICH nomogram is the first model developed and validated for predicting symptomatic intracerebral hemorrhage after thrombectomy. It may provide indications on early identification of patients for more or less postprocedural intensive management.

Anticoagulation After Stroke in Patients With Atrial Fibrillation.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Cognitive and Emotional Empathy in Individuals with Spinal Cord Injury.

BACKGROUND: Empathy has been conceptualized as comprising a cognitive and an emotional component, the latter being further divided into direct and indirect aspects, which refer, respectively, to the explicit evaluation of the observer's feelings while attending someone in an emotional situation and to the physiological response of the observer. Empathy has been previously investigated in several neurological disorders. OBJECTIVE: This study is aimed at investigating empathy in patients with spinal cord injury (SCI). We hypothesize that, due to deafferentation following their injury, SCI patients will display difficulty in the processing of emotional stimuli and blunted empathic responses as compared to healthy controls. MATERIALS AND METHODS: 20 patients with spinal cord injury (SCI) (12 males and 8 females, mean age = 50.9, standard deviation (SD) = 16.1 years; mean education = 10.9, SD = 4.1 years) were included in the study and compared to 20 matched healthy subjects. Participants were investigated using the State-Trait Anxiety Inventory (Form Y) (STAI-Y), the Beck Depression Scale, and the Toronto Alexithymia Scale. Moreover, participants were further evaluated by means of the Interpersonal Reactivity Index (IRI), which explores both cognitive and emotional aspects of empathy, and through an experimental protocol based on the use of a modified version of the computerized Multifaceted Empathy Test (MET) to evaluate emotional (direct and indirect) empathy and the ability to judge the valence of complex emotional scenes. RESULTS: As compared to healthy controls, SCI patients reported higher scores on the Perspective-Taking subscale of the IRI, while, on the modified MET, they were less accurate in identifying the valence of neutral scenes, notwithstanding their spared direct and indirect emotional empathy ability. Furthermore, we found a significant negative correlation between the time interval since injury and the direct emotional empathy scores on the positive images, as well as a negative correlation with the indirect emotional empathy scores on both positive and neutral images, indicating a blunting of the empathic responses as time elapses. CONCLUSION: Results suggest that SCI patients, when analyzing the meaning of emotional stimuli, tend to rely on a cognitive empathy strategy rather than on emotion simulation.

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease-study protocol and preliminary results.

BACKGROUND: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. METHODS: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. RESULTS: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. CONCLUSION: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy.

Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

Post-earthquake Distress and Development of Emotional Expertise in Young Adults.

After a natural disaster like an earthquake about 15% of the population experience a post-traumatic stress disorder (PTSD). However, even those without a diagnosis of PTSD can suffer from disorders of the affective sphere, including anxiety, depression and alteration of emotion recognition. The objective of this study was to investigate the neuropsychological and emotional profile of students living in the earthquake-affected areas of L'Aquila, Italy. A group of students living in L'Aquila at the time of the 2009 earthquake was recruited, and compared to a control group of students not living in any earthquake-affected areas. Participants were assessed by means of the Beck Depression Inventory (BDI) scale, the State-Trait Anxiety Inventory (STAI), the Insomnia Severity Index (ISI), the Intolerance of Uncertainty Scale Short Form, the Uncertainty Response Scale (URS), the Anxiety Sensitivity Index 3 (ASI-3), and the Eysenck Personality Questionnaire-Revised Short Form (EPQ-RS). Participants also took part in two behavioral experiments aimed at evaluating their ability to recognize facial expressions (by means of the Ekman and Friesen Pictures of Facial Affect) and to evaluate emotionally evocative scenes (by means of the International Affective Picture System (IAPS)). Results showed that students living in the earthquake-affected areas had a general increase of anxiety and anticipation of threats. Moreover, students living in the earthquake-affected areas showed a significantly higher overall accuracy in recognizing facial expressions as compared to controls. No significant differences between the two groups were detected in the evaluation of emotionally evocative scenes. The novel result lies in the greater accuracy of earthquake victims in recognizing facial expressions, despite the lack of differences from controls in evaluating affective evocative scenes. The trauma exposure may have increased vigilance for threats in earthquake victims, leading them to systematically pay attention to potential signs of approaching threats, such as emotional facial expressions, thus progressively developing particular "emotional expertise."

Cortical Brain Changes in Patients With Locked-In Syndrome Experiencing Hallucinations and Delusions.

Previous evidence suggests that hallucinations and delusions may be detected in patients with the most severe forms of motor disability including locked-in syndrome (LIS). However, such phenomena are rarely described in LIS and their presence may be underestimated as a result of the severe communication impairment experienced by the patients. In this study, we retrospectively reviewed the clinical history and the neuroimaging data of a cohort of patients with LIS in order to recognize the presence of hallucinations and delusions and to correlate it with the pontine damage and the presence of any cortical volumetric changes. Ten patients with LIS were included (5 men and 5 women, mean age 50.1 ± 14.6). According to the presence of indicators of symptoms, these patients were categorized as hallucinators (n = 5) or non-hallucinators (n = 5). MRI images of patients were analyzed using Freesurfer 6.0 software to evaluate volume differences between the two groups. Hallucinators showed a selective cortical volume loss involving the fusiform (p = 0.001) and the parahippocampal (p = 0.0008) gyrus and the orbital part of the inferior frontal gyrus (p = 0.001) in the right hemisphere together with the lingual (p = 0.01) and the fusiform gyrus (p = 0.01) in the left hemisphere. Moreover, a volumetric decrease of bilateral anterior portions of the precuneus was recognized in the hallucinators (right p = 0.01; left p = 0.001) as compared to non-hallucinators. We suggested that the presence of hallucinations and delusions in some LIS patients could be accounted for by the combination of a damage of the corticopontocerebellar pathways with cortical changes following the primary brainstem injury. The above areas are embedded within cortico-cortical and cortico-subcortical loops involved in self-monitoring and have been related to the presence of hallucinations in other diseases. The two main limitations of our study are the small sample of included patients and the lack of a control group of healthy individuals. Further studies would be of help to expand this field of research in order to integrate existing theories about the mechanisms underlying the generation of hallucinations and delusions in neurological patients.

Factors contributing to sex differences in functional outcomes and participation after stroke.

OBJECTIVE: To examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke. METHODS: Individual participant data on long-term functional outcome or participation restriction (i.e., handicap) were obtained from 11 stroke incidence studies (1993-2014). Multivariable log-binomial regression was used to estimate the female:male relative risk (RR) of poor functional outcome (modified Rankin Scale score >2 or Barthel Index score <20) at 1 year (10 studies, n = 4,852) and 5 years (7 studies, n = 2,226). Multivariable linear regression was used to compare the mean difference (MD) in participation restriction by use of the London Handicap Scale (range 0-100 with lower scores indicating poorer outcome) for women compared to men at 5 years (2 studies, n = 617). For each outcome, study-specific estimates adjusted for confounding factors (e.g., sociodemographics, stroke-related factors) were combined with the use of random-effects meta-analysis. RESULTS: In unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RRunadjusted 1.32, 95% confidence interval [CI] 1.18-1.48; 5 years: RRunadjusted 1.31, 95% CI 1.16-1.47). However, this difference was greatly attenuated after adjustment for age, prestroke dependency, and stroke severity (1 year: RRadjusted 1.08, 95% CI 0.97-1.20; 5 years: RRadjusted 1.05, 95% CI 0.94-1.18). Women also had greater participation restriction than men (pooled MDunadjusted -5.55, 95% CI -8.47 to -2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MDadjusted -2.48, 95% CI -4.99 to 0.03). CONCLUSIONS: Worse outcomes after stroke among women were explained mostly by age, stroke severity, and prestroke dependency, suggesting these potential targets to improve the outcomes after stroke in women.