Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown ...of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we use a similar indirect disconnection approach to study a group of patients with motor deficits without anosognosia (hemiparesis or hemiplegia, HP,
= 35), or motor deficits with AHP (
= 28). The HP lesions came from a database of stroke patients, while cases of AHP were selected from the published literature. Lesions were traced into an atlas from illustrations of the publications using a standard method. There was no region in the brain that was more damaged in AHP than HP. In terms of structural connectivity, AHP patients had a similar pattern of disconnection of motor pathways to HP patients. However, AHP patients also showed significant disconnection of the right temporo-parietal junction, right insula, right lateral and medial prefrontal cortex. These associative cortical regions were connected through several white matter tracts, including superior longitudinal fasciculus III, arcuate, fronto-insular, frontal inferior longitudinal, and frontal aslant. These tracts connected regions of different cognitive networks: default, ventral attention, and cingulo-opercular. These results were not controlled for clinical variables as concomitant symptoms and other disorders of body representation were not always available for co-variate analysis. In conclusion, we confirm recent studies of disconnection demonstrating that AHP is not limited to dysfunction of motor systems, but involves a much wider set of large-scale cortical networks.
•Focal lesions like stroke and tumors cause highly-impacting cognitive impairment.•Pathophysiological mechanism (acute vs low-growing) affects differently the brain.•Focal lesions show a ...low-dimensional characterization of cognitive impairment.•Lesion location is correlated with cognitive deficits only in stroke, not in tumor.
Neuropsychological studies infer brain-behavior relationships from focal lesions like stroke and tumors. However, these pathologies impair brain function through different mechanisms even when they occur at the same brain’s location. The aim of this study was to compare the profile of cognitive impairment in patients with brain tumors vs. stroke and examine the correlation with lesion location in each pathology.
Patients with first time stroke (n = 77) or newly diagnosed brain tumors (n = 76) were assessed with a neuropsychological battery. Their lesions were mapped with MRI scans. Test scores were analyzed using principal component analysis (PCA) to measure their correlation, and logistic regression to examine differences between pathologies. Next, with ridge regression we examined whether lesion features (location, volume) were associated with behavioral performance.
The PCA showed a similar cognitive impairment profile in tumors and strokes with three principal components (PCs) accounting for about half of the individual variance. PC1 loaded on language, verbal memory, and executive/working memory; PC2 loaded on general performance, visuo-spatial attention and memory, and executive functions; and, PC3 loaded on calculation, reading and visuo-spatial attention. The average lesion distribution was different, and lesion location was correlated with cognitive deficits only in stroke. Logistic regression found language and calculation more affected in stroke, and verbal memory and verbal fluency more affected in tumors.
A similar low dimensional set of behavioral impairments was found both in stroke and brain tumors, even though each pathology caused some specific deficits in different domains. The lesion distribution was different for stroke and tumors and correlated with behavioral impairment only in stroke.
The Oxford Cognitive Screen (OCS) was developed to measure cognitive impairment in stroke. Here, we test if the OCS administered acutely in stroke patients provides useful information in predicting ...long-term functional outcome. A group of first-time stroke patients (n = 74) underwent an acute behavioral assessment comprising the OCS and the NIHSS within one-week post-stroke. Functional outcome was evaluated using the Stroke Impact Scale 3.0 (SIS 3.0) and the Geriatric Depression Scale (GDS) at 6 and 12-months post-stroke. We compared the predictive ability of the OCS and NIHSS, separately or in combination, to predict different domains of behavioral impairment at a chronic evaluation. The OCS accounted for 61% of variance of SIS physical domain, 61% of memory domain, 79% of language domain, 70% of participation domain and 70% of recovery domain. The OCS accounted for a greater percentage of outcome variance than demographics and NIHSS. The most informative predictive model included the combination of demographics, OCS and NIHSS data. The OCS, performed early after stroke, is a strong independent predictor of long-term functional outcome and significantly improves the prediction of outcome when considered alongside the NIHSS and demographics.
Objective
We conducted a multisite, randomized, double‐blinded, controlled trial to examine the effectiveness of a digital health intervention targeting the intrinsic regulation of goal‐directed ...alertness in patients with chronic hemispatial neglect.
Methods
Forty‐nine participants with hemispatial neglect, who demonstrated significant spatially biased attention after acquired brain injury, were randomly assigned to the experimental attention remediation treatment or the active control group. The participants engaged with the remotely administered interventions for 12 weeks. The primary outcome was spatial bias on the Posner cueing task (response time difference: left minus right target trials). Secondary outcomes included functional abilities (measured via the Catherine Bergego scale and Barthel index), spatial cognition, executive function, quality of life, and sleep. Assessments were conducted before and immediately after participation in the experimental intervention or control condition, and again after a 3‐month no‐contact period.
Results
Compared with the active control group, the intervention group exhibited a significant improvement in the primary outcome, a reduction in spatially biased attention on the Posner cueing task (p = 0.010, Cohen's d = 0.96), in addition to significant improvements in functional abilities as measured on the Catherine Bergego and Barthel indices (p = 0.027, Cohen's d = 0.24).
Interpretation
Our results demonstrate that our attention training program was effective in improving the debilitating attention deficits common to hemispatial neglect. This benefit generalized to improvements in real‐world functional abilities. This safe, highly scalable, and self‐administered treatment for hemispatial neglect might serve as a useful addition to the existing standard of care. ANN NEUROL 2020;88:747–758
Abstract
Neurological deficits following stroke are traditionally described as syndromes related to damage of a specific area or vascular territory. Recent studies indicate that, at the population ...level, post-stroke neurological impairments cluster in three sets of correlated deficits across different behavioural domains. To examine the reproducibility and specificity of this structure, we prospectively studied first-time stroke patients (n = 237) using a bedside, clinically applicable, neuropsychological assessment and compared the behavioural and anatomical results with those obtained from a different prospective cohort studied with an extensive neuropsychological battery. The behavioural assessment at 1-week post-stroke included the Oxford Cognitive Screen and the National Institutes of Health Stroke Scale. A principal component analysis was used to reduce variables and describe behavioural variance across patients. Lesions were manually segmented on structural scans. The relationship between anatomy and behaviour was analysed using multivariate regression models. Three principal components explained ≈50% of the behavioural variance across subjects. PC1 loaded on language, calculation, praxis, right side neglect and memory deficits; PC2 loaded on left motor, visual and spatial neglect deficits; PC3 loaded on right motor deficits. These components matched those obtained with a more extensive battery. The underlying lesion anatomy was also similar. Neurological deficits following stroke are correlated in a low-dimensional structure of impairment, related neither to the damage of a specific area or vascular territory. Rather they reflect widespread network impairment caused by focal lesions. These factors showed consistency across different populations, neurobehavioural batteries and, most importantly, can be described using a combination of clinically applicable batteries (National Institutes of Health Stroke Scale and Oxford Cognitive Screen). They represent robust behavioural biomarkers for future stroke population studies.
Neurological deficits following stroke are traditionally described as syndromes related to damage of a specific area or vascular territory. Bisogno et al. show that post-stroke neurological impairment can be described by robust, reproducible components of correlated deficits across functional domains with a bedside, clinically suitable, neurobehavioural assessment.
Graphical Abstract
Graphical Abstract
Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a disease characterised by upper airway obstruction during sleep, quite frequent in the general population, even if underestimated. Snoring, ...sleep apnoea and diurnal hypersomnia are common in these patients. Central obesity plays a key role: it reduces the size and changes the conformation of the upper airways, besides preventing lung expansion, with consequent reduction of lung volumes. Furthermore, obese people are also resistant to leptin, which physiologically stimulates ventilation; as a result, this causes scarce awakening during apnoea. OSAHS diagnosis is based on the combination of clinical parameters, such as apnoea/hypopnoea index (AHI), medical history, physical examination and Mallampati score. The first objective reference method to identify OSAHS is polysomnography followed by sleep endoscopy. Therapy provides in the first instance reduction of body weight, followed by continuous positive airway pressure (CPAP), which still remains the treatment of choice in most patients, mandibular advancement devices (MAD) and finally otolaryngology or maxillofacial surgery. Among surgical techniques, central is barbed reposition pharyngoplasty (BRP), used in the field of multilevel surgery.
Objective
To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma.
...Material and methods
We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European
paediatric
Soft tissue sarcoma Study Group (E
p
SSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted.
Results
Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval CI: 1.1–1.2) (all ADC expressed in * 10
−3
mm
2
/s), versus 1.6 (1.5–1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7–0.9) at diagnosis and 1.1 (1.0–1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3–0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 0.6–3.2) between the mean ADC change and event-free survival.
Conclusion
A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients.
Graphical Abstract
On the 27th of October 2017 the National Center for Rare Diseases of the Italian National Health Institute (NHI), clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, ...Paediatric Hospital "Bambino Gesù", Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis renewed the agreement about FC data flow for a 3 years period. The possibility to access data by third parties is among the most important new introduced within the agreement.
Aim of the present report is to improve the know-how on cystic fibrosis (CF) through a better characterization of Italian patients. Furthermore, the present Report aims at improving the care of CF patient. In particular, the Report should contribute to the following objectives: * to analize medium- and long-term clinical and epidemiological trends of the disesase; * to identify the main health care needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources; * to compare Italian data with international ones.
Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centers for Cystic Fibrosis in the period 2015-2016. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica). Data underwent to a double quality control (QC): the first by NHI and the second at a European level (before the inclusion of the italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their consistency with European core data. Finally, in 2017, an additional CQ was performed to further reduce the number of missing data and consequently improve the precision and the consistency in the nomenclature adopted for genetic mutations.
A total of 29 different CF Centres (referral, support, and Paediatric Hospital "Bambino Gesù") sent their data referred to 2015-2016 years to ICFR . Data regarding Sardinia (Southern Italy) are missing and those from Treviso (Veneto Region, Northern Italy) and Rovereto (Trentino-Alto Adige Region, Northern Italy) are sent through Verona CF Centre.
The present Report has been organized into 10 sections. 1. Demography: estimated CF patients is 5,204 in 2015 and 5,362 in 2016; median age is 20.6 and 21.0, respectively. Prevalence is 8.6/100,000 residents in Italy in 2015 and 8.8 in 2016. Male percentage is 51.6% on average for 2015 and 2016; CF distribution showed higher frequency in patients aged from 7 to 35 years. The mean of patients aged more than 18 years is 56.5% on average in 2015 and 2016. 2. Diagnoses: most of the CF patients were diagnosed before 2 years of age (median value: 68%); a significant percentage of patients (median value: 13%) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 169 in 2015 and 153 in 2016. Estimated incidence in 2015 was 1/4,176 living births in 2015 and 1/5,510 in 2016. 4. Genetics: 99.5% of patients underwent genetic analyses and in 96% of patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. delta508F was the most frequent mutation (44,7% in 2016). Furthermore, 16.0% and 3.4% of patients was characterized by the presence of at least one "residual function" mutation and gating, respectively. Finally, 21% of patients was a stop codons (class 1 mutation) carrier. 5. Lung function: FEV1 (forced expiratory volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. FEV1% values in patients between 6 and 17 years of age is ≥70%; patients with a FEV1% value of 40% are less than 2% in the period 2015-2016. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years is constant in 2015-2016 and is always more than the prevalence observed in female. An increasing percentage of female patient with a suboptimal BMI value (35.5%) is observed among patients aged more than 18 years 7.
it was estimated that, in 2016, hepatopathies without cirrhosis (17.7%) is the principal complications in patients aged less than 18 years; in patients aged more than 18 years the principal complication was due to hepatopathies without cirrhosis (29.5%) and diabetes (23.3%). 8. Transplantation: in 2015-2016, 74 patients were bipulmunary transplanted; age was comprised between 8 and 52 years, median age at transplantation was 29,6 years. Median waiting times for transplantation is estimated in 17 months (24 months in 2015 and 14 months in 2016). 9. Microbiology: analyses were referred to test performed in 2016. Percentage of adult patients with chronic Pseudomonas aeruginosa infection is 52.1% compared to 15.2% of paediatric patients; Staphylococcus aureus infection is present in 53.2% of adult patients and 52.8% of paediatric ones; Burkholderia Cepacia complex is present almost exclusively in adult patients (4.3%); Nontuberculous mycobacteria is present in 1.2% and 0.4% of adult and paediatric patients, respectively; Stenotrophomonas maltophilia infection is present in the 6.1% of adult patients and 4.9 of paediatric patients. 10. Mortality: 102 patients (49 males and 53 females; median age 36.9 years in 2015 and 36.5 in 2016) died in 2015-2016 (transplanted patients are not included).
The present Report shows that Italian CF population is growing (median age) and paediatric mortality is decreasing. A very low percentage of paediatric population is characterized by complication of pulmonary function; adult patients are characterized by an increase of age at death (more than 36 years of age in 2016).
One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic ...interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.
The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.
The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.
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