Early effect of dalfampridine in patients with MS: A multi-instrumental approach to better investigate responsiveness.

BACKGROUND: 4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed. OBJECTIVE: to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools. METHODS: Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go - TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (T0) and after (T1) 14days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI. RESULTS: We found a significant difference between T0 and T1 for T25FW, TUG, MSWS-12 (p≤0.001) in the whole patients' sample (23 subjects, median EDSS 6.0) and decrease of Central Motor Conduction Time and increase of mean Amplitude (Amp) at T1 (p=0.008 and p=0.006). We also recorded a significant difference of T25FW, TUG, MSWS-12 and Amp in clinical responder (CR) patients (CR: amelioration >20% at T25FW). TBSS showed a significant Mean and Radial Diffusivity reduction in the corticospinal tracts (p<0.05) of the whole group of patients; this reduction was also found in the CR subgroup. CONCLUSION: Neurophysiological and neuroradiological parameters were modified in MS patients treated with 4-AP, and most of them reported a subjective improvement of their motor performances after treatment. The use of clinical, subjective, neurophysiological and neuroradiological tools could help to better explore MS patients responsiveness to 4-AP.

Individualized quality of life of severely affected multiple sclerosis patients: practicability and value in comparison with standard inventories.

PURPOSE: Individualized quality of life (QoL) measures differ from traditional inventories in that QoL domains/weights are not predetermined, but identified by the individual. We assessed practicability of the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW) interview in severely affected multiple sclerosis (MS) patients; the key QoL dimensions identified; and the correlation of the SEIQoL-DW index score with standard patient-reported outcome measures (PROMs). METHODS: Participants were people with severe MS who performed the baseline visit of the PeNSAMI trial (ISRCTN73082124). The SEIQoL-DW was administered at the patient's home by a trained examiner. Patients then received the following PROMs: the Core-Palliative care Outcome Scale (Core-POS), the Palliative care Outcome Scale-Symptoms-MS (POS-S-MS), the European Quality of Life Five Dimensions-3L (EQ-5D-3L), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Of 59 enrolled patients, 11 (19 %) did not receive the SEIQoL-DW (and the other PROMs) because of severe cognitive compromise or inability to communicate. SEIQoL-DW administration was completed and deemed valid in all 48 cases (mean age 60 years, 58 % women, median Expanded Disability Status Scale score 8.5). Mean SEIQoL-DW index score was 59.1 (SD 25.5). The most commonly nominated SEIQoL-DW areas were family (94 % of the patients), relationships, and leisure activities (both 65 %). Core-POS and POS-S-MS contained 70 % of the SEIQoL-DW-nominated areas. Nevertheless, correlations between SEIQoL-DW index, Core-POS, and POS-S-MS (and the other PROMs) were negligible. CONCLUSIONS: Individualized QoL can be assessed in severely affected MS patients, providing information that is not tracked by the standard inventories Core-POS, POS-S-MS, EQ-5D-3L, and HADS.

Caregiver's burden in disorders of consciousness: a longitudinal study.

OBJECTIVES: To study the changes in the burden of informal caregivers of patients with disorders of consciousness (DOC) over time. MATERIALS AND METHODS: Short Form-12, Family Strain Questionnaire, Beck Depression Inventory and Coping Orientations to Problem Experiences were administered. RESULTS: Data collected on 216 informal caregivers of patients with DOC (59.6% females, mean age 53.4 ± 12.7 years old) were analysed at two time-points (mean distance is 2.7 years). Results of the national study revealed that caregivers' mental health improved (T0: M = 41.1, SD = 11.8; T1: M = 45.8, SD = 11.7), whereas the emotional burden (T0: M = 7.4, SD = 3.6; T1: M = 6.6, SD = 3.9) and the presence of depressive symptoms (T0: M = 14.3, SD = 9.3; T1: M = 11.7, SD = 10.2) as well as the need for information about the disease (T0: M = 2.7, SD = 1.2; T1: M = 2.2, SD = 1.4), thoughts of death (T0: M = 3.6, SD = 1.5; T1: M = 3.1, SD = 1.6) and the use of avoiding coping strategy (T0: M = 7.8, SD = 1.0; T1: M = 6.0, SD = 1.3) decreased at T1. Furthermore, depressive symptoms positively correlated with the emotional burden (0.580) and negatively with the mental health component of caregivers' self-perceived health condition (-0.473). Physical (-0.308) and mental health (-0.444) negatively correlated with emotional burden. Finally, the acute event and patients' health condition still have a deep impact on the economic situation of the family. CONCLUSION: Although high level of burden was observed, it tends to decrease over time, except for financial burden. Hence, this study suggests the importance to plan strategies or targeted interventions in order to reduce the psychosocial and financial burden associated with caregiving.

Caregivers of patients with disorder of consciousness: burden, quality of life and social support.

OBJECTIVE: To evaluate quality of life (QoL) and its predictors, psychological burden and level of perceived social support in caregivers of patients with disorder of consciousness. MATERIALS & METHODS: World Health Organization Quality of Life-Bref (WHOQOL-BREF), State Trait Anxiety Inventory-Y (STAI-Y), Beck Depression Inventory (BDI-II), Prolonged Grief Disorder Questionnaire, Coping Orientations to Problem Experiences, State-Trait Anger Expression Inventory-2 (STAXI-2), and the Medical Outcome Study Social Support Survey (MOS-SSS) were administered. One-sample t-tests were performed to compare WHOQOL-BREF, STAI-Y and STAXI-2 mean scores to the respective normative sample (NS). Pearson correlation was calculated between time dedicated to patient's care, WHOQOL-BREF, BDI-II, STAI-Y and MOS-SSS scores. Hierarchical multiple regression analyses were performed to evaluate which variables have predictive power on QoL. RESULTS: A total of 129 caregivers, 68.2% female, mean age 52.8 years, were enrolled. Three WHOQOL-BREF domains were significantly lower. Anxiety and anger were in line with NS. 28.7% of the sample reported high level of depressive symptoms; 20.9% satisfied the prolonged grief disorder criteria. No differences emerged between caregivers and chronic ill patients' scores at MOS-SSS. STAI-Y, BDI-II and WHOQOL-BREF scores positively correlated. MOS-SSS domains inversely correlate with BDI-II scores. BDI-II results the most relevant predictor of QoL. CONCLUSIONS: Study results provided innovative information about caregivers' poor QoL, difficulties in social support and high levels of burden. Time dedicated to care is not strictly related to burden, while social support perceived is highly associated with caregivers' depressive symptoms that are strong predictor of poor QoL. Supportive intervention able to integrate psychological, social and environmental levels is needed.

Development and validation of the multiple sclerosis questionnaire for the evaluation of job difficulties (MSQ-Job).

OBJECTIVE: Multiple sclerosis (MS) affects young adults of working age. Difficulties in work-related activities are usually ascribed to MS symptoms, while the impact of workplace features is underestimated. This article presents the Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job), designed to assess working difficulties due to MS symptoms and workplace features. METHODS: A sample of employed MS patients completed the MSQ-Job, the WHO-Disability Assessment Schedule (WHODAS 2.0) and the 54-items MS Quality of Life Questionnaires (MSQOL-54); the expanded disability status scale (EDSS) was used to define MS severity. Factor structure was evaluated using principal component extraction and Oblimin rotation; internal consistency was assessed with Cronbach's alpha; construct and discriminant validity using t-test (EDSS 0-2 vs >2; patients self-reporting need for support vs patients reporting no needs; full-time vs part-time employees); and Pearson's correlation with WHODAS 2.0 and MSQOL-54. RESULTS: The MSQ-Job is a 42-item questionnaire with six scales and an overall factor. Scores range on a 0-100 scale (higher scores indicate more and more severe difficulties); patients with EDSS>2 and self-reporting support needs had worse scores than those with EDSS 0-2 and without needs. Correlations with WHODAS 2.0 and MSQOL-54 were generally significant (P < 0.0007) and below 0.70. CONCLUSIONS: The MSQ-Job jointly measures the impact of respondents' symptoms and workplace features on work activities and enables to assess the effects of clinical and occupational interventions and better describe the impact of MS indirect costs.

Informal caregivers of patients with disorders of consciousness: experience of ambiguous loss.

PRIMARY OBJECTIVE: This study aimed at better understanding of the complex psychological process underlying the demanding situation of taking care of a relative with disorder of consciousness (DOCs). RESEARCH DESIGN: This is a qualitative study based on the grounded theory constant comparative method. METHODS AND PROCEDURES: Narratives of informal caregivers were collected through in-depth interviews with a psychologist. A three-step coding scheme was applied: coding of narratives to label the specific contents; organization of codes into sub-categories and categories; and theoretical coding to describe the relation between categories. MAIN OUTCOMES AND RESULTS: Twenty informal caregivers participated in one in-depth interview between December 2011 and May 2012. Four major themes emerged: Another person with past in common; Losing and finding myself; Old and new ways of being in relationship; and Dealing with concerns. These themes represent caregivers' efforts to deal with the situation in which their relative is at the same time present and absent. The core salient feature emerging from all these themes is the experience of ambiguous loss. CONCLUSIONS: Features of ambiguous loss that emerged in this study could guide clinicians' interventions to support adjustment of caregivers of patients with DOCs.

Caregiving for patients in vegetative and minimally conscious states: perceived burden as a mediator in caregivers' expression of needs and symptoms of depression and anxiety.

Involvement of family members is crucial to provide daily informal caring to patients in vegetative state and minimally conscious state. Previous studies showed that perceived burden is a risk factor for informal caregivers as it increases psychophysical distress. This research further investigated the relationship between these factors and aimed at providing a model that thoroughly describes this mechanism of functioning. In the frame of a national survey on people with disorders of consciousness, 487 informal caregivers of children and adult patients in vegetative and minimally conscious state were administered measures of depression, anxiety, caregiver needs, and family strain. Regression models proposed by Baron and Kenny and the Sobel test were adopted to investigate the relationship between depressive and anxiety symptoms, perceived burden and needs expressed. Our study shows that the relation between those symptoms and needs is mediated by burden, where higher burden accentuates and lower burden mitigates the needs expressed by caregivers. Our findings demonstrate that psychosocial components of the burden perceived by caregivers of patients with disorders of consciousness play a key role in shaping those caregivers' needs, especially their needs for information and communication. We recommend implementation of comprehensive steps to meet the needs of these caregivers, steps that incorporate improved economic and public health programs, social support, and use of psychological interventions to ameliorate caregivers' psychological distress and decrease their burden.

Do diagnostic differences between vegetative state and minimally conscious state patients correspond to differences in functioning and disability profiles? Results from an observational multi-center study on patients with DOC.

BACKGROUND: Patients in vegetative (VS) and minimally conscious state (MCS) have different degrees of consciousness recovery but both display severe levels of disability. AIM: To describe and compare VS and MCS patients' functioning and disability according to ICF model (International Classification of Functioning, Disability and Health). DESIGN: Observational cross-sectional multi-center study involving sixty-nine Italian centers. SETTING: Patients recruited in post-acute, long-term care facilities and at home in Italy. POPULATION: Adult patients in VS and MCS. METHODS: ICF Functioning profiles were completed and, for each ICF chapter and domain, extension and severity indexes were developed. Indexes have been compared between VS and MCS patients with Mann Whitney U test. Descriptive statistics have been applied to describe the most relevant categories that had a percentage of missing below 25% and that were reported as a problem by at least 50% of patients. RESULTS: A total of 564 patients were enrolled: 396 in VS (mean age 56.8), 168 in MCS (mean age 54.2). Fifty-eight ICF categories were selected: of them, 24 were from Activity and Participation (A&P). Few differences between patients in VS and MCS were reported in Body Functions (BF), mostly referred to mental, sensory and digestive functions; among A&P, differences were found only in learning chapter. For VS patients less environmental barriers were reported than MCS patients. CONCLUSION: Patients in VS and MCS have similar functioning and disability profiles and similar needs thus levels of care and assistance should not be different across the two conditions. CLINICAL REHABILITATION IMPACT: An ICF-based methodology of data collection enables to describe VS and MCS patients' functioning and disability: this is helpful when rehabilitation programs based on the features of single patients with DOC need to be planned.

Physical and mental health, anxiety and depressive symptoms in caregivers of patients in vegetative state and minimally conscious state.

Caregivers of patients in vegetative state and minimally conscious state play a crucial role in the process of taking care and, as previous studies reported, they can suffer of high burden and negative health outcomes. The aim of this national cross-sectional study was to assess whether physical and mental health of caregivers, considering gender differences, is related to the presence of depressive symptoms, anxiety, age and patient's disease duration. Four-hundred and eighteen caregivers, 294 women and 124 men, completed the State Trait Anxiety Inventory-Y, Beck Depression Inventory, second version and Short Form-12. Hierarchical multiple regression analyses were performed to evaluate to which extent depressive and anxiety symptoms predict physical and mental health. Men reported higher levels of mental health state, whereas physical health was not different across gender. High levels of anxiety symptoms were associated to negative mental health outcomes in both genders, whereas depressive symptoms were found to impact on female's mental and physical health only. A comprehensive and cost-effective screening of anxiety and depressive symptoms may help to identify determinants of health worsening in order to plan, when necessary, caregivers' support. KEY PRACTITIONER MESSAGES: Female caregivers of patients in vegetative state and minimally conscious state have poorer levels of mental health, whereas physical health is similar to men's. Anxiety symptoms are related to negative mental health outcomes in both male and female caregivers, whereas depressive symptoms are found to impact on female mental and physical health only. It is essential to consider and assess depressive and anxiety symptoms as they may contribute to caregivers' health worsening. This knowledge can lead to plan more comprehensive and tailored caregivers' supports and a better care for patients.

Usefulness of ICF-CY to define functioning and disability in very low birth weight children: a retrospective study.

BACKGROUND: Preterm birth is associated with variable degrees of brain injury, adverse neurodevelopmental outcomes and continuing special health care needs. STUDY AND AIMS: This observational, retrospective and cross-sectional study aims to describe the functional features of VLBW infants using the ICF-CY classification and to identify the association between gender, twinship, birth weight, gestational age, adjusted age and functioning as defined by the ICF biopsychosocial model. SAMPLE: 56 VLBW infants (corrected age of 12-24 months) were consecutively enrolled. INSTRUMENTS: Three assessment tools were used: a neuro-functional assessment (NFA); the Griffiths Mental Development Scales-Revised: Birth to 2 years (Griffiths 0-2) to evaluate psychomotor development and the ICF-CY questionnaire for ages 0-3. RESULTS: A two-step cluster component analysis with the Bayesian information criterion was conducted based on NFA and Griffiths 0-2 scores and four groups of infant's functioning (very low, low, intermediate, high) emerged. Study findings demonstrate that the traditional assessment tools tend to poorly evaluate the interaction between the person's functioning and environment factors (EF), even thought EF results to be relevant for VLBW infants. The higher number of symptoms, more difficulties in activities and participations and the higher number of environmental facilitators maximize the difference between infants with very low and those with intermediate or higher functioning. The distribution of gender or the presence of siblings is not significantly associated to any group. CONCLUSION: This study shows that a more complete evaluation of functioning of VLBW children, based on the biopsychosocial approach, is needed and can be successfully implemented in the follow-up routine through ICF-CY questionnaire.

A 14-month study of change in disability and mood state in patients with chronic migraine associated to medication overuse.

This paper aims to evaluate changes in disease severity, disability and mood state in patients with chronic migraine associated to medication overuse (CM-MO). MIDAS was used for assessing disease activity, WHO-DAS-2 for disability, DBI-2 for mood state. ANOVA was used to test change over time; t-test to assess follow-up differences in WHO-DAS-2 and BDI-2 between patients with MIDAS ≤20 and ≥21. Change in MIDAS, WHO-DAS-2 and BDI-2 scores were computed: Pearson's index was used to assess correlation between them; linear regression to assess change in WHO-DAS-2, using MIDAS and BDI-2 change as predictors. Mean MIDAS decreased significantly (from 101.9 to 52.0). In 26.1 % of the sample, MIDAS fell below 21 at follow-up: these patients had lower WHO-DAS-2 score. WHO-DAS-2 change was little correlated to MIDAS change and strongly correlated to changes in BDI-2 scores. 57.1 % of WHO-DAS-2 change variance is explained by change in BDI-2 and MIDAS scores. There was a clear clinical improvement 14 months after detoxification, and a modest reduction in disability which is explained by reduced disease activity and improved mood state. An appropriate treatment of CM-MO, based on detoxification and prophylaxis, is likely to reduce disease burden: recognition and treatment of mood problems may be a key factor to reduce disability.

Burden of caregivers of patients in Vegetative state and minimally conscious state.

OBJECTIVES: To assess differences in the burden of caregivers of patients in Vegetative state (VS) and minimally conscious state (MCS). MATERIALS AND METHODS: The Family Strain Questionnaire, Coping Orientations to Problem Experiences, Caregiver Needs Assessment, Short Form-12, Beck Depression Inventory and State-Trait Anxiety Inventory were used. Differences in psychological condition between caregivers of VS and MCS patients, with different disease duration and hosting facility were assessed with Kruskall-Wallis test and factors associated with the overall levels of burden with UNIANOVA. RESULTS: In total, 487 participants were enrolled. Daily hours of care-giving is significantly associated with the overall level of burden perceived by caregivers (F = 4.099; P = 0.018). Strain, needs and frequency of use of coping strategies are substantially similar regardless of the patient's condition and distance from the acute event. Caregivers of post-acute patients reported low scores in mental health (median = 33.8; IQR = 23.1-47.6) and higher state of anxiety (median = 54; IQR = 45-62), whereas caregivers of long-term patients expressed more needs in social involvement (median = 19; IQR = 15-22). CONCLUSIONS: Burden and distress were high for all caregivers of VS and MCS patients. As care-giving is a long-term commitment process, support to the caregiver should be guaranteed throughout the duration of the relative's disease despite the patient's diagnosis or place where the patient is hosted.

Disability and mood state in patients with episodic and chronic migraine associated to medication overuse.

This study aims to compare disability and mood state in patients with episodic (EM) and chronic migraine associated to medication overuse (CM-MO), and to assess the relationships between the two outcomes. Patients, matched for age and gender, were administered the MIDAS, the WHO-DAS-2 and BDI-2. Difference between EM and CM-MO was assessed with the Kolmogorov-Smirnov Test; difference in distribution of patients with severe disability and low mood was tested with contingency coefficient; the correlation between MIDAS, WHO-DAS-2 and BDI-2 was tested with Spearman's index. Seventy patients were enrolled: CM-MO patients reported higher BDI-2 scores and higher MIDAS and WHO-DAS-2 scores, and were more likely to have severe disability and low mood state than those with EM; BDI-2 scores were correlated with disability scores, particularly with WHO-DAS-2. The study shows that disability and mood state are negatively impacted by the presence of more frequent headaches and by the overuse of acute medications.

Burden and needs of 487 caregivers of patients in vegetative state and in minimally conscious state: results from a national study.

OBJECTIVE: The aim of this study is to evaluate the burden of caregivers of patients with disorders of consciousness (DOCs), considering psychosocial difficulties, health condition and financial aspects. DESIGN: This is an observational multi-centre study. Four hundred and eighty-seven participants were assessed using the Caregiver Needs Assessment, Family Strain Questionnaire, Short Form 12, Spielberger State Trait Anxiety Inventory-Y, Beck Depression Inventory, Prolonged Grief Disorder Questionnaire and Coping Orientations to Problem Experiences. OUTCOMES AND RESULTS: The sample had lower scores both in Physical (M = 49.85, SD = 7.66) and Mental (M = 39.37, SD = 12.90) health and a higher level of anxiety (p < 0.001) in comparison to the Italian normative sample. More than half of the sample manifested a high level of depressive symptoms (59.5%) and 27.6% satisfied criteria for Prolonged Grief Disorder. This sample reported needs to know the disease of their beloved, high needs for information and communication, several problems in social involvement and in emotional burden. The most frequently adopted coping strategies are acceptance, turning to religion, positive reinterpretation and planning. Finally, 40.2% of caregivers report to earn a net income of less than 17 000 euros per year. CONCLUSIONS: These results showed a high burden related to providing care to patients with DOCs. This study sets the scene to plan comprehensive support strategies for caregivers in order to diminish level of burden.

Children in vegetative state and minimally conscious state: patients' condition and caregivers' burden.

Caring for children in vegetative state (VS) or minimally conscious state (MCS) challenges parents and impacts on their well-being. This study aims to evaluate caregivers' health condition, coping, anxiety and depression levels, and how these issues relate to children's disability. 35 children with VS and MCS were administered the disability rating scale (DRS) and 35 caregivers completed the Coping Orientations to Problem Experiences, Short Form-12, Beck Depression Inventory, and the Spielberger State-Trait Anxiety Inventory-Y. Children were mainly males (68.6%), hosted at domicile (77.1%), and diagnosed with VS (60%), with anoxic aetiology (45.7%). Caregivers were mainly mothers (85.7%), married (82.9%), and housewives (51.4%); 60% declared financial difficulties, and 82.9% provided full-time assistance. 57.2% reported depressive symptoms, poor mental health, and high level of state and trait anxiety. "Problem-oriented" (P < 0.001) and "emotional-oriented" (P < 0.001), were more adopted than "potentially dysfunctional" ones. DRS scores (mean = 22.0; SD = 1.9) did not significantly correlate to any psychological measure. Rehabilitative programs for children with SV and SMC should also provide interventions on surrounding systems: improving the network of psychological support and social assistance may decrease the burden of caregivers and, in turn, improve caring abilities and children quality of life.

Multidisciplinary approach to extracorporeal respiratory assist for acute pulmonary failure.

A case of acute post-traumatic pulmonary failure was treated by extracorporeal respiratory assist, after conventional therapy had failed. Veno-venous bypass was established, with low extracorporeal blood flow (1.6-2 l min-1), and high exchange surface area membrane lungs (7 m2), according to the technique of low-frequency positive-pressure ventilation with extracorporeal carbon-dioxide removal. After a first disconnection, the evolution of the lung disease necessitated a second surgical procedure, during which a chest tube perforated the patient's right lower, pulmonary lobe. A two-stage right thoracotomy was performed, with the patient connected to the extracorporeal system, and receiving full heparinization. Massive bleeding and severe hypoxia were encountered, but successfully overcome. The patient is now a long-term survivor.

Changes in renin, water balance, and sodium balance during development of high blood pressure in genetically hypertensive rats.

In genetically hypertensive rats of the Milan hypertensive strain (MHS) and normotensive rats (NR) developed from the same Wistar stock colony, blood pressure (BP), plasma renin activity (PRA), sodium balance, and water balance were measured from the time of weaning to the seventh week postweaning in three separate but essentially identical experiments. In a fourth experiment, total and extracellular water, total sodium, and exchangeable sodium were measured in MHS and NR at 24 and 130 days of age. Although the time course of changes varied slightly between experiments, BP of both NR and MHS rose until the second and third weeks postweaning, at which time BP in MHS was 40 to 50 mm Hg higher than in NR. PRA in MHS was one-half that of NR at weaning. Increasing BP was accompanied by falling PRA in both, and PRA was not significantly different when stable, adult blood pressure was reached. Urinary volume in MHS was 50% to 100% greater (P less than 0.001) than in NR at weaning and for a few days after. Sodium was retained to a greater extent by MHS during the period when the blood pressure difference develops, from weaning to the fourth week postweaning. This sodium retention (MHS = 97.0 plus or minus 10.3, NR = 65.2 plus or minus 6.8 SE mu-Eq Na retained/g body weight gain; P less than 0.005) is the result of significantly lower urinary excretion of dietary sodium by MHS. A causative role for the kidney is suggested in the established of high blood pressure in MHS.