The effectiveness of a family-centred intervention after traumatic brain injury: A pragmatic randomised controlled trial.

OBJECTIVES: To determine the effectiveness of a family-centred intervention for patients with traumatic brain injury and family members. DESIGN: Open-labelled, two-armed randomised controlled trial. SETTINGS: Outpatient clinic and family residences. PARTICIPANTS: Sixty-one patients (33 women) with traumatic brain injury, with mean (SD) age 43.8 (12.2), and 63 family members (33 women), with mean (SD) age 42.6 (11.3), were assign to intervention (n = 30 families) and control group (n = 31 families). INTERVENTION: An eight-session single-family intervention to improve individual and family functioning. OUTCOME MEASURES: Self-reported questionnaires at start-of-treatment, median (IQR) 11.4 (8.4, 15.9) months post-injury, and at two follow-ups, 2.7 (2.3, 3.8) and 9.2 (8.2, 9.9) months after start-of-treatment. Primary outcome measures were the SF-36 Mental Component Summary (MCS) and Caregiver Burden Scale (CGB). Secondary outcome measures were the Family Adaptability and Cohesion Evaluation Scale (FACES) and Quality of Life after Brain Injury Questionnaire (QOLIBRI). Group differences were analysed with linear mixed-model analysis for repeated measurements. RESULTS: No significant between-group differences were found. The intervention group significantly improved on the MCS, the CGB and FACES in the treatment period, whereas the controls did not. The mean (SD) MCS change in the treatment period was 2.4 (1.1) points P = 0.028 in the intervention group. Mean (SE) MCS scores were 47.9 (1.26) and 47.3 (1.27) in the intervention and control group at last follow-up. CONCLUSIONS: Receiving an eight-session family intervention, in addition to specialised rehabilitation for the patients, was not superior to rehabilitation at a specialised traumatic brain injury outpatient clinic.

Mental Health and Family Functioning in Patients and Their Family Members after Traumatic Brain Injury: A Cross-Sectional Study.

Traumatic brain injury (TBI) affects the family as a whole. This study aimed to describe and compare mental health and family functioning in TBI patients and their family members, and to identify individual and family-related factors that were associated with mental health. It was conducted at an urban, specialized, TBI outpatient clinic and included 61 patients with mild to severe TBI and 63 family members. Baseline demographics and injury-related data were collected, and the participants answered standardized, self-reported questionnaires 6-18 months post-injury that assessed mental health; general health; family functioning, communication, and satisfaction; depression and anxiety; self-efficacy; resilience; and condition-specific quality of life. The patients reported significantly worse mental health, depression, resilience, self-efficacy, and general health compared with the family members. Patients and family members had similar perceptions, showing balanced family functioning, high family communication levels, and moderate family satisfaction. Factors significantly associated with mental health in patients and family members were depression, anxiety, and resilience, explaining 56% of the variance (p < 0.001). Family-related factors were not associated with mental health. The disease burden was mainly on the patients; however, the family members also reported emotional distress. Family-targeted interventions across the TBI continuum should be considered.

Encephalitis and aseptic meningitis: short-term and long-term outcome, quality of life and neuropsychological functioning.

For those surviving encephalitis, the influence on daily life of patients and their relatives may be substantial. In contrast, the prognosis after aseptic meningitis (ASM) is considered good. In this prospective study in patients with encephalitis (n = 20) and ASM (n = 46), we show that both groups experienced reduced Health Related Quality of Life (HRQoL) at two months after discharge, and that workability was reduced in 37% of the patients with ASM. However, 12 months after discharge no neuropsychological deficits were detected in the ASM group, whereas patients with encephalitis had lower scores on tests of fine motor and psychomotor skills as well as on learning and memory. We also found that for patients with encephalitis, neopterin, as a marker of Th1 cell induced macrophage activation, and a putatively neurotoxic ratio of the kynurenine pathway (KP) measured during the acute phase was associated with lower HRQoL. Our data show that not only encephalitis, but also ASM has substantial short-term influence on HRQoL and workability. For patients with encephalitis we suggest a link between immune activation and activation of the KP during the acute phase with impaired HRQoL.

Novel UCHL1 mutations reveal new insights into ubiquitin processing.

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 has been implicated in early-onset progressive neurodegeneration (MIM no. 615491), so far only in one family. In this study a second family is characterized, and the functional consequences of the identified mutations in UCHL1 are explored. Three siblings developed childhood-onset optic atrophy, followed by spasticity and ataxia. Whole exome sequencing identified compound heterozygous variants in UCHL1, c.533G > A (p.Arg178Gln) and c.647C > A (p.Ala216Asp), cosegregating with the phenotype. Enzymatic activity of purified recombinant proteins analysed by ubiquitin hydrolase assays showed a 4-fold increased hydrolytic activity of the recombinant UCHL1 mutant Arg178Gln compared to wild type, whereas the Ala216Asp protein was insoluble. Structural 3D analysis of UCHL1 by computer modelling suggests that Arg178 is a rate-controlling residue in catalysis which is partly abolished in the Arg178Gln mutant and, consequently, the Arg178Gln mutant increases the enzymatic turnover. UCHL1 protein levels in fibroblasts measured by targeted mass spectrometry showed a total amount of UCHL1 in control fibroblasts about 4-fold higher than in the patients. Hence, studies of the identified missense variants reveal surprisingly different functional consequences as the insoluble Ala216Asp variant leads to loss of function, whereas the Arg178Gln leads to increased enzyme activity. The reported patients have remarkably preserved cognition, and we propose that the increased enzyme activity of the Arg178Gln variant offers a protective effect on cognitive function. This study establishes the importance of UCHL1 in neurodegeneration, provides new mechanistic insight about ubiquitin processing, and underlines the complexity of the different roles of UCHL1.