Delivering cognitive analytic consultancy to community mental health teams: Initial practice-based evidence from a multi-site evaluation.

Objectives: This study sought to employ the hourglass model to frame the methodological evolution of outcome studies concerning 5-session cognitive analytic consultancy (CAC).

Design: Pre-post mixed methods evaluation (study one) and mixed methods case series (study two).

Methods: In study one, three sites generated acceptability and pre-post effectiveness outcomes from N = 58 care dyads, supplemented with qualitative interviewing.

C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study.

Objective: To determine the histopathologic bases for the observed incidence of parkinsonism in families with C9ORF72 expansions, which typically cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia.

Methods: DNA was extracted from 377 brains with the histopathologic diagnosis of idiopathic Parkinson disease or related disorders and analyzed for C9ORF72 expansions. α-Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was undertaken in brains of 17 ALS cases with (C9ORF72+) and 51 without (C9ORF72-) the C9ORF72 expansion.

Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72.

Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron disease in both familial and sporadic cases. Initial reports indicate that this variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum is associated with transactive response DNA binding protein (TDP-43) proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype is not yet well characterized.

Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis.

Objective: To determine the frequency of and clinicopathologic phenotypes associated with FUS/TLS mutations in a large cohort of amyotrophic lateral sclerosis (ALS) cases from the north of England.

Design: Genetic screening project with neuropathologic examination of postmortem tissue in selected cases. The clinical details of selected cases are also presented.

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B.

Living with cancer-related fatigue: developing an effective management programme.

A fatigue management programme was developed for hospice day care patients. Following feedback, and using the survivorship agenda, the authors found that cancer-related fatigue was a major difficulty for many patients. Fatigue, which affects 'normal' functioning and quality of life, is often related to cancer treatments which continue even after the patient has completed active treatment.

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis.

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases).

Screening of the transcriptional regulatory regions of vascular endothelial growth factor receptor 2 (VEGFR2) in amyotrophic lateral sclerosis.

Background: Vascular endothelial growth factor (VEGF) has neurotrophic activity which is mediated by its main agonist receptor, VEGFR2. Dysregulation of VEGF causes motor neurone degeneration in a mouse model of amyotrophic lateral sclerosis (ALS), and expression of VEGFR2 is reduced in motor neurones and spinal cord of patients with ALS.

Methods: We have screened the promoter region and 4 exonic regions of functional significance of the VEGFR2 gene in a UK population of patients with ALS, for mutations and polymorphisms that may affect expression or function of this VEGF receptor.

Large-scale pathways-based association study in amyotrophic lateral sclerosis.

Sporadic amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, most likely results from complex genetic and environmental interactions. Although a number of association studies have been performed in an effort to find genetic components of sporadic ALS, most of them resulted in inconsistent findings due to a small number of genes investigated in relatively small sample sizes, while the replication of results was rarely attempted. Defects in retrograde axonal transport, vesicle trafficking and xenobiotic metabolism have been implicated in neurodegeneration and motor neuron death both in human disease and animal models.

Investigation of the mitochondrial genome in patients with atypical motor neuron disease.

The molecular aetiology of many patients with motor neuron disease (MND) remains unknown. Recent evidence of mitochondrial dysfunction, in particular the finding of histochemical abnormalities and pathogenic mitochondrial DNA (mtDNA) mutations, has prompted us to investigate further the role of mtDNA abnormalities in a cohort of thirteen patients with atypical MND presentations by whole mitochondrial genome sequencing. No pathogenic mutations were detected suggesting that inherited mtDNA mutations are not a common cause of atypical MND presentations.