Causative gene mutations have been identified in about 2% of those with amyotrophic lateral sclerosis (ALS), often, but not always, when there is a strong family history. There is an assumption that ...there is a genetic component to all ALS, but genome-wide association studies have yet to produce a robustly replicated result. A definitive estimate of ALS heritability is therefore required to determine whether ongoing efforts to find susceptibility genes are worth while.
The authors performed two twin studies, one population- and one clinic-based. The authors used structural equation modelling to perform a meta-analysis of data from these studies and an existing twin study to estimate ALS heritability, and identified 171 twin pairs in which at least one twin had ALS.
Five monozygotic twin pairs were concordant-affected, and 44 discordant-affected. No dizygotic twin pairs were concordant-affected, and 122 discordant-affected. The heritability of sporadic ALS was estimated as 0.61 (0.38 to 0.78) with the unshared environmental component 0.39 (0.22 to 0.62). ALS has a high heritability, and efforts to find causative genes should continue.
We sought to define the significance of brachial amyotrophic diplegia (flail arm syndrome FA) and the pseudopolyneuritic variant (flail leg syndrome FL) of amyotrophic lateral sclerosis (ALS; motor ...neuron disease).
We analyzed survival in clinic cohorts in London, UK (1,188 cases), and Melbourne, Australia (432 cases). Survival from disease onset was analyzed using the Kaplan- Meier method and Cox proportional hazards model.
In the London cohort, the FA syndrome represented 11% and the FL syndrome 6% of the sample. Median survival was 35 months for limb onset and 27 months for bulbar onset ALS, whereas this was 61 months for FA syndrome (p < 0.001) and 69 months for FL syndrome (p < 0.001). Five-year survival in this cohort was 8.8% for bulbar onset, 20% for limb onset, 52% for FA syndrome, and 64% for FL syndrome. The ratio of men to women was 4:1 in the FA group compared to 2:1 in other limb onset cases. Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. In the Melbourne cohort, median survival for limb onset ALS was 31 months, bulbar onset 27 months, FA syndrome 66 months (p < 0.001), and FL syndrome 71 months (p = 0.001).
The flail arm (FA) and flail leg (FL) syndromes had significantly better survival than typical amyotrophic lateral sclerosis (ALS) or progressive muscular atrophy cases that were not classified as FA or FL. Our findings underline the clinical and prognostic importance of the FA and FL variants of ALS.
The cognitive impairment revealed in some non‐ demented amyotrophic lateral sclerosis (ALS) patients is characterized by executive dysfunction with widely repeated deficits on tests of verbal ...(letter) fluency. However, conflicting evidence exists of an impairment on other word retrieval tasks, such as confrontation naming, which do not place heavy demands on executive processes. Previous research has demonstrated intact confrontation naming in the presence of verbal fluency deficits, although naming deficits have been described in other studies. In this investigation, functional MRI (fMRI) techniques were employed to explore whether word retrieval deficits and underlying cerebral abnormalities were specific to letter fluency, which are more likely to indicate executive dysfunction, or were also present in confrontation naming, indicating language dysfunction. Twenty‐eight non‐demented ALS patients were compared with 18 healthy controls. The two groups were matched for age, intelligence quotient, years of education, and anxiety and depression scores. Two compressed‐sequence overt fMRI activation paradigms were employed, letter fluency and confrontation naming, which were developed for use with an older and potentially impaired population. In ALS patients relative to controls, the letter fluency fMRI task revealed significantly impaired activation in the middle and inferior frontal gyri and anterior cingulate gyrus, in addition to regions of the parietal and temporal lobes. The confrontation naming fMRI task also revealed impaired activation in less extensive prefrontal regions, including the inferior frontal gyrus and regions of the temporal, parietal and occipital lobes. These changes were present despite matched performance between patients and controls during each activation paradigm. The pattern of dysfunction corresponded to the presence of cognitive deficits on both letter fluency and confrontation naming in the ALS group. This study provides evidence of cerebral abnormalities in ALS in the network of regions involved in language and executive functions. Moreover, the findings further illustrate the heterogeneity of cognitive and cerebral change in ALS.
The objective was to identify factors associated with decisions made by patients with amyotrophic lateral sclerosis (ALS) to accept or decline non-invasive ventilation (NIV) and/or gastrostomy in a ...prospective population-based study. Twenty-one people with ALS, recruited from the South-East ALS Register who made an intervention decision during the study timeframe underwent a face-to-face in-depth interview, with or without their informal caregiver present. Sixteen had accepted an intervention (11 accepted gastrostomy, four accepted NIV and one accepted both interventions). Five patients had declined gastrostomy. Thematic analysis revealed three main themes: (1) patient-centric factors (including perceptions of control, acceptance and need, and aspects of fear); (2) external factors (including roles played by healthcare professionals, family, and information provision); and (3) the concept of time (including living in the moment and the notion of ‘right thing, right time’). Many aspects of these factors were inter-related. Decision-making processes for the patients were found to be complex and multifaceted and reinforce arguments for individualised (rather than ‘algorithm-based’) approaches to facilitating decision-making by people with ALS who require palliative interventions.
Systematic explorations of language abilities in patients with amyotrophic lateral sclerosis (ALS) are lacking in the context of wider cognitive change.
Neuropsychological assessment data were ...obtained from 51 patients with ALS and 35 healthy controls matched for age, gender and IQ. Composite scores were derived for the domains of language and executive functioning. Domain impairment was defined as a composite score ≤5th centile relative to the control mean. Cognitive impairment was also classified using recently published consensus criteria.
The patients with ALS were impaired on language and executive composite scores. Language domain impairment was found in 43% of patients with ALS, and executive domain impairment in 31%. Standardised language and executive composite scores correlated in the ALS group (r=0.68, p<0.001). Multiple regression analyses indicated that scores on the executive composite accounted for 44% of the variance in language composite scores.
Language impairments are at least as prevalent as executive dysfunction in ALS. While the two domains are strongly associated, executive dysfunction does not fully account for the profile of language impairments observed, further highlighting the heterogeneity of cognitive impairment in non-demented patients with ALS.
To investigate longitudinally the profile of cognitive impairment in nondemented patients with ALS.
Twenty nondemented patients with ALS and 18 controls were interviewed at two time points separated ...by a 6-month interval. The extensive battery was designed to accommodate the range of physical disability present in ALS, and included measures of executive, memory, language, and visuospatial functions, everyday behavior, and emotion.
On a test of simple word retrieval (Computerised Sentence Completion Test) patients with ALS became slower over time, while controls became faster at completing sentences with appropriate words. This effect remained when the analysis accommodated for progressive speech disability. Patients with ALS also displayed an impairment in both written and spoken verbal fluency indices (time to think of each word) at both time points, but there was no evidence of deterioration over time. On the Short Inventory of Minor Lapses, carers of patients with ALS displayed increased awareness of cognitive dysfunction in everyday behavior while controls' ratings of their partners decreased. In addition, patients displayed more depressive symptomology (although well below clinical levels) on the second interview vs controls. Patients with ALS also displayed emotional lability at both time points, although this did not increase over time.
Cognitive deterioration in nondemented patients with ALS is a relatively slow process. Selective cognitive impairment in the form of verbal fluency deficits, most likely indicating executive dysfunction, appears relatively early on in the course of the disease, although language functions may become vulnerable as the disease progresses.
Aim
Large marine predators, such as cetaceans and sharks, play a crucial role in maintaining biodiversity patterns and ecosystem function, yet few estimates of their spatial distribution exist. We ...aimed to determine the species richness of large marine predators and investigate their fine‐scale spatiotemporal distribution patterns to inform conservation management.
Location
The Hauraki Gulf/Tīkapa Moana/Te Moananui‐ā‐Toi, Aotearoa/New Zealand.
Methods
We conducted a replicate systematic aerial survey over 12 months. Flexible machine learning models were used to explore relationships between large marine predator occurrence (Bryde's whales, common and bottlenose dolphins, bronze whaler, pelagic and immature hammerhead sharks) and environmental and biotic variables, and predict their monthly distribution and associated spatially explicit uncertainty.
Results
We revealed that temporally dynamic variables, such as prey distribution and sea surface temperature, were important for predicting the occurrence of the study species and species groups. While there was variation in temporal and spatial distribution, predicted richness peaked in summer and was the highest in coastal habitats during that time, providing insight into changes in distributions over time and between species.
Main Conclusions
Temporal changes in distribution are not routinely accounted for in species distribution studies. Our approach highlights the value of multispecies surveys and the importance of considering temporally variable abiotic and biotic drivers for understanding biodiversity patterns when informing ecosystem‐scale conservation planning and dynamic ocean management.
Neuroimaging and neuropsychological studies have revealed that the primary motor cortex (PMC) and the extramotor cortical areas are functionally abnormal in motor neuron disease (MND, amyotrophic ...lateral sclerosis), but the nature of the cortical lesions that underlie these changes is poorly understood. In particular, there have been few attempts to quantify neuronal loss in the PMC and in other cortical areas in MND. We used SMI‐32, an antibody against an epitope on non‐phosphorylated neurofilament heavy chain, to analyse the size and density of SMI‐32‐positive cortical pyramidal neurons in layer V of the PMC, the dorsolateral prefrontal cortex (DLPFC) and the supragenual anterior cingulate cortex (ACC) in 13 MND and eight control subjects. There was a statistically significant reduction in the density of SMI‐32‐immunoreactive (IR) pyramidal neurons within cortical layer V in the PMC, the DLPFC and the ACC in MND subjects compared with controls t (19) = 2.91, P = 0.009; estimated reduction 25%; 95% CI = 8%, 40%. In addition, we studied the density and size of interneurons immunoreactive for the calcium‐binding proteins calbindin‐D28K (CB), parvalbumin (PV) and calretinin (CR) in the same areas (PMC, DLPFC and ACC). Statistically significant differences in the densities of CB‐IR neurons were observed within cortical layers V (P = 0.003) and VI (P = 0.001) in MND cases compared with controls. The densities of CR‐ and PV‐IR neurons were not significantly different between MND and control cases, although there were trends towards reductions of CR‐IR neuronal density within the same layers and of PV‐IR neuronal density within cortical layer VI. Loss of pyramidal neurons and of GABAergic interneurons is more widespread than has been appreciated and is present in areas associated with neuroimaging and cognitive abnormalities in MND. These findings support the notion that MND should be considered a multisystem disorder.
Accessible summary
Current UK mental health nursing policy is critiqued for neglecting the storied complexities of recovery‐survival.
Within a critical framework, creative non‐fiction is used in a ...relational auto‐ethnographic design to produce two short stories that demonstrate the utility of narrative re‐storying in recovery‐survival.
New insights emerge for mental health nurse practice and research. These are: that narrative re‐storying may help the recovery process for individuals and communities; that hybrid transcultural writing positively undermines barriers between professionals and consumers of mental health; and that all of this constitutes contemporary methodological innovation in narrative inquiry and related practice.
Some of the complexities of recovery and survival are arguably relatively neglected in current UK mental health nursing policy and, by association, clinical and research practice. In order to redress this, this paper, part of larger research project, will present two short stories, contextualized in a critical theoretical and methodological position. The overall significance of the argument in the paper is in its emerging benefits and implications for users of mental health services, practitioners and researchers. The central, orienting principle in the paper, cohering with all of its strands, is ‘narrative re‐storying’. Organized in three parts, the first reviews selected relevant background policy and related literature, the contextual and theoretical bases of the paper, and related methodological and ethical issues. The second presents the two stories, and the third brings the paper to a close. It does so in discussing specific and global emerging implications for mental health nursing practice and research, around narrative re‐storying as a recovery tool and methodological innovations that include ‘hybrid’ writing.
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