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Objective: This study uses three linked datasets to provide an estimate of incidence of motor neuron disease (MND) in England from 1998 to 2019. Comparison is made to previous British studies. It examines age at diagnosis and ethnicity of those affected. Methods: The literature was searched for studies of MND incidence in Great Britain from 1995 to date. The QResearch and linked Hospital Episode Statistics and Death register databases were searched from 1998 to 2019 for cases of MND, and incidence calculated from 16.8 million adults and 112 million adult years of data. Results: We found 6437 adults with a diagnosis of MND giving an incidence of MND of 5.69/100,000 person years (95% CI 5.51–5.88); 6.57 (6.41–6.99) in men and 4.72 (4.49–4.97) in women when age-standardized to the 2011 UK population. The median age of diagnosis was 72 years. Peak incidence occurred in the 80–84 year age group in men and 75–79 in women. Age-standardized incidence was as high in Bangladeshi, Black Caribbean, Indian, other Asian and Pakistani people as in White people. Black African and Chinese people had a lower incidence. Conclusion: The use of three linked national datasets captured 33% more people than a primary care dataset alone. Patients were older than in previous studies and rates were high in all ethnic groups studied except Black African and Chinese people. We present the highest incidence of MND reported globally in the past 50 years. Methodological differences may in part explain differences with previous reports. The use of national datasets may have captured additional MND patients with serious comorbidities who have not seen a neurologist before death. A limitation of this approach is that unlike population registers, which minimize false positive diagnosis by neurologist review of each patient, we cannot review diagnosis for individuals as data are anonymized. [ABSTRACT FROM AUTHOR]

Background Crossover in the pathogenic mechanisms of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) has been described but is poorly understood. A GGGGCC hexanucleotide repeat expansion of C9ORF72 has recently been identified in a significant proportion of patients with ALS. Methods In approximately 650 patients diagnosed with ALS from the North of England we identified seven patients who initially presented with MS. DNA obtained from five patients with MS-ALS and 215 patients with MS alone was screened for the C9ORF72 expansion. Post-mortem material was examined from two patients with MS-ALS. Gene expression profiling was performed on lymphoblastoid cells and levels of CXCL10 were measured in cerebrospinal fluid (CSF) from patients with ALS with and without the C9ORF72 expansion and controls. Results Concurrence of MS and ALS is higher than expected in our population. The C9ORF72 expansion was identified in 80% of patients with MS-ALS but not in those with MS alone. In the presence of preceding MS, C9ORF72-ALS was more rapidly progressive. MetaCore analysis identified alteration of the NF-kB pathway in C9ORF72-ALS and non-C9ORF72-ALS. NF-kB activation is associated with increased expression of the neuroprotective cytokine CXCL10 but, in C9ORF72-ALS, CXCL10 is downregulated and CSF levels are reduced. Conclusions We propose that MS-associated neuroinflammation may affect penetrance and progression of the C9ORF72 expansion. In particular, the NF-kB pathway is activated in MS and appears to be dysfunctional in C9ORF72-ALS. Aberrant downregulation of CXCL10 may explain the predisposition of C9ORF72 expansion carriers to develop ALS in the context of MS and NF-kB activation, and offers a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) is a systemic and fatal neurodegenerative condition for which there is currently no cure. Informal caregivers play a vital role in supporting the person with ALS, and it is essential to support their wellbeing. This multi-centre, mixed methods descriptive exploratory study describes the complexity of burden and self-defined difficulties as described by the caregivers themselves. Quantitative and qualitative data were collected during face-to-face interviews with informal caregivers from centres in the Netherlands, England, and Ireland. Standardised measures assessed burden, quality of life, and psychological distress; furthermore, an open-ended question was asked about difficult aspects of caregiving. Most caregivers were female, spouse/partners, and lived with the person with ALS for whom they provided care. Significant differences between national cohorts were identified for burden, quality of life, and anxiety. Among the difficulties described were the practical issues associated with the caregiver role and emotional factors such as witnessing a patient's health decline, relationship change, and their own distress. The mixed-methods approach allows for a more nuanced understanding of the burden and difficulties experienced. It is important to generate an evidence base to support the psychosocial wellbeing and brain health of informal caregivers. [ABSTRACT FROM AUTHOR]