John McConville

Background Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder caused by expansion of a CTG trinucleotide repeat in the 3′ untranslated region of the DMPK gene. Several studies have reported increased cancer incidence in individuals with DM1, but estimates have varied and a previous meta-analysis was limited by studies with small sample sizes. We performed an updated systematic review and meta-analysis to quantify overall and site-specific cancer risk in DM1. Methods MEDLINE, Embase and Web of Science were searched from database inception to 6 January 2026. Studies reporting cancer incidence in individuals with DM1 were included. Standardised incidence ratios (SIRs) were pooled using random-effects meta-analysis. Hazard ratios and relative risks reported by studies using alternative comparator populations were summarised descriptively. Heterogeneity was assessed using I², Cochran's Q, tau-squared and 95% prediction intervals. Results Eleven studies met inclusion criteria. Five studies comprising 7,443 individuals with DM1 contributed data to the primary meta-analysis. The pooled Standardised Incidence Ratio (SIR) for all cancers was 1.74 (95% CI 1.51-2.00; I²=40.6%). Site-specific analyses demonstrated significant increases in risk for ovarian cancer (SIR 8.08, 95% CI 3.92–16.67), uterine cancer (SIR 7.15, 95% CI 4.72–10.83), brain cancer (SIR 6.68, 95% CI 4.06–11.01), thyroid cancer (SIR 5.45, 95% CI 2.14–13.91), pancreatic cancer (SIR 3.69, 95% CI 2.02–6.75), liver cancer (SIR 2.97, 95% CI 1.89–4.68), lymphoma (SIR 2.20, 95% CI 1.17–4.15), melanoma (SIR 1.92, 95% CI 1.10–3.36) and colorectal cancer (SIR 1.92, 95% CI 1.41–2.60). Breast and lung cancer were not significantly elevated. Heterogeneity was low for most site-specific analyses. Conclusions Individuals with DM1 experience a significantly increased incidence of cancer. Cancer risk is not uniformly elevated across tissues, with marked increases observed for selected malignancies and little evidence of excess risk for others. These findings support enhanced awareness of cancer susceptibility in DM1 and suggest that DM1 may provide a useful model for investigating relationships between somatic repeat instability and carcinogenesis.

Neurofilament levels are elevated in many neurodegenerative diseases and have shown promise as diagnostic and prognostic biomarkers in Amyotrophic Lateral Sclerosis (ALS), the most common form of Motor Neuron Disease (MND). This study assesses serum neurofilament light (NFL) and neurofilament heavy (NFH) chain concentrations in patients with ALS, other variants of motor neuron disease such as Progressive Muscular Atrophy (PMA) and Primary Lateral Sclerosis (PLS), and a range of other neurological diseases. It aims to evaluate the use of NFL and NFH to differentiate these conditions and for the prognosis of MND disease progression. NFL and NFH levels were quantified using electrochemiluminescence immunoassays (ECLIA). Both were elevated in 47 patients with MND compared to 34 patients with other neurological diseases and 33 healthy controls. NFL was able to differentiate patients with MND from the other groups with a Receiver Operating Characteristic (ROC) curve area under the curve (AUC) of 0.90 (p < 0.001). NFL correlated with the rate of disease progression in MND (rho 0.758, p < 0.001) and with the ALS Functional Rating Scale (rho −0.335, p = 0.021). NFL levels were higher in patients with ALS compared to both PMA (p = 0.032) and PLS (p = 0.012) and were able to distinguish ALS from both PMA and PLS with a ROC curve AUC of 0.767 (p = 0.005). These findings support the use of serum NFL to help diagnose and differentiate types of MND, in addition to providing prognostic information to patients and their families.

Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), and Spinal Muscular Atrophy (SMA) are motor neuron diseases (MNDs) characterised by progressive motor neuron degeneration, weakness and muscular atrophy. Lipid dysregulation is well recognised in each of these conditions and occurs prior to neurodegeneration. Several lipid markers have been shown to predict prognosis in ALS. Sphingolipids are complex lipids enriched in the central nervous system and are integral to key cellular functions including membrane stability and signalling pathways, as well as being mediators of neuroinflammation and neurodegeneration. This review highlights the metabolism of sphingomyelin (SM), the most abundant sphingolipid, and of its metabolite ceramide, and its role in the pathophysiology of neurodegeneration, focusing on MNDs. We also review published lipidomic studies in MNDs. In the 13 studies of patients with ALS, 12 demonstrated upregulation of multiple SM species and 6 demonstrated upregulation of ceramides. SM species also correlated with markers of clinical progression in five of six studies. These data highlight the potential use of SM and ceramide as biomarkers in ALS. Finally, we review potential therapeutic strategies for targeting sphingolipid metabolism in neurodegeneration.

Internationally, it is widely accepted that holistic care is as an integral part of the care for people with motor neurone disease (MND), and their informal carers. However the optimal role of generalist and specialist palliative care, and how it integrates with specialist neurology services, is not fully established. Using a qualitative approach we sought to examine end of life care for people with MND in Northern Ireland, and the role of specialist and generalist palliative care. Qualitative study involving a convenience sample of 13 bereaved carers recruited using the Northern Ireland MND Register. Data collection consisted of semi-structured interviews with the bereaved carers of patients who had died 3–24 months previously with a diagnosis of MND. Data were analysed using thematic analysis. Findings illuminated variations in relation to the levels of holistic care provided to this cohort of patients. Unmanaged respiratory and psychological symptoms caused perceived distress amongst patients. Participants’ experiences additionally highlighted reluctance amongst patients with MND to engage with services such as specialist palliative care. Conversely, for those who received input from specialist palliative care services carers portrayed these services to be of great benefit to the patient. Patients with MND in Northern Ireland may have many unmet holistic care needs. Key areas that require particular focus in terms of service development include neuromuscular respiratory physiotherapy and psychological services for patients. Future research must explore an optimal model of holistic care delivery for patients with MND and how this can be effectively integrated to best meet this patient cohorts palliative care needs.

The aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed.

Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient. Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient. Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient. Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient. Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient. Providing a cutting-edge profile of research progress in this important field of study, Cholinergic Mechanisms: Function and Dysfunction contains a compilation of the proceedings of the Eleventh ISCM, held in St. Moritz, May 2002. Bringing together 250 contributors from 30 countries, the book presents a comprehensive picture of the cholinergic field. It provides a survey of current understanding of molecular, pharmacological, toxicological, behavioral, and clinical aspects of the cholinergic system. This volume offers a state-of-the-art account of progress in the field from the molecule in the test tube through the cell and the synapse, to the organism and the patient.