Unsolicited written narratives as a methodological genre in terminal illness: challenges and limitations

Stories about illness have proven invaluable in helping health professionals understand illness experiences. Such narratives have traditionally been solicited by researchers through interviews and the collection of personal writings, including diaries. These approaches are, however, researcher driven; the impetus for the creation of the story comes from the researcher and not the narrator. In recent years there has been exponential growth in illness narratives created by individuals, of their own volition, and made available for others to read in print or as Internet accounts. We sought to determine whether it was possible to identify such material for use as research data to explore the subject of living with the terminal illness amyotrophic lateral sclerosis/motor neuron disease—the contention being that these accounts are narrator driven and therefore focus on issues of greatest importance to the affected person. We encountered and sought to overcome a number of methodological and ethical challenges, which is our focus here

Defective axonal transport in motor neuron disease

Several recent studies have highlighted the role of axonal transport in the pathogenesis of motor neuron diseases. Mutations in genes that control microtubule regulation and dynamics have been shown to cause motor neuron degeneration in mice and in a form of human motor neuron disease. In addition, mutations in the molecular motors dynein and kinesins and several proteins associated with the membranes of intracellular vesicles that undergo transport cause motor neuron degeneration in humans and mice. Paradoxically, evidence from studies on the legs at odd angles (Loa) mouse and a transgenic mouse model for human motor neuron disease suggest that partial limitation of the function of dynein may in fact lead to improved axonal transport in the transgenic mouse, leading to delayed disease onset and increased life span

Quo vadis motor neuron disease?

Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, is a relentlessly progressive neurodegenerative condition that is invariably fatal, usually within 3 to 5 years of diagnosis. The aetio-pathogenesis of MND remains unresolved and no effective treatments exist. The only Food and Drug Administration approved disease modifying therapy is riluzole, a glutamate antagonist, which prolongs survival by up to 3 mo. Current management is largely symptomatic/supportive. There is therefore a desperate and unmet clinical need for discovery of disease mechanisms to guide novel therapeutic strategy. In this review, we start by introducing the organizational anatomy of the motor system, before providing a clinical overview of its dysfunction specifically in MND. We then summarize insights gained from pathological, genetic and animal models and conclude by speculating on optimal strategies to drive the step change in discovery, which is so desperately needed in this arena

Motor neuron disease in blacks

A series of 86 black, Indian and white patients with motor neuron disease were analysed retrospectively. Although the material does not allow statistically valid conclusions, there are sufficient cases among blacks to allow two prima facie observations in this population group: (i) motor neuron disease has an earlier age of onset than in whites and Indians; and (ii) more patients come from peripheral and rural areas than would be expected in prevailing circumstances.S Af Med J 1989; 76: 155-15

Baş düşmesi ile prezente olan motor nöron hastalığı

Motor nöron hastalığı, yutma, yürüme, konuşma ve nefes alma gibi işlevlerden sorumlu olan istemli kasları innerve eden motor nöronların tutulumu ile karakterize progresif nörolojik bir hastalıktır. En sık görülen formu amyotrofik lateral sklerozdur. Nörolojik muayene bulguları üst ve alt motor nöron dejenerasyonunu gösterir. Hastalığın tanısı için spesifik bir biyolojik marker bulunmamaktadır. Klinik özellikler elektromiyografik bulgularla birleştirilerek tanı konur. Literatürde az sayıda atipik prezentasyonlu motor nöron hastalığı olgusu bulunmaktadır. Bu yazıda boyun kaslarında progresif güçsüzlükle başlayan atipik bir motor nöron olgusu sunulmuştur.Motor neuron diseases are a group of progressive neurological disorders that destroy motor neurons that control voluntary muscle activity such as swallowing, walking, speaking and breathing. The common form of motor neuron disease is amyotrophic lateral sclerosis. Neurological examination presents specific signs associated with upper and lower motor neuron degeneration. In the absence of any biological marker, the diagnosis of motor neuron disease is based on clinical features, combined with the results of electromyography. Some patients of motor neuron disease with atypical presentation have been reported in the literature. We presented here a case of motor neuron disease with atypical presentation who had progressive weakness of the neck muscles

Mobility Improvements After a High-cadence Dynamic Cycling Intervention in an Individual with Motor Neuron Disease: A Case Study

International Journal of Exercise Science 14(3): 791-801, 2021. Previous exercise studies in individuals with motor neuron disease have shown some positive benefits but the stress of regular exercise could result in overuse weakness in this population. The purpose of this case study is to determine the efficacy, and tolerability of a high-cadence dynamic cycling intervention in an individual with motor neuron disease. A 67-year-old male with significant lower extremity weakness and a diagnosis of idiopathic motor neuron disease completed six 30-minute sessions of high cadence dynamic cycling over a two-week period using a custom-built motorized ergometer with the motor speed set at 80 revolutions per minute. This intervention resulted in an 80.4 m increase in walking distance during the six-minute walk test (21% increase), with a lower rating of perceived exertion than at baseline. Amyotrophic Lateral Sclerosis Functional Rating Scale- Revised scores improved slightly (2.4%) suggesting that the intervention was tolerated, and it did not compromise the participant’s physical function. These data show that this intervention can improve mobility, is well-tolerated and minimizes the risk of overuse weakness in an individual with motor neuron disease

Frontostriatal deficit in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS)

So far, cognitive derangements in MND/ALS have not been widely studied. Nevertheless, it seems that in subgroups of patients cognitive functions are impaired in different degree, so that often at least two sub-types of the syndrome are reported: Motor Neuron Disease/Amyotrophic Lateral Sclerosis/Dementia Syndrome (MND/ALS/DS) and Motor Neuron Disease/Amyotrophic Lateral Sclerosis/ Aphasia Syndrome (MND/ALS/AS. A third subtype showing both symptoms of cognitive impairment may be identified in subgroups of patients and denominated Motor Neuron Disease/Amyotrophic Lateral Sclerosis/Dementia-Aphasia Syndrome (MND/ALS/DAS). Frontostriatal system is reported as a network heavily damaged in MND/ALS/DS, MND/ALS/AS, MND/ALS/DAS. The system is plausibly responsible of motor skills and verbs production, hence to become aware of a possible frontostriatal deficit in subgroup of MND/ALS patients might consent us to link at the brain level (motor) action and verbs and possibly ideomotor praxia and verbs. We have used Goal-Oriented Perception Task (GOPT) and Action Fluency Task (AFT) in order to detect with some accuracy impairments related to gestaltic analysis directed toward a goal, and verb retrieval deficits possibly underlying executive system dysfunction that destabilizes the ability to mentally coordinate the information associated with a verb. These tests should consent to detect possible frontostriatal derangements. We have tested 10 MND/ALS patients and 10 healthy subjects matched fore age, sex and laterality. AFT showed that 3 out of 6 patients are heavily impaired in this test (6.3 (mean) verbs generated vs 13.3 of the control group). GOPT detected a remarkable impairment in all patients: p=0.0021 (grammatical side), p=0.0002 (perceptual side). Reported frontostriatal deficit in MND/ALS seems confirmed by this study, and probably it is more easily detected by GOPT than by AFT

Non-motor symptoms in motor neuron disease:Prevalence, assessment and impact

People with motor neuron disease often experience non-motor symptoms that may occur secondary to, or distinct from, motor degeneration and that may significantly reduce quality of life, despite being under-recognized and evaluated in clinical practice. Non-motor symptoms explored in this population-based study include pain, fatigue, gastrointestinal issues, poor sleep, low mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction. People registered on the Clinical Audit Research and Evaluation of motor neuron disease platform, the Scottish Motor Neuron Disease Register, were invited to complete a questionnaire on non-motor symptoms and a self-reported Amyotrophic Lateral Sclerosis Functional Rating Scale. The questionnaire comprised a pre-defined list of 11 potential non-motor symptoms, with the opportunity to list additional symptoms. A total of 120 individuals participated in this cross-sectional study, a 39% response rate of those sent questionnaires (n = 311); 99% of participants recruited (n = 120) experienced at least one non-motor symptom, with 72% (n = 120) reporting five or more. The symptoms most often reported were pain and fatigue (reported by 76% of participants, respectively). The symptoms reported to be most impactful were gastrointestinal issues (reported as ‘severe’ by 54% of participants who experienced them), followed by pain and problematic saliva (51%, respectively). Lower Amyotrophic Lateral Sclerosis Functional Rating Scale scores, indicating more advanced disease and being a long survivor [diagnosed over 8 years ago; Black et al. (Genetic epidemiology of motor neuron disease-associated variants in the Scottish population. Neurobiol Aging. 2017;51:178.e11-178.e20.)], were significantly associated with reporting more symptoms; 73% of respondents were satisfied with the frequency that non-motor symptoms were discussed in clinical care; 80% of participants indicated they believe evaluation of non-motor symptom is important to include as outcomes in trials, independent of their personal experience of these symptoms. The preferred method of assessment was completing questionnaires, at home. The overwhelming majority of people with motor neuron disease report non-motor symptoms and these frequently co-occur. Pain, fatigue, gastrointestinal issues, sleep, mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction are prevalent. People with motor neuron disease who had worse physical function and those who were long survivors were more likely to report more symptoms. Where reported, these symptoms are frequent, impactful and a priority for people with motor neuron disease in clinical care and trial design

Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease

Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and α motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament-binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model