The Association Between Benign Fasciculations and Health Anxiety: A Report of Two Cases and a Systematic Review of the Literature.

BACKGROUND: Benign fasciculation syndrome (BFS) is characterized by persistent spontaneous contractions of muscle fibers in the absence of a pathological cause. Patients with BFS often have concerns around having motor neuron disease, in some cases fulfilling the criteria for health anxiety disorder. Research on how BFS and health anxiety relate to one another and how they should be optimally managed together is sparse. OBJECTIVE: We report two cases of BFS associated with health anxiety. We also review the literature on the association between BFS and health anxiety. METHODS: We systematically reviewed the literature using MEDLINE, Embase, PsycINFO, and OpenGrey for studies investigating benign fasciculations and anxiety up to August 2018. RESULTS: Both cases were successfully treated for health anxiety disorder with cognitive-behavioral therapy (CBT) and antidepressant medication. We identified eight studies that met the inclusion criteria, describing a total of 384 patients. Most studies were of moderate quality. Patients with BFS tended to be male and in their 30s or 40s. There was an overrepresentation of clinicians. Anxiety symptoms were common and frequently coexisted alongside fasciculations. Health anxiety was overwhelmingly focused around motor neuron disease. CONCLUSION: A proportion of individuals with BFS experience anxiety around having motor neuron disease-to the point of developing health anxiety disorder. A bidirectional relationship may exist between BFS and health anxiety disorder. Clinicians should be alert to the possibility of health anxiety disorder in patients with BFS and have a low threshold to refer for psychiatric assessment. There is support for the role of psychological therapy, especially CBT, as well as pharmacotherapy, in the form of antidepressant medication. In severe or treatment-refractive cases, combined treatment may be indicated.

No evidence for a large difference in ALS frequency in populations of African and European origin: a population based study in inner city London.

Abstract Previous studies have suggested a lower incidence of ALS in people of African origin. We used a population based register in an urban setting from inner city London postcodes where there is a large population of people of African ancestry to compare the frequency of ALS in people of European and African origin. Population statistics stratified by age, gender and ethnicity were obtained from the 2001 census. Incidence and prevalence were calculated in each ethnic group. Results showed that in a population of 683,194, of which 22% were of African ancestry, 88 individuals with ALS were identified over a seven-year period, including 14 people with African ancestry. The adjusted incidence in people of African ancestry was 1.35 per 100,000 person-years (95% CI 0.72-2.3) and in those of European ancestry 1.97 per 100,000 person-years (95% CI 1.55-2.48). In conclusion, in this small population based study we could not detect a difference in rates of ALS between people of African ancestry and those of European ancestry.

Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020-2116.

Objective: To model the effects of demographic change under various scenarios of possible future treatment developments in ALS. Methods: Patients diagnosed with ALS at the King's College Hospital Motor Nerve Clinic between 2004 and 2017, and living within the London boroughs of Lambeth, Southwark, and Lewisham (LSL), were included as incident cases. We also ascertained incident cases from the Canterbury region over the same period. Future incidence of ALS was estimated by applying the calculated age- and sex-specific incidence rates to the UK population projections from 2020 to 2116. The number of prevalent cases for each future year was estimated based on an established method. Assuming constant incidence, we modelled four possible future prevalence scenarios by altering the median disease duration for varying subsets of the population, to represent the impact of new treatments. Results: The total number of people newly diagnosed with ALS per year in the UK is projected to rise from a baseline of 1415 UK cases in 2010 to 1701 in 2020 and 2635 in 2116. Overall prevalence of ALS was predicted to increase from 8.58 per 100,000 persons in 2020 to 9.67 per 100,000 persons in 2116. Halting disease progression in patients with C9orf72 mutations would yield the greatest impact of the modelled treatment scenarios, increasing prevalence in the year 2066 from a baseline of 9.50 per 100,000 persons to 15.68 per 100,000 persons. Conclusions: Future developments in treatment would combine with the effects of demographic change to result in more people living longer with ALS.

A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis.

Failure to clear oral secretions can be debilitating for patients with amyotrophic lateral sclerosis (ALS), but the treatment of this symptom is poorly defined and there is no consensus on best practice. The objective of this study was to identify the treatments that are commonly prescribed, and to describe how experienced clinicians manage a patient with treatment resistant symptoms. Twenty-three clinicians were approached, of which 19 from 16 centres across the UK provided case report forms for a total of 119 ALS patients identified as having problematic oral secretions. The use of five anticholinergics, salivary gland botulinum toxin injections, conservative management approaches and carbocisteine were reported. Of the 72 patients who were evaluated following the initiation of a first anticholinergic, 61% had symptomatic improvement. Only 19% of patients achieved symptomatic improvement with the use of an alternative anticholinergic when an initial anticholinergic achieved no symptomatic improvement. Problems with thick and thin secretions often coexisted, with 37% of patients receiving treatment for both types of problem. In conclusion, a variety of treatment options are employed by expert clinicians for problematic oral secretions in ALS patients. The variation in management highlights the need for further prospective research in this area.

Evidence of an environmental effect on survival in ALS.

Amyotrophic lateral sclerosis (ALS, motor neuron disease) is a neurodegenerative disorder of motor neurons leading to paralysis and eventual death by respiratory failure. Median survival is 2-3 years. Susceptibility genes, environmental triggers and disease related prognostic factors have been established, but environmental effects on survival are yet to be investigated. We analysed survival in the South-East England ALS register (SEALS register). Kaplan-Meier and Cox regression analyses were used to investigate survival in London, coastal and rural areas according to postcode at diagnosis. Results showed that there were 933 cases of ALS identified in the catchment area during the study period (1994-January 2012). Cox regression demonstrated a highly significant model for survival with significant protective variables: coastal residency, riluzole use and younger age at onset. Significantly worse survival was associated with London residency, older age as well as definite and probable El Escorial classifications. In conclusion, these findings suggest the possibility of an environmental effect on survival in ALS.

The evaluation of pain in amyotrophic lateral sclerosis: a case controlled observational study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive paralysis. ALS is complicated by a number of non-motor symptoms including pain. Pain in ALS has been poorly studied and poorly managed. This study aimed to collate information regarding pain in ALS using standardized pain questionnaires. Forty-two patients with ALS participated in the study. Control subjects included 41 age-matched healthy volunteers and 42 age-matched patients with neurological conditions other than ALS. Data on pain were collected using the The Brief Pain Inventory and The painDetect Questionnaire. Eighty-five percent of subjects with ALS reported pain versus 50% of neurology clinic controls and 35% of healthy controls (p < 0.01). Pain in ALS included cramping, aching, tiring, sharp and tender, and was non-neuropathic. Pain impacted significantly on mood, general activity, relationships and general enjoyment of life. Fifty-four percent of people with painful ALS used regular analgesia and 29% regular opioids. Other non-motor symptoms suffered included tiredness, constipation, urinary problems, itching and drowsiness. In conclusion, these data support the fact that pain is a significant symptom in ALS which impacts on quality of life. These data can be used to educate clinicians and patients to promote better multidisciplinary management of ALS symptoms and a better quality of life.

Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.

BACKGROUND: Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. METHODS: We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. FINDINGS: We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5-5·0), with similar estimates for men (4·6, 4·3-4·9) and women (5·0, 4·5-5·5). INTERPRETATION: A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. FUNDING: UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).

Management of sialorrhoea in motor neuron disease: a survey of current UK practice.

Our objective was to better understand UK-wide practice in managing sialorrhoea in motor neuron disease among specialist clinicians. We used a survey of neurologists in the UK with a special interest in motor neuron disease designed to establish clinicians' attitudes towards treatment options and resources for sialorrhoea management. Twenty-three clinicians replied, representing 21 centres. Sixteen centres were specialist MND Care Centres. Clinicians estimated seeing a total of 1391 newly diagnosed patients with MND in 2011. One hundred and ninety-three patients were described. Forty-two percent of patients reviewed in clinicians' last clinic had sialorrhoea and 46% of those with sialorrhoea had uncontrolled symptoms. Clinicians' preferred drugs were hyoscine patches, amitriptyline, carbocisteine and botulinum toxin. Botulinum toxin was used in 14 centres. Risk of dysphagia and staff skills were identified as the main barriers to botulinum toxin use. This survey suggests that there may be as many as 1700 patients with MND in the UK who have symptoms of sialorrhoea and that symptoms may be poorly controlled in nearly half. Treatment strategies varied, reflecting the lack of evidence based guidelines. The use of specialist treatments was influenced by local infrastructure. This study highlights the need for further work to develop evidence based guidance.

Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis.

RATIONALE AND OBJECTIVES: There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966-April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS: Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66-0.83), pooled sensitivity was 0.68 (95% CI: 0.62-0.75), and pooled specificity was 0.73 (95% CI: 0.66-0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION: Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.