Is farming a risk factor for motor neurone disease?

Farming and incidence of motor neuron disease: French nationwide study

Kab S, Moisan F, Elbaz A

Eur J Neurol 2017 (Epub ahead of print).



The association of farming with motor neuron disease (MND) is unclear, with conflicting studies. We performed a French nationwide study of the association of farming with MND incidence, and compared findings with those for Parkinson’s disease (PD), which has been shown to be more frequent in farmers.


We used the French national health insurance and hospital discharge databases to identify MND/PD incident cases. The Mutualité Sociale Agricole (MSA) guarantees health insurance for farmers and agricultural workers. We compared the incidence of MND (2010-2014) and PD (2011-2012) in MSA farmers, MSA workers and non-MSA affiliates, and estimated relative risks (RRs) and 95% confidence intervals (CIs). Probabilistic sensitivity analyses were used for external smoking adjustment.


Analyses relied on 8931 MND (MSA, 9%) and 45 409 PD (MSA,11%) cases. There was a trend towards higher MND incidence in MSA farmers compared with non-MSA affiliates (RR,1.08; 95% CI,0.99-1.18) and MSA workers (RR, 1.13; 95% CI, 0.97-1.31) that strengthened after smoking adjustment (if associated with MND). PD incidence was higher in MSA farmers than non-MSA affiliates (RR, 1.13; 95% CI, 1.08-1.17) and MSA workers (RR, 1.10; 95% CI, 1.02-1.18); this association remained after smoking adjustment (RR, 1.09; 95% CI, 1.05-1.14).


This French nationwide study suggested an association between farming and MND, and confirmed higher PD incidence in farmers in France, a country with high pesticide use.

This reference is included in the neurochecklist:

Motor neurone disease (MND): risk factors

Abstract link

By Vincent van Gogh – own photo in the Kröller-Müller museum, Public Domain, Link

Will edaravone improve the outcome of motor neurone disease?

Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis

Sawada H

Expert Opin Pharmacother 2017; 18:735-738.



Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid.

Areas covered:

Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed. In all trials, the primary outcome measure was the changes in scores on the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of patients.

Expert opinion:

The phase II open label trial suggested that edaravone is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the cerebrospinal fluid. One of the two randomized controlled trials showed beneficial effects in ALSFRS-R, although the differences were not significant.

The last trial demonstrated that edaravone provided significant efficacy in ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted. Eligibility was restricted to patients with a relatively short disease duration and preserved vital capacity. Therefore, combination therapy with edaravone and riluzole should be considered earlier.

You may also check

Writing Group.; Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2017; 16:505-512.

Both references are included in the neurochecklist:

Motor neurone diseases (MND): main treatments

Abstract link 1

Abstract link 2

By BruceBlausOwn work, CC BY-SA 4.0, Link

What is the benefit of meditation training in MND?

Meditation training for people with amyotrophic lateral sclerosis: a randomized clinical trial.

Pagnini F, Marconi A, Tagliaferri A, et al.

Eur J Neurol 2017; 24:578-586.



Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population.


A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life. Adults who received a diagnosis of ALS within 18 months were randomly assigned either to usual care or to an 8-week meditation training based on the original mindfulness-based stress reduction programme and tailored for people with ALS. Quality of life, assessed with the ALS-Specific Quality of Life Revised scale, represented the primary outcome, whilst secondary outcomes included anxiety and depression, assessed with the Hospital Anxiety and Depression Scale, and specific quality of life domains. Participants were assessed at recruitment and after 2, 6 and 12 months. The efficacy of the treatment was assessed on an intention-to-treat basis of a linear mixed model.


A hundred participants were recruited between November 2012 and December 2014. Over time, there was a significant difference between the two groups in terms of quality of life (β = 0.24, P = 0.015, d = 0.89). Significant differences between groups over time were also found for anxiety, depression, negative emotions, and interaction with people and the environment.


An ALS-specific meditation programme is beneficial for the quality of life and psychological well-being of people with ALS.

This reference is now cited in the neurochecklist:

Motor neurone disease (MND): symptomatic care

Abstract link

By Moyan Brenn from Anzio, Italy – Meditation, CC BY 2.0, Link


Is motor neurone disease in HIV a treatable disorder?

 HIV-associated motor neuron disease. HERV-K activation and response to antiretroviral therapy

Bowen LN, Tyagi R, Li W, et al.

Neurology 2016; 87:1756-1762.



To determine whether there is activation of human endogenous retrovirus K (HERV-K) in amyotrophic lateral sclerosis in HIV infection and whether it might respond to treatment with antiretroviral drugs.


In this case series, we present 5 patients with HIV infection who subsequently developed motor neuron disease involving both upper and lower motor neurons. We monitored HERV-K levels in plasma of 4 of these patients.


Three patients who received antiretroviral therapy had reversal of symptoms within 6 months of onset of neurologic symptoms and the other 2 had slow neurologic progression over several years. Three patients in whom the levels were measured at onset of neurologic symptoms showed elevated HERV-K levels that responded to optimization of antiretroviral therapy for CNS penetration.


Thus, motor neuron disease in individuals with HIV infection may a treatable entity, but early treatment with CNS-penetrating antiretroviral therapy may be necessary. Monitoring of HERV-K levels may help guide treatment.

This reference is now included in the neurochecklists:

Motor neurone disease (MND): risk factors

HIV associated neurological infections



Abstract link

By US National Institute of Health (redrawn by en:User:Carl Henderson) - US National Institute of Health (redrawn by en:User:Carl Henderson), Public Domain, Link
By US National Institute of Health (redrawn by en:User:Carl Henderson) – US National Institute of Health (redrawn by en:User:Carl Henderson), Public Domain, Link

What determines the poor prognosis of C9orf72 MND?

 C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis

Rooney J, Fogh I, Westeneng HJ, et al.

JNNP 2016; pii: jnnp-2016-314093 (Epub ahead of print).



The C9orf72 repeat expansion has been reported as a negative prognostic factor in amyotrophic lateral sclerosis (ALS). We have examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset.


C9orf72 status and demographic/clinical data from 4925 patients with ALS drawn from 3 prospective ALS registers (Ireland, Italy and the Netherlands), and clinical data sets in the UK and Belgium. Flexible parametric survival models were built including known prognostic factors (age, diagnostic delay and site of onset), gender and the presence of an expanded repeat in C9orf72. These were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data (IPD) meta-analysis was used to estimate HRs for results of particular importance.


457 (8.95%) of 4925 ALS cases carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival HR of 1.36 (1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion was being driven by spinal onset males (HR 1.56 (95% CI 1.25 to 1.96).


This study represents the largest combined analysis of the prognostic characteristics of the C9orf72 expansion. We have shown for the first time that the negative prognostic implication of this variant is driven by males with spinal onset disease, indicating a hitherto unrecognised gender-mediated effect of the variant that requires further exploration.

This reference is now included in the neurochecklist:

Motor neurone disease (MND): familial types


Abstract link

By U.S. National Library of Medicine -, Public Domain, Link
By U.S. National Library of Medicine –, Public Domain, Link

How often does depression precede the onset of MND?

Depression in amyotrophic lateral sclerosis

 Roos E, Mariosa D, Ingre C, et al.

Neurology 2016; 86:2271-2277.



To examine the relative risk of depression among patients with amyotrophic lateral sclerosis (ALS), both in terms of depression diagnosis and use of antidepressant drugs, before and after diagnosis.


We conducted a nested case-control study including 1,752 patients with ALS diagnosed from July 2005 to December 2010 and 8,760 controls based on the Swedish national health and population registers, to assess the associations of depression diagnosis and use of antidepressant drugs with a subsequent risk of ALS. We further followed the patients with ALS after diagnosis to estimate the association of an ALS diagnosis with the subsequent risk of depression and use of antidepressant drugs.


Before diagnosis, patients with ALS were at higher risk of receiving a clinical diagnosis of depression compared to controls (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.3-2.3), and the highest risk increase was noted during the year before diagnosis (OR 3.5, 95% CI 2.1-5.6). Patients with ALS also had a highly increased risk of depression within the first year after diagnosis (hazard ratio 7.9, 95% CI 4.4-14.3). Antidepressant use was more common in patients with ALS than in controls, especially during the year before (OR 5.8, 95% CI 4.5-7.5) and the year after (hazard ratio 16.1, 95% CI 11.5-22.6) diagnosis.


Patients with ALS are at higher risk of depression diagnosis and use of antidepressant drugs both immediately before and after diagnosis.


Also check up

Psychiatric disorders prior to amyotrophic lateral sclerosis.

Turner MR, Goldacre R, Talbot K, Goldacre MJ.

Ann Neurol 2016; 80:935-938.

Does smoking influence the prognosis of MND?

Influence of cigarette smoking on ALS outcome: a population-based study

Calvo A, Canosa A, Bertuzzo D, et al.

JNNP 2016; 87:1229-1233.



To assess the prognostic influence of premorbid smoking habits and vascular risk profile on amyotrophic lateral sclerosis (ALS) phenotype and outcome in a population-based cohort of Italian patients.


A total of 650 patients with ALS from the Piemonte/Valle d’Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid cigarette smoking habits and chronic obstructive pulmonary disease (COPD) were collected at the time of diagnosis.


Current smokers had a significantly shorter median survival (1.9 years, IQR 1.2-3.4) compared with former (2.3 years, IQR 1.5-4.2) and never smokers (2.7 years, IQR 1.8-4.6) (p=0.001). Also COPD adversely influenced patients’ prognosis. Both smoking habits and CODP were retained in Cox multivariable model.


This study has demonstrated in a large population-based cohort of patients with ALS that cigarette smoking is an independent negative prognostic factor for survival, with a dose-response gradient. Its effect is not related to the presence of COPD or to respiratory status at time of diagnosis. The understanding of the mechanisms, either genetic or epigenetic, through which exogenous factors influence disease phenotype is of major importance towards a more focused approach to cure ALS.

This reference is now included in the neurochecklist:

Motor neurone disease (MND): outcome


Abstract link

Smoking. Philippa Willitts on Flikr.
Smoking. Philippa Willitts on Flikr.

Blog at

Up ↑