This information is for health professionals and service providers.
Increasing weakness of bulbar, limb, thoracic and abdominal muscles due to the progressing degeneration of upper motor (UMN) and lower motor (LMN) neurons leads to a range of symptoms depending on the muscles impacted.
Weakness of limb, abdominal and neck muscles results in stiffness and immobility. This increasing weakness impacts comfort, independence and all aspects of daily living.
People with MND need support from the multidisciplinary team to help them manage their daily personal activities and to remain as independent and comfortable as possible:
Motor neurones do not transmit or modify pain signals, so the disease itself is not inherently painful. However, pain and discomfort in MND arise as complications of muscle weakness, stiffness and immobility. In addition, pain from pre-existing conditions such as arthritis may be exacerbated by muscle wasting.
Pain can significantly interfere with the quality of life of people with MND because of its impact on activity levels, mood, sleep, relationships, and general enjoyment of life.
The reported prevalence of pain in ALS varies from 15% to 85%. This large variability can be attributed to differences in definitions and measurements used to identify and quantify pain, and in study designs and settings. The clinical manifestation of pain in ALS varies extensively, which has been interpreted as variation depending on whether the mechanisms behind pain represent primary mechanisms or secondary consequences of motor degeneration. Pain can be acute or chronic, occurring in different stages of the disease. There is no typical localization of pain related to ALS, and pain could be localized to the head, neck or lumbar region, proximally and distally in the upper and lower extremities, or widespread. Reported pain intensity varies between studies from mild, to moderate, to severe, with indications of higher pain intensity in the last stage of the disease.
There is a need for health care professionals involved in the care of patients with MND to support patients’ opening up about their pain, and making sure that proper pain management strategies are provided. This should be done during the entire course of the disease, i.e., from diagnosis to the terminal stages. Since some participants in our study shared about their diminishment of pain symptoms, we propose that health care professionals should consciously validate the experience of pain and refer to their experiences of pain being a nuisance related to the disease. They should also offer information about the pain being possible to treat successfully with medication, by contrast to the possibility of curing the disease itself.
Non-pharmacological pain management strategies should also be considered, e.g., the adaptation of auxiliary means and orthotic devices with the explicit goal of obtaining pain relief. Today these means are often adequate in support of physical function, whereas adaptation for pain relief could be improved. Strategies for activity planning are also proposed to find means that facilitate the performance of necessary yet painful activities as much as possible, and thereby enhance possibilities for persons with MND to engage in personally prioritized activities of importance for individual quality of life (Åkerblom et al 2020).
Patients with ALS tend to experience nociceptive pain rather than neuropathic pain. Common causes of pain in patients with spinal-onset ALS include muscle cramps secondary to dysfunction of motor units, and shoulder pain either secondary to overuse or from traction on peri-articular structures from the unsupported weight of the arm due to weakness and wasting of the shoulder girdle musculature. Patients should use armrests on chairs and wheelchairs, and may require a sling that supports the forearm, including the elbow.
Pharmaceutical options include paracetamol, anti-inflammatory agents, opioids, gabapentin, pregabalin, tricyclic antidepressants, intra-articular steroid injections and transcutaneous electrical nerve stimulation (TENS). Second-line agents include mexiletine and levetiracetam; however, these require initiation and monitoring by an experienced team (Lau et al 2018).
Drug therapy for pain
There is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND (Ng et al 2017).
More than half of those with ALS experience pain and it impacts on quality of life and a small number experience other sensory symptoms but no trials in ALS have been conducted (Hobson and McDermott 2016).
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 (Wallace et al 2014).
Cramps are common early in the disease course. Ongoing and careful assessment and review is required to determine the best treatment options for the person living with MND.
Treatment for cramps
There is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:
– memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate‐quality evidence);
– vitamin E may have little or no effect (low‐quality evidence); and
– the effects of L‐threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.
The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects (Ng et al 2017).
Cramps are common in ALS but Cochrane review of trials of various treatments including one randomised controlled trial of tetrahydrocannabinol reported no evidence to recommend any particular treatment. An open label study of levetirecetam in 20 patients has reported a reduction in cramp frequency and severity. Quinine is the most commonly used therapy for cramps but use for this indication is restricted in the United States because of reports of rare but serious haematological and cardiac events (665 serious events and 93 deaths between 1969 and 2006).A Cochrane review of quinine in patients with various causes of cramp found moderate evidence that quinine was safe and effective. The side effects of quinine are dose dependent and it is possible that low dose quinine used in cramps may not be associated with these side┽effects but the studies included in the review may be too small to detect very rare events. In the absence of an effective alternative guidance from the American Academy of Neurology recommends that quinine only be used as a last resort (Hobson and McDermott 2016).
Cramps may be a troublesome symptom, particularly at night. A single randomized controlled trial with tetrahydrocannnabinol failed to show efficacy in patients with ALS with moderate to severe cramps (Class I). Levetiracetam was beneficial in an open-label small pilot study (Class IV). Quinine sulphate has been banned by the FDA because of safety concerns. However, a recent Cochrane Review in non-ALS cramps found quinine sulphate to be effective with no difference serious adverse events between the placebo and active drug. Treatments such as massage, physical exercise, hydrotherapy in heated pools, carbamazepine, diazepam, phenytoin and verapamil have been tried, but there are no controlled studies in ALS (Andersen et al 2012).
A coordinated team approach with a physiotherapist, occupational therapist and medical practitioner is essential to determine the relative role of medication, regular physiotherapy e.g. passive stretching of limbs and optimal positioning in bed and chair.
Treatment for spasticity
It is uncertain whether an endurance‐based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available (Ng et al 2017).
Spasticity causes pain and loss of function and can be exacerbated by factors such as infection and poor positioning. There is no evidence to recommend one management strategy over another. Muscle relaxants can exacerbate muscle weakness and their sedating side-effects are often intolerable. One randomised controlled trial of prescribed exercise in 25 patients observed small improvements in disability and spasticity. In observational studies intrathecal baclofen improved symptoms and quality of life in patients where oral medication has failed (Hobson and McDermott 2016).
Physical therapy is the mainstay of treatment of spasticity in ALS and has been found effective (Class III). Other interventions such as hydrotherapy, heat, cold, ultrasound, electrical stimulation, chemodenervation and in rare cases surgery have been used, although no controlled studies in ALS exist. In patients with ALS, intractable spasticity, and associated pain, intrathecal baclofen was more effective than oral medication and greatly improved patients’ quality of life (Class IV). Although not formally tested in ALS, in clinical practice, gabapentin (900–2400 mg daily), tizanidine (6–24mg daily), memantine (10–60mg daily), dantrolene (25–100mg daily), tetrazepam (100–200mg daily) and diazepam (10–30mg daily) have been used. Botulinum toxin A has successfully been used to treat trismus and stridor in single cases (Andersen et al 2012).
People living with MND and health providers commonly question the effect of exercise on MND. While exercise generally has many benefits, there is little research to ascertain its benefits to people living with MND. In addition, some studies have raised concern about intense kinds of physical activities and MND.
The recent systematic review, referenced below, found that therapeutic physical activity could contribute to slowing down the deterioration of muscles in the body of people with MND. Physical activity helps to counteract the muscle weakness caused by the degeneration of nerves from MND by strengthening healthy nerves and muscles. Daily activities can become easier and quality of life may improve, particularly in the medium to long term.
Research also suggests that physical activity may:
Regular assessment and review by the physiotherapist and occupational therapist is recommended for:
The multidisciplinary team can also advise on a program of tailored physical activity to address:
Therapeutic physical exercise could help to slow down the deterioration of the musculature of people with ALS, thus facilitating their performance of activities of daily living and, therefore, maintaining the levels of their scores on the ALSFRS-R functionality scale, especially in the medium and long terms, compared to those in ALS patients with mostly passive treatments.
The survival of patients did not improve in relation to a therapeutic physical exercise programme, although their respiratory muscles did improve the levels measured in the FVC, which leads to an improvement in their quality of life until the end of their disease.
Carrying out a treatment that includes physical activity in patients with ALS helps to counteract the muscle weakness caused by the degeneration of poorly innervated cells, as it strengthens healthy cells, and these patients obtained better results in the 6MWT after several months of rehabilitation.
Regarding the type of exercise, it could be inferred that moderate intensity and not very high frequencies (two sessions/week), combining strength and aerobic resistance, could be the best option to observe improvements in patients with ALS and prevent the onset of fatigue in these patients, since their FSS values may increase with more intense therapies (Ortega-Hombrados et al 2021).
Until now, the role of physical exercise in ALS pathology has been controversial. Some epidemiological studies have suggested that people practicing intense physical activity, like professional soccer or football players, have a higher risk of developing the disease. This could be due to hard and prolonged exercise inducing inflammation, oxidative stress, and glutamate excitotoxicity in MNs, all mechanisms involved in their degeneration. On the other hand, some evidence has shown the protective effect of mild physical exercise in ALS (Maugeri and D’Agata 2020).
There is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low‐quality evidence, N = 43) (Ng et al 2017).
The impact of exercise in MND displays an interesting dichotomy. On one hand, it has been suggested by epidemiological studies that the incidence of MND may be associated with the extent of exercise undertaken prior to the onset of disease. An example of this includes the possibility of an increased frequency of MND in professional sportspeople such as soccer players. However, after the onset of MND, structured exercise programmes may improve function and does not appear to be harmful. This suggests that physical fitness is a marker of corticomotoneuronal system vulnerability, but that exercise itself is not intrinsically harmful (Simon et al 2015).
Muscle weakness is very common in people with amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND). A weak muscle can be damaged if overworked because it is already functioning close to its maximal limits.
Because of this, some experts have discouraged exercise programs for people with ALS. However, if a person with ALS is not active, deconditioning (loss of muscle performance) and weakness from lack of use occurs, on top of the deconditioning and weakness caused by the disease itself. If the reduced level of activity persists, many organ systems can be affected and a person with ALS can develop further deconditioning and muscle weakness, and muscle and joint tightness may occur leading to contractures (abnormal distortion and shortening of muscles) and pain. These all make daily activities harder to do.
Despite the high incidence of muscle weakness in individuals with amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), the effects of exercise in this population are not well understood.
The only studies detected were too small to determine to what extent strengthening exercises for people with ALS are beneficial, or whether exercise is harmful. There is a complete lack of randomised or quasi-randomised clinical trials examining aerobic exercise in this population. More research is needed (Dal Bello-Haas and Florence 2013).
See table 1: symptom management recommendations
National Institute for Health and Clinical Excellence (2016) NICE Guideline: Motor Neurone Disease Assessment and Management – see recommendation:
1.8 Managing Symptoms: Pharmacological Treatments for muscle problems and exercise programmes
Being a syndrome with low incidence and short survival, most recommendations are good clinical practice principles (GCPPs) based on the consensus of experts in the field of ALS. Further randomized and double‐blind clinical trials are urgently needed to improve the management of ALS.
MND Aware e-training program MND Hub – online training course for health professionals and service providers developed by MND NSW – Sessions 15 and 21: Symptom Management – Movement and Joints and Wellbeing needs - Daily living and mobility
MND Association blog post, June 2021, Physical exercise as a risk factor for MND – is it in our genes?
International Alliance of ALS/MND Associations,18th Allied Professionals Forum, 2020:
International Alliance of ALS/MND Associations,17th Allied Professionals Forum, Perth 2019:
MND Association England, Wales and Northern Ireland, Pain in MND
ALS Canada, Facts about pain and ALS
MND Australia Fact Sheet series for people living with MND:
ALS TDI- ALS Town Hall: Exercise and MND
Health Talk - healthtalk.org - stories collected by academic researchers who interview people in their own homes, using their own words: