There is no cure for motor neurone disease, but symptom control is achievable and can improve quality of life.
Motor neurone disease (MND) is a neurodegenerative condition that affects the brain and spinal cord. It is thought that there are around 5,000 adults in the UK living with MND, the majority of whom are aged between 55 and 79 years. MND has unknown aetiology and is subdivided depending on the class of motor neurones affected (i.e. upper motor neurones [UMN] and lower motor neurones [LMN]) and the variety of symptoms present (see Table). As the disease progresses, the signs and symptoms become similar, irrespective of the initial MND type diagnosed. These symptoms include limb and torso muscle weakness, difficulty swallowing and speaking, and respiratory muscle weakness that leads to respiratory failure and death.
MND cannot be cured and ethical debates around assisted suicide, as the course and outcome of this disease can be extremely difficult for the patient and their relatives, have put a spotlight on the disease. However, symptom control is achievable to ensure optimum quality of life (QOL). A multidisciplinary team (MDT) approach is paramount in achieving this and the involvement of palliative care specialists is recommended from initial diagnosis in order to offer a holistic management approach, where the needs of the patient and relatives are met throughout the trajectory of the disease.
As part of a MDT, pharmacists can advise on the administration of medicines prescribed for the control of symptoms associated with MND. This article describes the holistic management of the most common symptoms encountered in MND and provides examples of how this is applied locally in the UK.
Common symptoms and their management
Problems with muscles and movement
Muscle weakness, muscle twitching, cramps and stiffness are all commonly experienced by people with MND.
First-line treatment is quinine bisulphate 300mg tablets at night. Since no formal trials have studied the nature of cramps in MND or the effect of medicine on cramps in this disease, evidence is based on quinine bisulphate use in muscle cramps regardless of cause. A meta-analysis of 23 trials demonstrated low-quality evidence that quinine (most commonly used dose of 300mg/day) reduced the number and days of muscle cramps, while moderate-quality evidence demonstrated that it reduced the intensity of cramps. The Medicines and Healthcare products Regulatory Agency advises that quinine should only be used when cramps are painful and persistent, and that use is periodically reviewed for side effects (e.g. abdominal pain and hearing impairment).
If quinine is ineffective or contraindicated, second-line treatment is baclofen 5mg twice or three times per day. If baclofen is not effective, not tolerated or contraindicated, consider tizanidine, dantrolene or gabapentin.
Baclofen, tizanidine, dantrolene or gabapentin can be considered to treat muscle stiffness, spasticity or increased tone in people with MND.
Physical exercise, such as stretching, which is adapted to the patient’s ability, can also help reduce stiffness and discomfort. Exercises will not strengthen the patient’s muscles, but will help to keep them as active as possible.
Physiotherapists can recommend exercises that help the patient maintain their posture and flexibility at initial stages of the disease, as well as exercises that focus on breathing as the patient approaches end of life. Occupational therapists can assess patients for wheelchair use, arm and neck supports, rise and recliner chairs, commodes and other equipment to aid activities around the house.
Difficulty in swallowing and weight loss
When prescribing medicines it is important to consider if the patient has dysphagia and is unable to swallow. Speech and language therapists (SALTs) will be able to provide advice on food and drink consistency, as well as appropriate body positioning during meals. Dietitians can help determine calorific intake and optimise nutritional supplements.
Surgically, a percutaneous endoscopic gastrostomy (PEG) is indicated when the patient is considered to be at high risk of aspiration, choking, malnutrition and dehydration. MND nutritional guidelines recommend PEG insertion once the patient experiences >10% weight loss and has a forced vital capacity (FVC) of >50% predicted for the patient’s age and height. A retrospective study of 150 dysphagic amyotrophic lateral sclerosis (ALS) patients demonstrated that PEG insertion increased overall survival by at least 6 months. A proportion of the patients studied who had successful PEG insertion had FVC <50% with short-term mortality (at one month) similar to that of patients with FVC >50%. They showed marginally higher medium-term mortality (at six months), but this was non-significant. In practice, a MDT approach is instrumental to assess and advise the patient on whether PEG insertion is appropriate and beneficial.
Also known as sialorrhoea, drooling occurs owing to poor handling of saliva and not necessarily owing to excess saliva production.
The anticholinergic treatment, hyoscine hydrobromide patch 1.5mg every 72 hours, as well as amitriptyline 10mg three times per day or atropine eye drops 0.5% or 1% two to four times per day sublingually, are recommended by national and European guidelines as first-line treatment options.
For patients with cognitive impairment, glycopyrronium is an alternative as its poor lipophilicity prevents its passage through the blood–brain barrier, resulting in minimal medication-induced drowsiness.
If first-line treatment for sialorrhoea is not effective, not tolerated or contraindicated, the National Institute for Health and Care Excellence (NICE) recommends botulinum toxin A administration in a specialist setting. In a systematic review, 7 out of 12 studies reported a statistically significant reduction in drooling after treatment with botulinum toxin A or B; however, none of the trials were specifically related to MND patients. The neurotoxin, which is used as an unlicensed drug, is injected into the salivary glands.
Non-pharmacological management involves encouraging good oral hygiene, using suction methods as necessary and ensuring appropriate hydration.
MND affects involuntary respiratory muscles, resulting in shortness of breath on exertion and poor cough reflex, leading to increased risk of respiratory tract infections and carbon dioxide retention. Patients will experience difficulty in lying flat, night-time waking, morning headaches and daytime fatigue.
Physiotherapists and respiratory medical teams advise on positioning and breathing exercises to regularly assess spirometry, appropriately manage sialorrhoea and treat respiratory tract infections that may arise, as respiratory failure with bronchopneumonia is a major cause of death in patients with MND.
Non-invasive intermittent positive pressure ventilation via a nasal mask may be used initially at night only to help control night-time symptoms. A ‘just in case’ kit, including an opioid and benzodiazepine can be offered, particularly when assisted ventilation is withdrawn.
Evidence demonstrates the benefit of morphine in the treatment of dyspnoea for patients with cancer, COPD and heart failure; however, there are no studies evaluating its use in patients with MND. Based on palliative care practice, data are extrapolated to conditions such as MND, whereby opioids have resulted in the reduction of patients’ sensation of breathlessness. In opioid-naive cancer patients, 1–2.5mg of morphine immediate release 4-hourly pro re nata (PRN) is used, titrated to response. For non-malignant conditions, smaller doses and less frequent administration may be adequate.
In MND, parenteral options must be considered if the patient is unable to swallow. In breathlessness associated with anxiety, 2–10mg diazepam daily with additional sublingual lorazepam PRN may be indicated. Likewise, the route of administration must be taken into account, with parenteral midazolam or levomepromazine being alternative options.
Invasive mechanical ventilation can prolong survival of patients with MND; however, there is no evidence showing improvement in QOL. It has high implications in terms of cost, carers and emotional strain and is, therefore, rarely used.
Effect on speech
SALTs can carry out a review of the patient’s speech and different forms of communication, while neuropsychologists can formally assess and support the patient as language capacity deteriorates. Communication aids, such as pen and paper, tablets and other speech-generating devices can perpetuate the patient’s ability to communicate for as long as possible. Dexterity will require continual assessment as patients become unable to write and need further technological input, such as computerised speech synthesisers.
Patients with MND may also experience:
Cognitive and behavioural changes;
Patients with anxiety and depression may benefit from interaction with support groups, online forums and counselling, as well as from pharmacological management as per guidelines for non-MND patients.
As the patient approaches the end of their life, the palliative care team must consider the proper timing to discuss this event with them and their family. The patient’s cognition and mental capacity should be taken into account and psychological support sought, if beneficial.
Riluzole is currently the only drug licensed for the treatment of individuals with ALS and has been shown to slow down the progression of the disease. It should be initiated by a neurological specialist with expertise in the management of MND.
Box 1 provides an example of how MND is managed by a MDT in Dorset, while Box 2 provides a patient perspective on the condition.
Further research is necessary to elucidate the cause of MND, to develop and improve current treatment strategies, and to slow disease progression. Current NICE guidance recommends further research into the ALS Prognostic Index and whether this is an accurate predictor of survival in people with MND, as well as how to manage sialorrhoea.
This Article First Published https://www.pharmaceutical-journal.com