Table 1:

Recommendations with level of evidence grade for the management of patients with amyotrophic lateral sclerosis*

Recommendations
Communication of diagnosis
  • The approach to communicating the diagnosis should be tailored to the patient’s individual needs (EC).

  • The diagnosis of ALS should be confirmed by a neurologist or physiatrist with training and expertise in ALS (EC). Patients referred for confirmation of an initial diagnosis of ALS should be seen in an ALS specialty clinic within 4 weeks (EC). Timely clinical contact by the specialty ALS clinic after confirmation of diagnosis is recommended (EC).

  • Discussion about ALS treatments and ALS research should occur. Patients should be provided with written information about ALS resources (paper- or Internet-based) and encouraged to register with their local and national ALS society (EC).

  • Discussions on prognosis are important and should be tailored to the individual but need not be discussed at initial diagnosis unless specifically requested (EC).

Disease-modifying therapies
  • Disease-modifying therapies should be prescribed by clinicians with experience in managing patients with ALS (EC).

  • Riluzole:

    • Riluzole has demonstrated efficacy in improving survival in ALS (level A).

    • There is evidence that riluzole prolongs survival by a median duration of 3 months (level A).

    • Riluzole should be started soon after the diagnosis of ALS (EC).

    • Regular monitoring of potential adverse effects of riluzole is important (EC).

    • There is insufficient evidence to suggest that riluzole loses clinical efficacy with progression of disease, including development of respiratory insufficiency (EC).

  • Edaravone:

    • In a select group of patients, intravenous edaravone has been shown to slow decline on the ALSFRS-R scores compared against intravenous placebo, over a 6-month period (level B). (These patients have shown benefit from edavarone: disease duration < 2 y, FVC > 80%, all ALSFRS-R subcomponents scores > 2, and demonstrated steady decline in the ALSFRS-R over a 3-mo interval.)

    • Evidence for benefit of intravenous edaravone at other stages of ALS has not been demonstrated (EC).

    • As with any other therapies, individualized goals, risks and benefits should be carefully considered and discussed before intravenous edaravone is initiated (EC).

  • Physicians are encouraged to have an open dialogue with their patients about the potential risks and benefits of unapproved therapies (EC).

Multidisciplinary care
  • Patients with ALS should be referred to specialized ALS multidisciplinary clinics for optimized health care delivery (level B).

  • Patients and health care authorities should be educated on the rationale for patient attendance at a multidisciplinary clinic. Benefits include:

    • Survival benefit (level B).

    • Fewer and shorter hospital admissions than patients not attending such clinics (level B).

    • Increased use of adaptive equipment (level C).

    • Increased use of riluzole, percutaneous feeding tubes and NIV (level B).

    • Enhanced QOL (level C).

  • Multidisciplinary care should be delivered through a team-based approach, with physicians and other health professionals addressing issues including communication, nutrition, swallowing, mobility, activities of daily living, respiratory care, cognition, psychosocial issues, medical management and end-of-life care (EC).

  • The frequency of multidisciplinary clinic visits will be dictated by the patient’s needs and rate of progression (EC).

  • A dedicated nurse or other clinic allied health care professional should be available to support patients and their family members for ALS issues between clinic visits (EC).

  • Telemedicine and telehealth monitoring are feasible and may be able to supplement clinic-based multidisciplinary care (level C).

Respiratory management
Screening
  • Patients with ALS need regular respiratory monitoring at baseline and every 3 months, or as clinically indicated (EC). Regular respiratory monitoring should include:

    • Symptom review, including dyspnea, orthopnea and morning headaches (level C).

    • Measurement of sitting FVC or slow vital capacity (level B).

    • One or more of the following: SNIP, supine FVC or MIP (level C).

    • Arterial blood gases, venous blood gas or transcutaneous CO2, when hypercapnia is suspected or when bulbar impairment precludes accurate testing (level C).

    • PCF measurement to assess cough effectiveness (level C).

    • Nocturnal oximetry or overnight polysomnography, when symptomatic sleep-disordered breathing is suspected and other daytime indications for NIV initiation are not present (level C).

Ventilation
  • NIV is the standard of care to treat respiratory insufficiency in ALS, both to lengthen survival and treat symptoms (level B).

  • Criteria for NIV initiation are any of the following:

    • Symptoms of respiratory insufficiency, including orthopnea (level B).

    • SNIP ≤ 40 cm H20 or MIP ≤ 40 cm H20 (level C).

    • Upright reliable FVC < 65% (EC).

    • FVC sitting or supine < 80% with symptoms or signs of respiratory insufficiency (level B).

    • Daytime hypercapnia pCO2 > 45 mm Hg (level B).

    • Abnormal nocturnal oximetry or symptomatic sleep-disordered breathing (level B).

  • A respiratory specialist should be consulted to initiate NIV (EC).

  • In any patient with the above indications, NIV should be initiated within 4 weeks. Severely symptomatic patients will need more urgent initiation. An overnight polysomnogram is not required for initiation of NIV (EC).

  • Ensure in-home NIV respiratory support for education, titration and troubleshooting (EC).

  • Patients should be informed that use of NIV may change the survival trajectory in ALS and the end-of-life experience (EC).

  • NIV enhances QOL in patients with ALS who have respiratory insufficiency (level B).

  • There should be ongoing assessments by a specialized respiratory therapist who can optimize modes, pressure and interfaces of NIV. Monitoring should include device download and may include nocturnal oximetry (level C).

  • Oxygen should not be considered a routine treatment for chronic respiratory insufficiency. In patients with ALS with acute hypoxemia, management of respiratory insufficiency with NIV needs to be considered first. If hypoxemia remains after optimal NIV pressure is applied, the etiology of the hypoxia needs to be assessed and supplemental oxygen can be considered (EC).

  • Diaphragm pacing should not be used in ALS because it is not effective and likely harmful in patients with ALS (level B).

  • NIV is the recommended treatment for ventilation even when ventilation is required 24 hours per day (EC).

  • Mouthpiece ventilation can be considered in carefully selected patients as a form of NIV during the day in addition to nocturnal NIV (EC).

  • In respiratory impairment that cannot be effectively managed by NIV, invasive ventilation is an option in carefully selected patients. Discussions pertaining to goals of care and advanced directives should occur well in advance of respiratory failure (EC).

  • Patients need to understand that ALS will continue to progress even with ventilatory support (EC).

  • Advanced care planning discussions should include explicit information about all respiratory interventions. Discussions should include the fact that intubation may be irreversible depending on the disease stage, and palliative options for breathlessness (please refer to the Palliative Care section). Discussions should also include the option of removing any treatment that has been initiated (EC).

  • Tracheostomy can be considered for upper airway obstruction with vocal cord paresis; however, discussions of long-term invasive ventilation should also occur (EC).

Airway clearance management
  • Lung volume recruitment strategies (level C) and manual assisted coughing (EC) should be initiated when patients report difficulty clearing airway secretions.

  • MIE twice daily should be considered for secretion clearance in patients with ALS who have reduced PCF (< 270 L/min). Increased MIE frequency should occur during an acute chest infection (EC).

  • Ensure in-home respiratory support of MIE for education, titration and troubleshooting (EC).

  • Pharmacotherapy with mucolytics (i.e., guaifenesin or N-acetylcysteine), a β-receptor antagonist (e.g., metoprolol or propranolol), nebulized saline or nebulized ipratropium can be considered (EC).

Nutritional management
Monitoring and enteral intervention
  • Nutritional status should be monitored by weight and BMI every 3 months, or as clinically indicated (level B); TDEE may be considered (level B).

  • Nutritional interventions, including dietary alteration and consideration of referral for enteral tube insertion, are indicated at diagnosis or at follow-up if there is: (1) increased risk of aspiration despite consistency modifications and compensatory recommendations (EC); (2) ≥ 5%–10% reduction in weight from usual or baseline weight (level C); (3) ≥ 1-point reduction in BMI from usual or baseline BMI (level B); (4) BMI < 18.5 (level B); or (5) TDEE exceeds daily energy intake (EC).

  • Information regarding potential benefits and risks of enteral feeding tubes should be provided early in the course of ALS management (EC).

  • A decrease in FVC approaching 50% should prompt consideration of referral for enteral tube insertion, even in the absence of dysphagia. An FVC < 50% should not necessarily preclude the recommendation of enteral feeding tube insertion as long as respiratory status is carefully monitored during and after the procedure (level C). NIV may improve safety of RIG or PEG insertion in patients with respiratory impairment (EC).

  • Regular monitoring of swallowing safety should be performed by a certified swallowing clinician (level B). Objective measures of swallowing impairment (modified barium swallow or FEES) can be used early and during the course of ALS management (EC).

Maximum allowable delay for PEG or RIG
  • Once a decision is made to insert an enteral feeding tube, insertion should be performed within 4 weeks. The ALS team should have access to endoscopists or radiologists who have interest and expertise in tube insertion (EC).

Feeding tube insertion
  • There is insufficient evidence to recommend PEG or RIG as the usual procedure for gastrostomy insertion (level C). There is weak evidence that RIG may be safer in patients with ventilatory impairment, as RIG does not require substantial sedation (EC).

  • Once a feeding tube is placed, an experienced clinician (endoscopist or radiologist) should be readily available to address immediate and late tube complications. There should be regular support by a registered dietitian with respect to the enteral feeds prescribed (EC).

  • Nasogastric tube feeding is not a preferred long-term option and should be reserved for those patients where no other procedure is possible and enteral nutrition is still desired (level C).

Diet modifications and nutrition support
  • High-calorie diets can be used to improve nutritional indicators (level B) and possibly survival (level C). High-calorie and high-carbohydrate diets may be better than high-calorie and high-fat diets (level B).

  • Parenteral nutrition is a potential source of nutrition in patients who cannot successfully have an enteral nutrition source; its use should be reserved for exceptional circumstances (EC).

Venous thromboembolism
  • There is likely an increased risk of VTE in patients with ALS. The risk appears heightened in ALS with leg onset and in patients with poor mobility (EC).

  • Clinicians are encouraged to consider VTE as a potential cause for new leg pain or new leg swelling in patients with ALS (EC).

  • There is no evidence to suggest screening for thromboembolism in asymptomatic patients with ALS (EC).

  • VTE prophylaxis has not been evaluated in patients in ALS and is not recommended in patients who have not been admitted to hospital (EC).

  • If VTE occurs in a patient with ALS, they should be anticoagulated as per standard VTE guidelines (EC).

Medication alignment
  • Primary care physicians and specialists should perform intermittent medication reviews and consider discontinuing any nonessential medications (EC).

  • Symptom management medications should be continued (EC).

  • Primary prevention medications should be discontinued if duration of effect is longer than the expected survival (EC).

  • Patients and health care professionals can be reassured that premorbid statin administration does not appear to contribute to the development of ALS (level B).

  • There is insufficient evidence to recommend discontinuation of statins in all patients with ALS. Discontinuation of statins may be considered based on the patient’s expected survival and their cardiovascular risk (EC).

Symptom management
Pain
  • Pain is a recognized consequence of ALS, with many potential causes (EC).

  • Patients must be queried regularly about pain symptoms. Pain should be regularly assessed and treatments should be tailored toward the specific cause (EC).

Fasciculations
  • In most patients, fasciculations do not need medication management (EC).

  • If fasciculations cause substantial distress, gabapentin can be considered (lev

Sialorrhea
  • Anticholinergic medications are the first-line therapy of sialorrhea. Individual medication choices should be tailored to patient factors (EC).

  • If one anticholinergic medication is ineffective, switching to another anticholinergic medication should be considered (EC).

  • Oral suction can be used as an adjunct therapy in managing sialorrhea (EC).

  • Botulinum toxin is effective for management of sialorrhea in ALS (level A). It can be used as second-line therapy and should be considered after feeding tube insertion because of the theoretical risk of worsening swallowing or airway integrity (EC).

  • Focal salivary gland radiation is an option for management of sialorrhea (level C) as second- or third-line therapy.

Pseudobulbar affect
  • Patients and families should be educated that pseudobulbar affect is a symptom of ALS and does not necessarily represent a symptom of depression or impaired cognition (EC).

  • Pseudobulbar affect does not require treatment unless it is distressing to the patient (EC).

  • If treatment is warranted, medications that may co-treat concomitant symptoms (e.g., amitriptyline for sleep and mood effect, SSRI for depression) may be considered (EC).

  • Dextromethorphan (20 mg) combined with quinidine (10 mg) can be used for treatment of pseudobulbar affect (level B).

Spasticity
  • Stretching can be useful for managing spasticity (level C).

  • If pharmacologic management of spasticity is required, baclofen, tizanidine, botulinum toxin, benzodiazepines and cannabinoids could be considered (EC).

  • There is insufficient evidence to recommend intrathecal baclofen for spasticity management in patients with ALS (EC).

Cramps
  • Muscle cramps need to be differentiated from other causes of pain (EC).

  • First-line management could include tonic water, gabapentin and baclofen (EC).

  • Second-line treatment could include quinine, levetiracetam and mexiletine (EC).

Depression
  • Depression should be treated in ALS, as it has a substantial impact on patient well-being (EC).

  • SSRIs or SNRIs can be used to treat depression in ALS (EC).

  • Nonpharmacologic supports could be considered, such as those offered through psychology, social work, psychiatry or spiritual care (EC).

Anxiety
  • Anxiety should be treated in ALS as it has a substantial impact on patient well-being (EC).

  • It is important to determine if anxiety is related to respiratory insufficiency and, if present, treat appropriately (EC).

  • If depression is concurrently present, an SSRI should be prescribed (EC).

  • Benzodiazepines can exacerbate respiratory insufficiency (EC).

  • Nonpharmacologic supports can be considered, such as those offered through psychology, social work, psychiatry or spiritual care (EC).

Insomnia
  • There are multiple causes of insomnia, such as respiratory insufficiency and depression, that should be appropriately investigated (EC).

  • Respiratory investigations and sleep studies could be considered to determine the type and cause of insomnia (EC).

  • Pharmacologic management of insomnia will depend on the cause (EC).

Fatigue
  • Reversible causes of fatigue should be considered, such as respiratory insufficiency, sleep disorders, depression, medication adverse effects and riluzole use (EC).

  • In patients developing fatigue while taking riluzole, reducing or discontinuing the drug may be considered (level C).

  • Having an occupational therapist discuss energy conservation techniques with patients may be considered (EC).

Dysarthria
  • Patients with dysarthria should be regularly followed by a speech language pathologist to ensure timely communication interventions (EC).

  • Use of augmentative and alternative communication devices should be offered to eligible patients in early disease stages (EC). Patients in later disease stages will also benefit from communication devices and strategies (EC).

  • The choice of communication devices should be tailored to the patient’s needs and abilities (EC). Patients with cognitive impairment may need individualized strategies for communication (EC).

  • Augmentative and alternative communication strategies may reduce caregiver stress (EC).

  • Voice amplification should be offered to patients with reduced vocal projection (EC).

  • Voice banking should be offered to appropriate patients (EC).

  • Providing access to different modes of communication, including social media, can allow independence, participation and better QOL (EC).

Exercise
  • In early ALS, regular moderate-intensity exercise is probably beneficial for function and QOL (level B). A personalized exercise program, including strength and aerobic training, should be suggested to patients who are able to participate (EC):

    • Submaximal effort for resistance should be encouraged.

    • Moderate-intensity physical activities are those that will cause adults to sweat a little and to breathe harder.

  • Moderate-intensity exercise is well tolerated and not harmful in ALS (level B):

    • Post-exercise fatigue or pain should resolve in 30 minutes and not interfere with daily activities; the exercise program should be adjusted otherwise.

  • A regular stretching and range-of-motion program is recommended for management of spasticity (level C), pain (EC) and prevention of contractures (EC).

    • Stretching and range-of-motion exercise can be done independently (active), with assistance (passive) or in combination (active-assist)

Cognition and behaviour
  • Screening for cognitive and behavioural impairment should be performed in patients with ALS early in their disease (level B).

  • If there is concern about cognition or behaviour at any point, specific assessments should take place with the person and their family members or caregiver, as appropriate (EC).

  • There are no studies on the use of pharmacologic agents to manage cognitive or behavioural impairment in ALS.

  • Because the presence of frontotemporal dementia negatively affects survival, ACP should be done early in the disease (EC).

  • The presence of cognitive or behavioural impairment should not necessarily preclude the recommendations for NIV or gastrostomy insertion. However, the challenges of intervention compliance with cognitive or behavioural impairment should be discussed with the patient and family before deciding to proceed with an intervention (EC).

  • A multidisciplinary approach can be considered to manage particularly problematic behaviours. Involving a behavioural specialist (such as an occupational therapist or psychologist) or psychiatrist for assistance may be considered (EC).

Caregivers
  • Health care providers should be attentive to the needs and emotional well-being of caregivers. Caregivers should be involved in planning for the impact of ALS on both the patient and themselves (EC).

  • Multidisciplinary clinics should be aware of the financial strain on caregivers and provide information on existing relief programs where possible (EC).

  • Assessment of caregiver burden, coping strategies, mood and family dynamics would assist in identifying caregivers and families in need of respite and supportive services. Local ALS societies may have resources for family members and caregivers (EC).

Palliative care
Timing
  • Palliative care of patients with ALS can be provided throughout the disease course by ALS clinic staff, palliative care practitioners and family physicians (EC).

  • Palliative care should be introduced if there is severe physical (i.e., pain, dysphagia or dyspnea), psychosocial or existential distress (EC).

  • To ensure integrated continuity of care, community palliative care services could be introduced before advanced-stage ALS (EC).

Treatments
  • Clinicians must clarify with their patient who is experiencing breathlessness whether the goal of care is prolonging life versus comfort-focused care for a good death (EC).

  • Clinicians should assess and relieve factors contributing to breathlessness, such as oral secretions and anxiety (EC).

  • Opioids can be titrated to relieve breathlessness (EC).

  • Air flow across the face to help with breathlessness may be considered (EC).

  • Conversations about ACP should be initiated early in the disease or whenever the patient inquires. Ongoing discussions about ACP and goals of care should be part of routine ALS follow-up (EC).

  • Patients should be encouraged to discuss their preferences about end-of-life care with family members and caregivers (EC).

  • Palliative care should be integrated into routine patient management before the terminal phase of ALS (EC).

  • Use of NIV and PEG tubes should be continued in palliative care for symptom relief and QOL, as dictated by patient preference (EC).

Withdrawal of ventilatory support
  • Withdrawal of continuous ventilatory support should be performed only after consultation and planning with a health care professional with expertise in ventilation withdrawal and palliative sedation (EC).

  • Adequate anticipatory symptom control with opioids and benzodiazepines should be achieved before withdrawal of ventilation occurs (EC).

  • Debriefing and psychosocial support for family and health care providers should be offered (EC).

Bereavement
  • Psychosocial support for bereaved caregivers should be provided. Early discussion about and support for the bereavement process could be initiated even before the patient’s death (EC).

Medical assistance in dying
  • Discussions about MAiD should be directed to a physician or nurse practitioner, abiding by regional guidelines (EC).

  • Physicians caring for patients with ALS are required to provide access to information about MAiD when requested (EC).

  • Clinicians should not assume that questions about MAiD constitute a request for MAiD. However, questions about MAiD should also open a discussion about end-of-life care and ACP (EC).

  • Patients pursuing MAiD should be provided concurrent palliative and supportive care (EC).

Organ donation
  • Patients with ALS may be accepted as solid organ donors, as determined by their local organ donation organization (EC).

  • Patients with ALS cannot donate tissue, such as corneas, skin or bone (EC).

  • Clinics should direct inquiries about donation to their provincial organ donation organization (EC).

  • Patients may be able to donate their tissues upon death for ALS research (EC).

  • Note: ACP = advanced care planning, ALS = amyotrophic lateral sclerosis, ALSFRS-R = Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised, BMI = body mass index, EC = expert consensus, FEES = fibreoptic endoscopic evaluation of swallowing, FVC = forced vital capacity, MAiD = medical assistance in dying, MIE = mechanical insufflation-exsufflation, MIP = maximal inspiratory pressure, NIV = noninvasive ventilation, PCF = peak cough flow, pCO2 = partial pressure of carbon dioxide, PEG = percutaneous endoscopy gastrostomy, QOL = quality of life, RIG = radiologically inserted gastrostomy, SNIP = sniff nasal inspiratory pressure, SNRI = serotonin–norepinephrine reuptake inhibitors, SSRI = selective serotonin reuptake inhibitor, TDEE = total daily energy expenditure, VTE = venous thromboembolism.

  • * See Box 2 for criteria for levels of evidence supporting the recommendations.

  • If pulmonary testing is not reliable (i.e., in patients with bulbar impairment or with severe cognitive impairment), clinicians must rely on symptoms or other measures for respiratory screening.

  • The patient’s home can be a house, apartment, long-term care facility or hospice.