Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) — also called motor neuron disease — is a progressive neurodegenerative disease that destroys both upper motor neurons (in the motor cortex and corticospinal tracts) and lower motor neurons (in the brainstem and spinal cord), producing a combination of spasticity, hyperreflexia, and pseudobulbar features alongside muscle weakness, wasting, fasciculations, and hyporeflexia — often in the same body region.^[1] No currently available therapy in Canada reverses or halts the underlying neurodegeneration. Care combines disease-modifying pharmacotherapy that has a modest effect on the pace of decline with comprehensive multidisciplinary symptomatic, respiratory, and nutritional support, together with early and ongoing goals-of-care planning — ALS is ultimately a terminal illness, and most patients die of respiratory failure.^[2] The single most consistent finding across Canadian and international guidance is that regular follow-up in a multidisciplinary ALS clinic — not any one drug — is the intervention most closely linked to better outcomes.^[1]

The diagnostic hallmark of ALS is the combination of UMN and LMN signs together, in the same body region and progressively spreading to other regions — a pattern not explained by a single focal lesion, and different from a disease that stays purely UMN- or purely LMN-limited.

Onset patterns

• Limb onset (most common): asymmetric distal weakness — a foot drop, or hand clumsiness affecting fine motor tasks such as buttoning or writing — that progressively spreads to other limbs and regions.
• Bulbar onset: dysarthria (slurred or slowed speech) and/or dysphagia as the presenting symptoms.
• Respiratory onset (uncommon): dyspnea or orthopnea as the presenting symptom, with minimal limb involvement initially — easily missed or misattributed to a primary respiratory or cardiac cause at first presentation.

Cognitive and behavioural change occurs along a spectrum in ALS, from isolated executive dysfunction to frank frontotemporal dementia (ALS-FTD). Screen for this specifically — it affects decision-making capacity, medication adherence, and the timing of advance-care-planning conversations, so it should not be assumed absent just because a patient's language is fluent and their limb weakness is the dominant visible problem.

• Increasing age, with peak onset generally in the 6th and 7th decades of life.
• Male sex — a modest male predominance is consistently reported, particularly for limb-onset disease.
• Family history of ALS or frontotemporal dementia, or a known pathogenic gene variant — most familial ALS is linked to a C9orf72 hexanucleotide repeat expansion, with SOD1, FUS, and TARDBP among the other recognized causative genes.
• Military service — an association between military service and ALS risk is consistently reported across studies, though the underlying mechanism is not established.
• Cigarette smoking.
• No reliably modifiable environmental risk factor has been established for sporadic ALS; proposed associations with specific occupational or toxin exposures remain inconsistent across studies and should not be presented to patients as an established cause.

Distinguishing ALS from its key mimics

Diagnostic approach

ALS remains a clinical diagnosis, supported by electrophysiologic and imaging findings that establish the extent of lower motor neuron involvement and exclude alternative explanations. The revised El Escorial/Awaji framework is the tool most commonly used to categorize diagnostic certainty (definite, probable, or possible ALS) based on how many body regions — bulbar, cervical, thoracic, and lumbosacral — show combined UMN/LMN involvement.^[1]

Investigations

• Electromyography (EMG) and nerve conduction studies — to confirm widespread lower motor neuron involvement (active and chronic denervation) across multiple regions, and to exclude multifocal motor neuropathy and other neuropathic or myopathic mimics.
• MRI of the brain and spinal cord — primarily to exclude structural mimics, especially cervical spondylotic myelopathy.
• Baseline bloodwork: creatine kinase (mild-to-moderate elevation is common in ALS itself and should not be mistaken for a primary myopathy), TSH, vitamin B12, HIV serology, and serum protein electrophoresis.
• Anti-GM1 ganglioside antibodies when multifocal motor neuropathy is a genuine clinical consideration.
• Genetic counselling and testing (e.g., C9orf72, SOD1, FUS, TARDBP) for a patient with a family history of ALS or frontotemporal dementia, or notably young age at onset — arrange pre- and post-test genetic counselling given the implications for the patient's relatives.

Functional status is tracked longitudinally with the Revised ALS Functional Rating Scale (ALSFRS-R), a 12-item questionnaire scored out of 48 and repeated at every multidisciplinary visit — the standard tool for tracking disease trajectory in both practice and clinical trials. It is not reproduced here as an interactive calculator: correct scoring depends on the full standardized item wording and clinician judgment on each item, not an independently verifiable point-sum a pharmacist could safely reimplement.

• Slow the rate of functional decline using disease-modifying pharmacotherapy, understanding that no currently available therapy in Canada halts or reverses disease progression.
• Achieve and maintain the best possible control of every individual symptom domain — spasticity, sialorrhea, pseudobulbar affect, pain, mood, sleep, and cramps — since these accumulate and interact as the disease progresses.
• Anticipate and proactively manage respiratory decline, rather than reacting only once respiratory failure is already symptomatic.
• Maintain nutritional status and safe swallowing for as long as possible, escalating to enteral feeding before a nutritional or respiratory crisis forces the decision.
• Preserve the patient's ability to communicate for as long as possible, introducing augmentative and alternative communication tools before speech is severely impaired.
• Support the patient and family through a multidisciplinary ALS clinic model, with palliative care integrated early rather than reserved for the end of life.
• Elicit and regularly revisit the patient's goals of care — regarding ventilatory support, enteral feeding, and end-of-life preferences — while the patient still retains full decision-making capacity and communication ability.

The multidisciplinary ALS clinic model

Care coordinated through a dedicated multidisciplinary ALS clinic — bringing neurology, respirology, physiatry/physiotherapy/occupational therapy, speech-language pathology, dietitian, social work, and palliative care together, ideally within the same visit — is the central organizing recommendation of current Canadian guidance, and pharmacists are an integral part of this team for medication review, symptom-management optimization, drug-access navigation, and adherence support.^[1]

• Physiotherapy and occupational therapy: maintain range of motion, prevent contractures, provide mobility aids and adaptive equipment, and complete a home safety assessment before falls or injuries occur.
• Speech-language pathology: introduce augmentative and alternative communication (AAC) strategies and devices proactively, while speech is still functional — waiting until speech is severely impaired makes learning new communication technology much harder.
• Respiratory therapy: teach airway clearance techniques, and introduce a mechanical insufflation-exsufflation ("cough assist") device once cough becomes weak or ineffective, to reduce aspiration and pneumonia risk.^[3]
• Dietitian: recommend texture-modified diets and calorie-dense oral supplementation as dysphagia progresses, and support the nutrition-related decision points below.
• Social work and palliative care: integrate palliative care early in the disease course as a partner in symptom management and advance-care planning, not only once the patient is imminently dying — this is an explicit recommendation of current Canadian guidance.^[1]
• Caregiver support: assess caregiver burden at every visit and connect families to respite and support resources; ALS places a substantial and progressively increasing caregiving demand on family members.

Respiratory support

Non-invasive ventilation (NIV) is the respiratory intervention with the clearest benefit in ALS and should be discussed proactively as respiratory function declines, rather than only once a patient is symptomatic in a respiratory crisis (see Clinical Decision Algorithm).^[3] Invasive ventilation (tracheostomy) is an option some patients choose for longer-term survival, but this decision — like NIV — should be discussed well in advance as part of ongoing goals-of-care conversations, not decided under emergency conditions.

Nutrition support

Percutaneous endoscopic gastrostomy (PEG) placement should be discussed proactively once dysphagia or weight loss develops, while pulmonary reserve is still adequate to tolerate the procedure safely (see Clinical Decision Algorithm) — deferring the conversation until oral intake has already failed closes the safest window for the procedure.^[2]

Hepatic impairment: riluzole undergoes substantial hepatic metabolism — avoid starting it in a patient with baseline transaminases already significantly elevated, and use tizanidine cautiously given its own hepatotoxicity signal.

Renal impairment: the edaravone oral suspension contains sodium benzoate, which can accumulate in significant renal or hepatic impairment — use caution and involve the prescriber before starting in this situation. Reduce gabapentin dosing for reduced renal function.

Cognitive impairment / ALS-FTD overlap: a patient with significant cognitive or behavioural involvement may lose the capacity to participate in complex treatment or advance-care-planning decisions as the disease progresses — complete these conversations, and confirm a substitute decision-maker, as early as possible rather than waiting until capacity is already in question.

Bulbar-predominant disease / dysphagia: confirm a patient can safely and reliably swallow oral tablets before relying on an oral regimen for a symptom that itself needs urgent control (e.g., significant sialorrhea or pain) — discuss alternative formulations or routes with the prescriber and pharmacy as dysphagia progresses, and revisit every regimen once a feeding tube is placed.

Older adults: use particular caution with any sedating symptomatic drug (opioids, gabapentin, tricyclic antidepressants, benzodiazepines) given the combination of reduced respiratory reserve and age-related pharmacokinetic change — start low and titrate slowly.

Riluzole-specific monitoring

• Baseline ALT, AST, bilirubin, and CBC before starting.
• Repeat transaminases monthly for the first 3 months of treatment, then periodically thereafter for the duration of therapy.
• Discontinue riluzole if ALT/AST rises above 5 times the upper limit of normal, if bilirubin rises, or if there are other signs of clinically significant liver injury.
• Assess promptly for neutropenia if fever develops, particularly within the first 2 months of treatment.
• Ask about new dry cough or breathlessness at every visit — a possible sign of riluzole-associated interstitial lung disease.

Respiratory monitoring

Perform a symptom review and spirometry (FVC or SVC) at every multidisciplinary visit. FVC alone is not a sufficient basis for NIV timing decisions — pair it with a structured symptom review (orthopnea, morning headache, daytime somnolence) and, where available, additional measures such as maximal inspiratory pressure, sniff nasal inspiratory pressure, or overnight oximetry.^[3]

Functional and nutritional monitoring

• Track the ALSFRS-R score at every multidisciplinary visit to follow the trajectory of decline.
• Track weight and swallowing function at every visit; involve the dietitian and speech-language pathologist proactively rather than only once a problem is already advanced.
• Reassess communication needs and augmentative/alternative communication device requirements regularly as speech changes.
• Screen for depression, anxiety, suicidal ideation, and caregiver burden at routine intervals — these are common, often underrecognized, and undertreated in ALS.^[7]
• Reassess goals of care regularly, not as a single conversation held only at diagnosis — preferences can and do evolve as the disease progresses.

1. Recognize that continued functional decline on riluzole and/or edaravone is expected — these drugs slow, not stop, disease progression. A falling ALSFRS-R score is not, by itself, evidence that the drug has "failed" or should be stopped.
2. Confirm adherence and rule out a correctable cause of accelerated decline (an intercurrent illness, a new medication interaction, or a new but treatable symptom driving apparent functional loss) before attributing everything to underlying disease progression.
3. Reassess respiratory status, nutritional status, and communication needs at every visit as clinical thresholds are crossed (see Clinical Decision Algorithm) — proactively raise NIV, PEG, or AAC rather than waiting for the patient or family to bring it up.
4. Escalate symptomatic therapy stepwise as new symptoms emerge or existing ones become refractory (for example, adding botulinum toxin for sialorrhea unresponsive to oral anticholinergics, or referring for intrathecal baclofen for refractory spasticity) — see Pharmacologic Treatment Options and Drug Tables.
5. Discuss eligibility for ALS clinical trials with the patient's neurologist if the patient is interested — trial availability changes over time, and referral to a comprehensive ALS clinic is the most reliable way to keep this option open.
6. Revisit goals of care explicitly whenever a major functional threshold is crossed — loss of independent ambulation, onset of respiratory insufficiency, or the need for a feeding tube — treating these as natural checkpoints for the conversation, not just the initial diagnosis visit.

• Withholding riluzole because its effect is "only modest" — a modest benefit is still a real benefit, and it should be offered to essentially every patient with confirmed ALS.
• Missing the scheduled liver enzyme monitoring after starting riluzole, particularly in the first 3 months.
• Prescribing a sedative-hypnotic (benzodiazepines, diphenhydramine) or an opioid for a non-pain, non-dyspnea indication without accounting for reduced respiratory reserve in a patient with ALS.
• Waiting for a patient to become symptomatic in a respiratory crisis before discussing NIV, instead of raising it proactively as clinical thresholds are crossed.
• Deferring the PEG discussion until a patient has already lost significant weight or pulmonary reserve, closing the safest window for the procedure.
• Misattributing pseudobulbar affect to depression, or vice versa — the two can coexist but need different confirmation and treatment approaches; screen specifically for the involuntary, mood-incongruent quality of pseudobulbar episodes.
• Over-drying secretions with an anticholinergic sialorrhea treatment to the point that thickened secretions become harder to clear and raise aspiration risk — titrate to the lowest dose that controls symptoms.
• Assuming the dextromethorphan-quinidine combination product used for pseudobulbar affect elsewhere is available in Canada — it is not currently marketed here; use an alternative such as amitriptyline.
• Delaying advance-care-planning and goals-of-care conversations until a patient has already lost the capacity or physical ability to communicate their wishes.
• Treating each new symptom in isolation rather than through the multidisciplinary ALS clinic, which is the setting most consistently linked to better outcomes.

How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Disease-modifying therapy

Offer riluzole to essentially every patient with confirmed ALS; discuss edaravone as an additional option, particularly in early-stage disease with preserved respiratory function.

Spasticity

Sialorrhea (excess salivation)

Step therapy: start with a first-line oral anticholinergic; move to botulinum toxin for severe, refractory symptoms.

Pseudobulbar affect and mood

The dextromethorphan-quinidine combination product used for pseudobulbar affect in some other countries is not currently marketed in Canada; antidepressants are the practical Canadian option.

Pain and cramps

Sleep and appetite

Evidence note: Drug inventory, dosing, adverse effects, interactions, and comments reflect standard Canadian practice, cross-checked against the Canadian best practice recommendations for ALS management and current AAN practice parameters.^[1][2]