Amyotrophic Lateral Sclerosis Management

Disease-Modifying Agent  

Riluzole  

Riluzole is a neuroprotective drug for patients with ALS. A daily dose of 100 mg of Riluzole has been seen to have improved the 1-year survival rate by 15% and prolonged survival by approximately 3 months after 18 months of treatment. It is a glutamate antagonist that inhibits the presynaptic glutamate release and interferes with its postsynaptic effects. It is not a cure for ALS but produces modest lengthening of survival. It may increase survival by 3 to 6 months. However, its efficacy has not been demonstrated in the late phase of the disease.  

Increased survival rates have been shown after the administration of Riluzole in patients with the following clinical features:

• Definite or probable ALS by World Federation of Neurology criteria
• Symptoms present for less than 5 years
• FVC >60% predicted
• No tracheostomy

Edaravone  

Edaravone is a potent free radical scavenger and antioxidant that can give neuroprotection against oxidative stress. It is approved in Japan, Korea, and recently in the United States for treatment of ALS. It is not a cure, but studies show it may slow the decline of functional abilities in some patients with ALS. It can be an adjunct to Riluzole in the early stage of ALS. 

Symptomatic Management  

The goal of symptom management is to improve the quality of life for both the patient and the family.  

Sialorrhea  

Drugs that can be used for sialorrhea include Glycopyrrolate, Benztropine, Hyoscine, Trihexyphenidyl, and Atropine. These drugs have been used widely in ALS patients to control sialorrhea in patients with other diseases where sialorrhea is a problem (eg cerebral palsy, developmentally disabled). Amitriptyline has been used widely in ALS patients to control sialorrhea. It may be used to treat a combination of symptoms (eg depression, sialorrhea, pseudobulbar affect, nocturnal sedation and possible weight gain). Its side effects may limit usefulness. Botulinum toxin type B injection into salivary glands should be considered in ALS patients with refractory sialorrhea. 

Bronchial Secretions  

Mucolytics like Guaifenesin and Acetylcysteine may be beneficial for thick mucus secretions. If the above measures are ineffective, nebulization with beta-agonists and/or anticholinergics bronchodilator and/or a mucolytic and/or Furosemide may be used in combination. It should only be used if there is sufficient cough flow.  

Dyspnea  

Morphine, given subcutaneously, may provide relief in ALS patients with dyspnea at rest. Benzodiazepines (eg Midazolam, Diazepam, Lorazepam) may also be used.  

Pseudobulbar Affect  

Randomized controlled trial in multiple sclerosis (MS) patients supported the use of Amitriptyline in those with pseudobulbar affect. It may also be beneficial in patients with drooling. Satisfactory results were reported in a single study that included ALS patients who used Fluvoxamine. Citalopram has been tested with good effects in other neurologic diseases. While Dextrometorphan with Quinidine have been shown to be effective in a Class IA study but tests on long-term side effects and tolerability are still lacking.

Cramps and Spasticity  

Baclofen, Tizanidine, Memantine, Diazepam, Dantrolene, Eperisone, or Tolperisone may be given in ALS patients with cramps and spasticity. However, they may cause weakness, sedation, and dizziness. Levetiracetam may be tried for cramps. If Levetiracetam is unsuccessful or if side effects occur, Quinine sulfate (200 mg twice daily) may be of benefit. Antispastic drugs such as Baclofen and Tizanadine may be tried as well. If spasticity is severe despite oral medications, intrathecal Baclofen may be helpful.  

Pain  

Non-opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) may be the initial treatment options for ALS patients with pain. If non-opioid analgesics and NSAIDs fail, one may switch to opioid analgesics.  

Depression  

Depression in ALS is treated with an appropriate antidepressant such as Amitriptyline, a selective serotonin reuptake inhibitor, or Mirtazapine. It must be noted that selective serotonin reuptake inhibitors (SSRIs) are preferred in the elderly or in cognitively impaired patients. Anxiety can be treated with Bupropion or benzodiazepines (eg Diazepam, Lorazepam).  

Insomnia and Fatigue  

Amitriptyline, Mirtazapine or appropriate hypnotics (eg Zolpidem) may be given to treat insomnia. Modafinil may be considered for debilitating fatigue.  

Venous Thrombosis  

Venous thrombosis should be treated with anticoagulants.

Patient and Family Education  

Delivery of Diagnostic News  

It is important to ensure that the diagnosis is given in person in a quiet, comfortable, and private location. The patient’s support network should be present. The patient’s knowledge of amyotrophic lateral sclerosis is determined. It is important that questions are allowed, and that reassurance is given. Just as important, the cultural and social background of the patient is respected. Written information about the disease and support groups are provided, if available. A second opinion is offered if the patient wants it. 

Reassurance  

It is important to explain that the complications of the disease are manageable. The patient is involved in the care decisions, and they are reassured that their treatment decisions will be respected.  

Sharing of Information  

Information needs to be provided to the patient and family in a timely manner which is appropriate for decision making. Needs are delivered well in advance of major management decision (eg mechanical ventilation).  

Genetic Counseling and Testing  

Genetic counseling and testing should only be offered in cases with a known familial history of ALS. Testing should be done voluntarily and with informed consent.

Nutritional Management  

Patients with dysphagia are at risk for dehydration and nutritional deficiencies. Associated symptoms of dysphagia include drooling, choking on fluid or food, jaw weakness, and slow eating. Speech pathologists may be helpful in assisting patients who have swallowing problems. Safe swallowing techniques and a modified diet are highly recommended. The timing of percutaneous endoscopic gastrostomy (PEG)/PRG is based on an individual approach taking into account bulbar symptoms, malnutrition (weight loss >10%), respiratory function, and the patient's general condition. Early insertion of a feeding tube is recommended.

Percutaneous Endoscopic Gastrostomy (PEG)  

PEG should be considered as a supplemental or alternative nutritional route as dysphagia progresses. This ensures sufficient caloric and fluid intake. It is recommended that PEG be placed prior to forced vital capacity (FVC) falling <50% of the predicted. It should be offered to patients with substantial weight loss, even in the absence of dysphagia. The advantages of PEG include adequate nutrition intake, stabilization, and route of medication.

Respiratory Management  

Respiratory failure indicates combined degeneration of the central respiratory centers and motor neurons contributing to the phrenic nerve. Respiratory insufficiency must be monitored, and serial pulmonary function measurements are recommended. Symptoms of respiratory insufficiency include dyspnea on minor exertion or talking, orthopnea, frequent nocturnal awakenings, excessive daytime sleepiness, daytime fatigue, morning headache, difficulty clearing secretions, apathy, poor appetite, poor concentration and/or memory.  

Signs of respiratory insufficiency are tachypnea, use of axillary respiratory muscles, paradoxical movement of the abdomen, decreased chest wall movement, weak cough, sweating, tachycardia, morning confusion, hallucinations, weight loss, and mouth dryness. If the FVC falls to <50% even in the absence of symptoms, planning for invasive or noninvasive ventilation needs to be discussed with the patient and family. The patient’s wish regarding the termination of ventilation needs to be discussed. Non-invasive ventilation is usually preferred over invasive ventilation with tracheostomy. Non-invasive ventilation offers clinical benefit to patients by improving symptoms of hypoventilation, and therefore the quality of life. Invasive ventilation may be more effective in increasing survival but is more expensive and requires more patient care.  

Communication  

The speaking rate of amyotrophic lateral sclerosis patients is a good indicator of overall bulbar deterioration. Dysarthria leads to communication difficulties. This should be regularly assessed and managed by a speech therapist. Appropriate communication supports systems are used from pointing boards with figures or words to computerized speech synthesizers. Family and caregivers should be educated.

Symptomatic Management  

Sialorrhea  

Sialorrhea or drooling may cause social stress and is associated with aspiration pneumonia. It tends to be due to poor handling of saliva. Suctioning secretions using a portable home suction device is recommended. It is also important to distinguish between thick mucus production and sialorrhea. Low-dose radiation therapy for medically refractory sialorrhea reduces salivary production, but may cause side effects (eg erythema, sore throat, nausea)  

Bronchial Secretions  

For bronchial secretions, a portable suction device and humidifier are provided. The patient and caregiver should be taught the technique of assisting expiratory movements using a manual-assisted cough. A mechanical cough-assisting device (insufflator-exsufflator) may also be used for acute respiratory infection. Cricopharyngeal myotomy may be done for frequent cricopharyngeal spasms and severe bronchial secretions.

Cramps and Spasticity  

Physical therapy, exercise, and hydrotherapy may help reduce cramps and spasticity.  

Pain (Musculoskeletal Pain, Skin Pressure Pain caused by Immobility)  

Pain in amyotrophic lateral sclerosis can be addressed by physiotherapy, repositioning and pressure area care, and pressure-relieving cushions and mattresses can be used.  

Venous Thrombosis  

Venous thrombosis may be prevented by physiotherapy, limb evaluation, and compression stockings.  

Weakness and Disability  

Physiotherapy and physical therapy may be used all throughout the course of the disease. Exercise may increase muscle strength, endurance, and range of motion. Orthotics (eg ankle foot orthosis, neck collars) and adaptive aids (eg walking frame, wheelchair) can also be used.  

Cognitive Decline  

In all patients with frontal dysexecutive syndromes, care needs to be taken to ensure informed consent during decision-making; capacity issues may need to be considered. Carers and healthcare professionals should be informed of the symptoms of dysexecutive syndrome and trained in their management. 

Palliative Care  

Shared decision-making between the physician and the patient is needed. Religious and cultural values need to be considered. Continued discussion throughout illness is important to understand and to follow the patient’s choices even if they change throughout their care. The goal is to provide adequate relief from symptoms at the terminal stage. Treating dyspnea, anxiety, and pain are also required. If available, hospice care is considered.