amyotrophic%20lateral%20sclerosis
AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with undetermined etiology that primarily involves the motor neurons in the cerebral cortex, brainstem and spinal cord.
There is no cure and the mean duration of survival is 2-5 years without tracheostomy and ventilator support.
Clinical hallmarks of ALS are: presence of upper & lower motor neuron features involving the brainstem and spinal cord and progressive limb weakness, respiratory insufficiency, spasticity, hyperreflexia, and bulbar symptoms such as dysarthria and dysphagia.

Pharmacotherapy

Disease-Modifying Agent

Riluzole

  • Neuroprotective drug for patients with amyotrophic lateral sclerosis (ALS)
  • Daily dose of 100 mg Riluzole have seen to have improved the 1-year survival by 15% and prolonged survival by approximately 3 months after 18 months treatment
  • Glutamate antagonist
    • Inhibits presynaptic glutamate release and interferes with its postsynaptic effects
  • Not a cure for ALS, but produces modest lengthening of survival
    • May increase survival by 3-6 months
    • Efficacy has not been demonstrated in late phase of disease
  • Increased survival rates have been shown after 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
    • Forced vital capacity (FVC) > 60% predicted
    • No tracheostomy
Edaravone
  • Potent free radical scavenger and antioxidant that can give neuroprotection against oxidative stress
  • Approved in Japan, Korea and recently in the United States for treatment of amyotrophic lateral sclerosis
  • Not for a cure but studies shows it may slow the decline of functional abilities in some patients with amyotrophic lateral sclerosis
  • Can be an adjunct to Riluzole in early stage of amyotrophic lateral sclerosis

Symptomatic Management

  • Goal of symptom management is to improve quality of life for both the patient and family

Sialorrhea

  • Glycopyrrolate, Benztropine, Hyoscine, Trihexyphenidyl, Atropine
    • Have been used to control sialorrhea in patients with other diseases where sialorrhea is a problem (eg cerebral palsy, developmentally disabled)
  • Amitriptyline
    • Has been used widely in amyotrophic lateral sclerosis patients to control sialorrhea
    • May be used to treat combination of symptoms (eg depression, sialorrhea, pseudobulbar affect, nocturnal sedation and possible weight gain)
    • Side effects may limit usefulness
  • Botulinum toxin type B injection into salivary glands should be considered in amyotrophic lateral sclerosis patients with refractory sialorrhea

Bronchial Secretions

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

Dyspnea

  • Morphine, given subcutaneously, may provide relief in amyotrophic lateral sclerosis patients with dyspnea at rest
  • Benzodiazepines (eg Midazolam, Diazepam, Lorazepam) may also be used

Pseudobulbar Affect

  • Amitriptyline
    • Randomized controlled trial in multiple sclerosis (MS) patients supported its use
    • May be beneficial in patients with drooling
  • Fluvoxamine
    • Satisfactory results were reported in a single study that included amyotrophic lateral sclerosis patients
  • Citalopram
    • Has been tested with good effects in other neurologic diseases
  • 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
    • May cause weakness, sedation and dizziness
  • Levetiracetam may be tried for cramps
    • If unsuccessful or side effects occur, Quinine sulfate (200 mg twice daily) may be of benefit
  • Antispasctic drugs such as Baclofen and Tizanidine may be tried
    • If spasticity is severe despite oral medications, intrathecal Baclofen may be helpful

Pain

  • Non-opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) may be initial treatment options
  • If non-opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) fail, may switch to opioid analgesics

Depression

  • Treat with appropriate antidepressant eg Amitriptyline, a selective serotonin re-uptake inhibitor (SSRIs), or Mirtazapine
  • Selective serotonin re-uptake inhibitor (SSRIs)  are preferred in elderly or cognitively impaired patients
  • Anxiety can be treated with Bupropion or benzodiazepines eg Diazepam,or Lorazepam

Insomnia and Fatigue

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

Venous Thrombosis

  • Should be treated with anticoagulants

Non-Pharmacological Therapy

Nutritional Management

  • Patients with dysphagia are at risk for dehydration and nutritional deficiencies
    • Symptoms of dysphagia: Drooling, choking on fluid/food, jaw weakness, slow eating
    • Speech pathologists may be helpful in assisting patients who have swallowing problems
    • Safe swallowing techniques and modified diet are highly recommended
  • The timing of percutaneous endoscopic gastrostomy (PEG)/percutaneous radiological gastrostomy (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 supplemental or alternative nutritional route as dysphagia progresses
    • Ensures sufficient caloric and fluid intake
  • It is recommended that PEG be placed prior to forced vital capacity (FVC) falling <50% of predicted
    • Should be offered to patients with substantial weight loss, even in the absence of dysphagia
  • Advantages: Adequate nutrition intake, weight stabilization and route for medication

Respiratory Management

  • Resp failure indicates combined degeneration of central respiratory centers and motor neurons contributing to the phrenic nerve
  • Resp insufficiency must be continuously monitored and serial pulmonary function measurements are recommended
  • Symptoms of respiratory insufficiency includes 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 auxillary respiratory muscles, paradoxical movement of the abdomen, decreased chest wall movement, weak cough, sweating, tachycardia, morning confusion, hallucinations, weight loss, mouth dryness
  • If forced vital capacity (FVC) falls <50% even in absence of symptoms, planning for invasive or noninvasive ventilation needs to be discussed with patient/family
    • Patient’s wish regarding termination of ventilation needs to be discussed
  • Noninvasive ventilation is usually preferred over invasive ventilation with tracheostomy
    • Noninvasive ventilation offers clinical benefit to patient by improving symptoms of hypoventilation and therefore quality of life
    • Invasive ventilation may be more effective in increasing survival, but is more expensive and requires more patient care

Communication

  • Speaking rate of amyotrophic lateral sclerosis (ALS) patients is a good indicator of overall bulbar deterioration
  • Dysarthria leads to communication difficulties
    • Should be regularly assessed and managed by a speech therapist
    • Use appropriate communication support systems from pointing boards with figures or words to computerized speech synthesizers
  • Family and caregivers should be educated
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