Palliative care in motor neuron disease
Gary Hsin, M.D.
November 18th, 2005
Using ALS as a model for discussion
Amyotrophic Lateral Sclerosis
Progressive, degenerative neurologic disease of unknown etiology
Involves both upper and lower motor neurons– LMN: weakness, atrophy, fasiculation due
to denervation of muscles – amyotrophic– UMN: hyperreflexia, spasticity due to
lateral corticospinal tract degeneration – lateral sclerosis
ALS continued Muscle atrophy and spasticity in limb
and bulbar muscles result in weakness and loss of ambulation, oropharyngeal dysfunction, weight loss, and ultimately respiratory failure.
The mainstay of treatment for ALS patients is still palliative and symptomatic management.
It is important to provide anticipatory guidance, and continue the discussion of goals of care.
Pathology & Etiology
Motor neuron degeneration and death Superoxide dismutase type 1 mediated
toxicity Excitotoxicity via glutamate mediated
signaling Cytoskeletal derangements,
mitochondrial dysfunction, viral infections, apoptosis
Epidemiology & Prognosis 5000 new case in the U.S. per year 90% cases sporadic, 10% familial Incidence 1.47~2.7 per 100,000 per year Prevalence 2.7~7.4 per 100,000 per year 70% die within 3~5 years of diagnosis 10~20% survive for more than 10 years Improved survival associated with younger
age of onset, male gender and limb rather than bulbar symptoms
Riluzole
Riluzole reduces the presynaptic release of glutamate, but the precise mechanism of action in ALS is unclear. It is postulated that it may be neuroprotective by reducing excitotoxicity that is due to excess glutamate, and it may also act as a glutamate receptor antagonist.
Riluzole continued
Clinical trials so far do show that Riluzole improved survival, especially in younger populations, but demonstrated no beneficial effect on bulbar function or muscle strength
The pts who are most likely to benefit are those who have symptoms for less than 5 years, vital capacity >60%, and no tracheostomy. 50mg PO BID.
Signs & Symptoms Limb spasticity Hyperreflexia Brisk jaw reflex Babinski's sign Pseudobulbar palsy with emotional lability Focal or multifocal limb weakness & atrophy Cramps & fasciculations Dysarthria, dysphagia and/or choking Tongue atrophy with fasciculations Claw hand Fatigue Dyspnea
Secretion management
In ALS there is overall decreased saliva production, sialorrhea is more a poor handling of saliva.
The management is similar for pts with cerebral palsy, MR, oropharyngeal carcinoma, Down syndrome.
Decrease saliva production, or divert and remove saliva
Secretion management Glycopyrrolate (Robinul) 1~2mg BID or
TID Benztropine (Cogentin) 0.5~2.0mg QD
or BID or Atropine 0.4mg Q4~6 hours Amitriptyline (Elavil) 10~150mg QHS Transdermal scopolamine one or two
patches every three days Trihexyphenidyl (Artane) 1 to 2 mg per
day slowly increasing to total of 5 to 15 mg daily in three or four divided doses
May also try Clonidine, Levsin
Secretion management
Botulinum toxin injection into the salivary glands appears to be safe and useful in preliminary studies
External beam radiation [3-30 Gy; 3-10 fractions]
Surgical interventions have been tried w/o demonstrated efficacy
Secretion management
Thick secretions/mucus– Increase fluid intake– Humidified air– Propranolol or Metoprolol
Secretion management
Non-pharmacologic management– Suction machine (not usually helpful for
thick mucus, but helpful with sialorrhea)– Mechanical insufflation-exsufflation (In-
Exsufflator cough machine)– Manually assisted coughing techniques
Secretion managementAAN practice parameters
Muscle spasm & weakness
Early PT/OT involvement Variety of assist devices may provide,
mobility, support, comfort and increase functionality, i.e. braces, wheelchair, special air beds, head rests, etc.
Muscle spasm & weakness
Cramps– Quinine sulfate 200 mg twice a day– Tizanidine 2 to 4 mg by mouth twice daily
up to a total dose of 24 mg daily– Carbamazepine 200 mg twice daily– Phenytoin 100 mg once to three times a day– For mild symptoms:
• Magnesium 5 mmol once to three times a day• Vitamin E 400 IE twice a day
Muscle spasm & weakness Spasticity
– Baclofen 5 to 10 mg twice daily to three times daily
– Tizanidine 2 to 4 mg by mouth twice daily up to a total dose of 24 mg daily
– Memantine starting at 5 mg daily, increasing by 5 mg a week to a maximum of 20 mg twice a day
– Tetrazepam 50 mg at bedtime, increasing by 25 mg a day to a maximum dose of 150 mg taken two to three times a day
Pseudobulbar affect
Also known as: pseudobulbar palsy, emotional incontinence, pathologic crying/laughing
The emotional lability is NOT a mood disorder, but is an uncontrolled outburst and is a very troubling symptom for patients.
It is an abnormal affective display that can be seen in about 50% of ALS patients.
Pseudobulbar affect
Amitriptyline 10~150mg QHS Fluvoxamine (Luvox) 100~200mg QD Alternatively may try Lithium or L-Dopa
Constipation
Common symptom due to immobility and side effects from opioid, anti-cholinergics, muscle relaxants
Pain
Often results from muscle contracture, joint stiffness, and immobility leading to pressure ulcers at later stage of disease
Sleep problems
Often associated with other symptoms Identify and treat underlying causes Use sedative cautiously
Dysarthria
Speech therapy often helpful early Computer technology offer many
options to assist with patient communication
Dysphagia and nutrition
Decreased caloric and fluid intake may lead to worsening of symptoms, such as weakness, muscle atrophy, fatigue
Initially management includes the modification of food and liquid consistency
Discussion of possible PEG placement
Dysphagia and nutrition For optimal safety and efficacy, PEG
placement should be performed before the forced vital capacity falls to below 50% of predicted and not in the preterminal phase.
The indications should be to evaluate for symptoms of hunger, choking, sign of inadequate oral intake, and diminished quality of life, rather than a swallow evaluation.
Dysphagia and nutrition Complications for PEG include:
– Transient laryngeal spasm 7.2%– Localized infection 6.6– Gastric hemorrhage 1~4%– Death 1.9%
Does NOT prevent aspiration pneumonia
Studies suggest that with PEG survival is prolonged by 1~4 months
Dysphagia and nutrition AAN Practice Parameters
Respiratory care It is important to initiate discussion
regarding the patient’s goals and how those goal can be best achieved with respect to respiratory care including non-invasive and invasive mechanical ventilation.
Respect the right of patients to refuse or withdraw treatment.
Respiratory care A decrease of VC to <50% is often
associated with respiratory symptoms. A VC of less than 1L or 25~30% of
predicted is associated with significant risk of respiratory failure and sudden death.
There are no current guidelines on how frequently to test VC.
Respiratory care
Dyspnea– Body position such as elevation is often
helpful– Chest physiotherapy in the early phase– Opioid can be used to treat dyspnea and
benzodiazepines for associated anxiety– Inhaled opioids have not consistently
demonstrated benefit; inhaled lidocaine appears to be more efficacious
Oxygen can be administered for hypoxia
Respiratory care Months to years before terminal respiratory
failure, symptoms of chronic nocturnal hypoventilation frequently presents and impair the patient’s quality of life.
The symptoms include: daytime fatigue, concentration difficulty, headache, disturbed sleep, nightmares, nervousness, depression, anxiety, tachypnea, tachycardia, diaphoresis, dyspnea, phonation difficulties, reduced appetite, weight loss, gastritis, cyanosis, edema, recurrent URI, dizziness, syncope, visual disturbance, diffuse pain
Respiratory care Non-invasive intermittent ventilation
administered at night for 4 hours is an efficient way of alleviating nocturnal symptoms.
It should be made clear that this effort is for the purpose of symptom management and improving the quality of life rather than prolongation.
Respiratory care It is important to explore other means of
ventilatory support should it be desired. The goals of such support and when to discontinue such therapies when the goals are no longer being met. Patients need to be reassured that all necessary care will be provided to ensure their comfort.
Non-invasive: Negative pressure body ventilators and oscillators, Intermittent abdominal pressure ventilator, Intermittent positive pressure ventilators (mouth/nasal)
Tracheostomy & ventilation
Patients show higher satisfaction with NIV than IV.
Studies show that ventilator dependent patients are not more depressed than patients who are not vent dependent, and can lead meaningful lives.– But there is greater financial, social and
emotional burden.
Respiratory care
Respiratory care AAN Practice Parameter
Other symptoms
Urinary frequency/urgency– In the absence of UTI, often due to
spasticity that responds well to Oxybutinin Peripheral edema
– Often dependent: elevation, massage, compression hose (r/o DVT)
Laryngospasm– Sudden reflex closure of vocal cords due to
variety of stimuli, usually resolves spontaneously
– H1 and H2 blocking agents may be helpful
Psychosocial and spiritual care
The role of continued support for patient and family cannot be underestimated or overstated.
Bereavement and grief counseling from diagnosis
Additional resources ALS Association (www.alsa.org) Muscular Dystrophy Association (
www.mdausa.org)– Links to resources for patients and families
Books: – Learning to Fall: The Blessings of an
Imperfect Life, Philip Simmons– Tuesdays with Morrie, Mitch Albom
Special considerations in pediatricsusing SMA (spinal muscular atrophy) as a model