James Wymer, MD, PhD

Dr Chuquilin is Assistant Professor, Dr. Wyman is Professor, Department of Neurology, University of Florida, Gainesville, FL.

Amyotrophic lateral sclerosis (ALS) has an incidence of 1.5-2.7/100 000 and a prevalence of 3-5/100 000. The lifetime risk of ALS is approximately 1:350 for men and 1:400 for women.

 About 90% of ALS cases are sporadic, with no family history and 10% are familial (mostly dominant). The most common familial form is caused by mutations in the 

 gene causing multiple hexanucleotide (GGGGCC) repeat expansions. To date, there is no cure for ALS and treatment focuses on improving quality of life, slowing disease progression, and improving survival.

Disease progression and the effect of the disease on the patient’s daily activities is monitored using the ALS-Functional Rating Scale (ALS-FRS). This scale includes 12 questions, with scores ranging from 0 to 4 (best score is 48). It is a commonly accepted scale for use in clinical trials.

Multidisciplinary ALS evaluation and follow up

Patients with ALS benefit from an ALS multidisciplinary clinic. They receive comprehensive care from a neurologist, physical therapist, occupational therapist, speech therapist, respiratory therapist, dietician, social worker, and durable medical equipment expert. ALS patients that receive care at multidisciplinary centers have better quality of life, satisfactions with their care, and survival.

 In a multidisciplinary clinic setting, behavioral changes or cognitive impairment (present in up to 40% to 50% of cases), can be properly diagnosed and monitored.

Respiratory failure is the most common cause of death in patients with ALS. As the disease progresses the forced vital capacity (FVC) of the patient decreases. FVC value is insensitive to detect early respiratory failure, as 13 of 20 patients with an FVC higher than 70% had abnormal maximal inspiratory pressure (MIP) lower that -60 cm H20. Nocturnal desaturations lower than 90% for 1 cumulative minute is a more sensitive indicator of nocturnal hypoventilation than FVC or maximum inspiratory pressure.

Once patients develop orthopnea, FVC drops to less than 50%, MIP is lower than -60 cm or if patient has nocturnal desaturations, they should be started on noninvasive ventilation (NIV). The use of NIV has been shown to increase survival in ALS patients by a median of 205 days in one randomized controlled study.

 Findings from a case study also indicate that NIV  improved quality of life.

It is important to note that the disease continues to progress and eventually patients will require tracheostomy and full-time ventilation. This is a decision that has to be made by the patient after careful discussion with the clinical provider and family members. Not everyone decides to go this route.

Percutaneous endoscopic gastrostomy tube placement

ALS leads to inability to swallow and chew with risk of aspiration, weight loss, and dehydration. One manifestation of ALS is a hypermetabolic state, and decreased oral intake further exacerbates weight loss.

 There is an association between body-mass index (BMI) and survival in ALS patients. Low BMI (<10.5 kg/m

) is associated with shorter survival and moderate obesity (BMI 30-35) is associated with slower disease progression and longer survival.

 Frequent swallow evaluation is needed to assess if it is within functional limits or if it needs to be supplemented by other means such as altering food consistency and chin tuck maneuver.

Eventually, when swallowing is no longer functional or if the patient has lost more than 10 % of his or her weight, a discussion about percutaneous endoscopic gastrostomy tube (PEG) placement is needed. This does not eliminate oral feeding, but provides a more convenient way of administering medication and fluid and stabilizing weight.

 PEG tube helps ALS patients receive the calories they need to prevent malnourishment and dehydration and stabilizes their weight. PEG tube placement is a procedure that is better performed when vital capacity is greater than 50%, procedure risks increases with anything below that value.

Two medication are FDA-approved for ALS. They are not curative, but slow disease progression. The first is riluzole, which is a glutamate receptor antagonist. In a randomized placebo controlled trial, riluzole improved survival time (defined as time to death or tracheostomy) by an average of 3 months. The patients included in this study had symptoms for less than 5 years, FVC higher than 60%, and had not had a tracheostomy. A subgroup with bulbar symptoms showed more improvement. The dose was 50 mg PO twice a day. Adverse effects included asthenia, stiffness, nausea, abdominal pain, and elevated liver function tests.

 The benefits of riluzole were also seen in other studies.

 A larger survival effect was seen in case reports, but those studies are subject to more bias.

The most recently approved drug therapy is edaravone, which is a free-radical scavenger. In a placebo-controlled study in a selected ALS patient population (< 2 years diagnosis, FVC > 80%, score of 2 points or better in each ALS-FRS score question), edaravone slowed the rate of decline of the ALS-FRS score by 33% over 6 months compared with placebo. The authors did not comment on survival effect. This medication is administered as an infusion in 14 consecutive days for the first month, then for 10 days (in a 14 day period) from the second month thereafter. The infusion time is about 1 hour and requires the placement of a port catheter for ease of administration and can occur at home or at infusion centers.

 Adverse effects include allergic reactions, sulfite allergic reactions, bruising, and headache. This medication was approved for all ALS patients, not just those meeting study criteria.

Pseudobulbar affect (excessive or inappropriate laughing, crying, yawning) can affect 20% to 50% of ALS patients and can be socially inadequate or embarrassing. A combination of dextromethorphan/quinidine 30/30 mg BID is effective in reducing the frequency and severity of laughing and crying behaviors. Adverse effects include dizziness, nausea and somnolence.

As mentioned above, patients with ALS also develop sialorrhea. In some patients, sublingual atropine drops can help. Other options include tricyclic antidepressants such as amitriptyline or anticholinergics such as glycopirrolate. In other cases, salivary gland botulinum toxin injections have been proved to be effective.

 Fatigue is also an undertreated ALS symptom. Its origin is likely multifactorial from muscle weakness, reduced endurance and can be treated with modafinil.

Although there is no cure for ALS, there are treatments available that can improve the quality of life and prolong survival (

). A multidisciplinary approach is key in the care of this population.

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 Amyotroph Lateral Scler Frontotemporal Degener

10. Kasarskis EJ, Scarlata D, Hill R, et al. A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials. 

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Articles

Although there is no cure for ALS, there are treatments available that can improve the quality of life and prolong survival.

James Wymer, MD, PhD

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Caring for Patients With ALS: A Brief Review