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Sections Amyotrophic Lateral Sclerosis
- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Inpatient and Outpatient Care
- Pharmacologic Treatment
- Treatment of Symptoms
- Ventilatory Support
- Dietary Considerations
- Activity Restriction
- Alternative Therapies
- Informing Patients of the Diagnosis
- Patient Support and Advice
- Consultations
- Long-Term Monitoring
- Prevention
- Show All
- Guidelines
- Medication
- Questions & Answers
- Media Gallery
- Tables
- References
Guidelines Summary
In October 2009, the American Academy of Neurology (AAN) published a 2-part, evidence-based Practice Parameter update about the care of patients with ALS. [2, 3] These publications updated the 1999 evidence-based practice parameter. [173]
NIV, PEG, and riluzole
The chief findings of the practice parameter are that for extending life or slowing disease progression, the evidence is best for use of noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole. The authors comment that these treatments are often underutilized and recommend that they should be offered to patients, in the case of riluzole, or considered by the physician, in the case of NIV and PEG.
The median extension of life by riluzole in placebo-controlled studies was 2-3 months. The median extension of life by NIV or PEG may be approximately 6 months, provided the treatments are applied early and adhered to. The efficacy of NIV is supported by a randomized, controlled trial. [187]
Multidisciplinary care
The authors also recommend that referral to a multidisciplinary clinic should be considered for managing patients with ALS. Such clinics can optimize healthcare delivery, prolong survival, and enhance quality of life.
Botulinum toxin
In patients with sialorrhea that is refractory to treatment with standard medications, botulinum toxin B injection of the salivary glands should be considered. Alternatively, low-dose radiation therapy to the salivary glands may be considered.
Botulinum toxin for ALS carries a manufacturer's warning regarding possible spread of the toxin to ventilatory muscles (leading to exacerbation of ventilatory failure) or bulbar muscles (exacerbating their weakness). The risk of these adverse effects tilts the balance in terms of safety toward salivary gland irradiation, except in patients with exceptional ventilatory and bulbar reserves.
Dextromethorphan and quinidine
Finally, the guideline recommends that dextromethorphan and quinidine be considered for pseudobulbar affect. A combination of dextromethorphan and quinidine (Nuedexta) has shown efficacy in ameliorating involuntary laughter and crying (the expression of pseudobulbar affect). [186, 187] It has FDA approval for this indication.
Clinician and patient summaries of the AAN guidelines are available on the AAN website:
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Fang T, Al Khleifat A, Stahl DR, Lazo La Torre C, Murphy C, Uk-Mnd LicalS, et al. Comparison of the King's and MiToS staging systems for ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2017 May. 18 (3-4):227-232. [QxMD MEDLINE Link].
Aggarwal SP, Zinman L, Simpson E, McKinley J, Jackson KE, Pinto H, et al. Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 May. 9 (5):481-8. [QxMD MEDLINE Link].
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The 4 regions or levels of the body. Bulbar (muscles of the face, mouth, and throat); cervical (muscles of the back of the head and the neck, the shoulders and upper back, and the upper extremities); thoracic (muscles of the chest and abdomen and the middle portion of the spinal muscles); lumbosacral (muscles of the lower back, groin, and lower extremities).
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The genetic/environmental/age- and time-dependent interactions hypothesis for amyotrophic lateral sclerosis (ALS). Risk factors operate upstream to a putative biochemical transformation (likely an acquired nucleic acid or protein change), which causes the appearance of altered proteins or nucleic acids or abnormal quantities of normal proteins or nucleid acids. These agents spread within the motor system and cause the downstream disintegration of the motor system and the downstream biochemical, histologic, and clinical consequences of ALS. (Adapted from Armon C. What is ALS? In: Amyotrophic Lateral Sclerosis: A Patient Care Guide for Clinicians. Bedlack RS, Mitsumoto H, Eds. Demos Medical Publishing, New York, 2012:1-23)
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Muscle in nerve disease. Image courtesy of Dr. Friedlander, Associate Professor and Chair of Pathology at Kansas City University of Medicine and Biosciences.
Tables
Gene |
Locus |
Protein |
Inheritance |
SOD1 (ALS1) |
21q22.11 |
Superoxide dismutase 1 (SOD1) |
AD* |
ALS2 |
2q33 |
Alsin (ALS2) |
Juvenile/AR** |
ALS3 |
18q21 |
Unknown |
AD |
ALS4 |
9q34 |
SETX |
Juvenile/AD |
ALSS |
15q15 |
SPG11 |
Juvenile/AR |
FUS (ALS6) |
16p11.2 |
FUS |
AD |
ALS7 |
20ptel-p13 |
Unknown |
AD |
ALS8 |
20q13.3 |
VABP |
AD |
ALS9 |
14q11.2 |
Angiogenin (ANG) |
AD |
TARDBP (ALS10) |
1p36.2 |
TAR DNA-binding protein (TARDBP) |
AD |
ALS11 |
6q21 |
FIG4 |
AD |
ALS12 |
10p13 |
OPTN |
AD; AR |
ALS13 |
12q24 |
ATXN2 |
AD |
ALSX |
Xp11 |
UBQLN2 |
X-linked |
C9orf72 (ALS-FTD) |
9q21-22 |
C9ORF72 |
AD |
ALS-FTD |
9p13.3 |
SIGMAR1 |
AD; Juvenile/AR |
PFL1 |
17p13.2 |
Profilin 1 |
AD |
*AD–autosomal dominant; **AR—autosomal recessive |
|||
Carmel Armon, MD, MSc, MHS Chair, Department of Neurology, Assaf Harofeh Medical Center, Tel Aviv University Sackler Faculty of Medicine, Israel
Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Sigma Xi, The Scientific Research Honor Society
Disclosure: Received research grant from: Neuronix Ltd, Yoqnea'm, Israel<br/>Received income in an amount equal to or greater than $250 from: JNS - Associate Editor. UpToDate - Author Royalties.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Nicholas Lorenzo, MD, CPE, MHCM, FAAPL Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Former Chief Medical Officer, MeMD Inc
Nicholas Lorenzo, MD, CPE, MHCM, FAAPL is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for Physician Leadership
Disclosure: Nothing to disclose.
Neil A Busis, MD Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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