Diagnosis of ALS

Educational Objectives

The goal of this program is to improve the management of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). After hearing and assimilating this program, the clinician will be better able to:

1. Educate and inform patients, families, and the public about ALS.

2. Use the Red Flag tool to speed the diagnosis of possible ALS.

3. Refer appropriate patients for specialty care in a timely fashion.

Summary

Definition of weakness: motor system — begins in cortex, continues down corticospinal tract to anterior horns, then to motor nerves and neuromuscular junction, and ends in muscle; weakness occurs if connection broken anywhere in chain; defined as reduction in strength; patients often claim weakness, but actually fatigued or feel tired, unwell, or listless; these symptoms possible in amyotrophic lateral sclerosis (ALS), but specific symptom of weakness increases likelihood of disease; ALS characterized by death of upper and lower motor neurons

Characteristics of motor neuron disease/ALS: nomenclature — ALS common name in United States; motor neuron disease (MND) used in United Kingdom; ALS also known as Lou Gehrig disease, and as Charcot disease in Europe; presentation — gradual progression of weakness slower than subacute, but not extremely slow; onset may occur in bulbar (facial or swallowing) region or in limbs; patients eventually die because of inability to breathe, unless supported by artificial ventilation; etiology/epidemiology — ALS uncommon; number of persons living with ALS not many times number of persons developing disease, because life span significantly shortened; etiology generally unknown; peak incidence occurs in persons 70 to 80 yr of age, then decreases; prognosis — survival from onset of symptoms to death usually only several years; life expectancy in women often shorter than in men (possibly because onset in women tends to occur in bulbar area); older patients also tend to have more rapid course; multiple mechanisms faulty in motor neurons, but most important mechanisms not known

Genetics of ALS: many recent discoveries; superoxide dismutase (SOD) gene — identified in early 1990s; ≈1% of patients with sporadic ALS have this gene; C9orf72 gene — mutation found in 2010; seen in 5% to 7% of patients with sporadic ALS; C9 mutation causes >60% of ALS in patients with dominantly inherited, familial disease (with some contribution from several other genes); C9 gene also cause of frontotemporal dementia; may confer some increased risk for other neurodegenerative diseases

Determining whether painless weakness represents ALS: Red Flag Tool for diagnosis of MND — purpose of tool to help hasten diagnosis of ALS; benefits of early diagnosis — better care; access to resources of local ALS association; aids in patients understanding cause of their weakness; improved planning for care and support; early diagnosis also increases amount and quality of ALS research

Onset in limbs: most common; patients typically deny pain, but no longer have strength to perform everyday tasks; weakness usually localized; patients describe inability to control fingers and/or loss of fine-motor dexterity (upper motor neuron symptom), heaviness of foot or leg, dragging of foot, or falling (common early symptom); consider ALS in patients with foot drop or muscle cramps (presenting symptom in up to one-third of patients)

Bulbar onset: slurring words/dysarthria most common presentation; patients note difficulty swallowing (liquids more problematic than solid food, but either can cause difficulty); drooling also seen because of swallowing difficulties; symptoms often worsened by lying flat; tongue fasciculations (tongue twitching/flickering) uncommon as presenting complaint but often seen on physical examination; ALS most common cause; ≈25% of patients present with bulbar symptoms

Respiratory onset: presenting symptoms in ≈5% of patients; patients may have fatigue or excessive daytime sleepiness, often due to nighttime retention of carbon dioxide; breathlessness associated with decreasing amounts of activity over time; eating meals becomes more difficult; orthopnea commonly occurs with weakness of diaphragm; breathing easier in upright position vs lying flat

Cognitive changes: common in ALS, but generally mild; only ≈5% of patients develop frank dementia (most persons who develop significant cognitive difficulties had some changes before presenting with ALS); if dementia present, frontal lobe type; usually not amnestic, but consists of difficulties in word finding, spelling, and decision making, apathy, and (rarely) inappropriate behavior; emotional lability/pseudobulbar affect occurs in ≈50% of patients; usually not severe enough to require treatment, but medications available

Progression of disease: look for progression of symptoms when considering diagnosis of ALS; symptoms should progress gradually, rather than stepwise or on-and-off, although patients may experience some fluctuation (symptoms often better in mornings than in evenings); patients can often recall threshold event when specific motor function lost

Additional features: asymmetric — ALS rarely symmetric unless in bulbar region; age — can occur at any age, but more likely in eighth decade of life; risk — family history of ALS or other neurodegenerative disease increases risk; bowel or bladder — urgency commonly seen in patients with ALS, but incontinence uncommon; sensory symptoms — patients do not have sensory symptoms beyond those seen in patients without ALS; dense sensory loss not seen; double vision not seen; prognosis — patients not expected to improve

Referral: consider referral to ALS center if diagnosis seems possible given patient’s history and symptoms (label referral as “possible ALS” rather than according to symptom to speed evaluation); appropriate referral sometimes delayed because of referral to other specialists who later refer to ALS clinic; ALS care must be team effort for optimal care

Readings

Chio A et al: Extensive genetics of ALS: A population-based study in Italy. Neurology 2012 Nov 6; 79(19): 1983-1989; EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis: EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) — revised report of an EFNS task force. Eur J Neurol 2012 Mar;19(3):360-75; Knibb JA et al: A clinical tool for predicting survival in ALS. J Neurol Neurosurg Psychiatry 2016 Jul 4. pii: jnnp-2015-312908 [Epub ahead of print]; Lattante S et al: Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD). Trends Genet 2015 May;31(5):263-73; Shatunov A et al: Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol 2010 Oct;9(10):986-94; Turner MR, Talbot K: Mimics and chameleons in motor neuron disease. Pract Neurol 2013 Jun;13(3):153-64; Williams JR et al: Diagnosis pathway for patients with amyotrophic lateral sclerosis: retrospective analysis of the US Medicare longitudinal claims database. BMC Neurol 2013 Nov 4;13:160.

Disclosures

For this program, the following has been disclosed: Dr. Oskarsson reported nothing to disclose. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Oskarsson was recorded at ALS 2016, Diagnosis to Death, and New Hope, held April 2, 2016, in Sacramento, CA, and presented by the ALS Association and the Office of Continuing Medical Education, University of California, Davis, School of Medicine. For information on upcoming CME programs from the University of California, Davis, School of Medicine and the ALS Association, please visit ucdmc.ucdavis.edu/cme and alsa.org.The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

NE072201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.