For Healthcare Professionals
 

Monitoring ALS

ALS is a heterogeneous disease that presents and progresses differently in every patient. Monitoring disease activity is important to assessing functional decline and understanding rate of progression, as this is the ultimate determinant of disease prognosis.
 
monitor ALS progression

Monitoring ALS

ALS is a heterogeneous disease that presents and progresses differently in every patient. Monitoring disease activity is important to assessing functional decline and understanding rate of progression, as this is the ultimate determinant of disease prognosis.
monitor ALS progression
Tracking Disease
Activity
 

Tools to Monitor ALS Progression

Progressive weakness is a hallmark of ALS. However, measuring change in physical function and disease progression has historically been a challenge.

Numerous clinical measures have been developed in an effort to monitor disease progression. Today, common outcome measures used in ALS clinical trials include1
The ALS Functional Rating Scale-Revised (ALSFRS-R) is a validated questionnaire that measures physical function in performing activities of daily living (ADLs).2
Strengths1-4: Weaknesses1,5:
  • Widely accepted measure of disease progression
  • Captures many clinically relevant features of disease progression
  • Focuses on ALS-caused disability
  • Reproducible
  • Easily administered
  • Correlated with QoL
  • Strong predictor of survival
  • Can be administered by telephone
  • Subjective score
  • Does not measure underlying pathophysiology
  • Categorical scale with overall summed score
Death or tracheostomy endpoints are often used interchangeably in clinical trials, as permanent assisted ventilation signifies a severe decline in respiratory function.6
Strength1: Weaknesses1:
  • Undeniably clinically relevant
  • Increases trial duration and cost
  • Provides no information about QoL or disability
  • Confounded by nonuniform application of life-extending interventions*
Assessing respiratory function is essential because respiratory insufficiency remains the main cause of mortality in ALS.7
Strengths1: Weaknesses1:
  • Declines with ALS progression
  • Clincally relevant
  • Related to survival
  • Easily tested
  • Affected later in limb onset
  • Affected earlier in bulbar onset
Because muscle weakness is a major clinical feature of ALS, quantifying a patient's strength over time can help assess physical function.1
Strengths1: Weaknesses1:
  • Quantitatively assesses loss of muscle strength
  • Objective measure
  • Easily transported and reproducible
  • Subject to examiner technique error
  • Extensive training required to ensure intra- and inter-rater reliability
  • Results vary based on patient effort
  • ALSFRS-R
    The ALS Functional Rating Scale-Revised (ALSFRS-R) is a validated questionnaire that measures physical function in performing activities of daily living (ADLs).2
    Strengths1-4:
    • Widely accepted measure of disease progression
    • Captures many clinically relevant features of disease progression
    • Focuses on ALS-caused disability
    • Reproducible
    • Easily administered
    • Correlated with QoL
    • Strong predictor of survival
    • Can be administered by telephone
    Weaknesses1,5:
    • Subjective score
    • Does not measure underlying pathophysiology
    • Categorical scale with overall summed score
  • Tracheostomy-Free Survival
    Death or tracheostomy endpoints are often used interchangeably in clinical trials, as permanent assisted ventilation signifies a severe decline in respiratory function.6
    Strength1:
    • Undeniably clinically relevant
    Weaknesses1:
    • Increases trial duration and cost
    • Provides no information about QoL or disability
    • Confounded by nonuniform application of life-extending interventions*
  • Vital Capacity1
    Assessing respiratory function is essential because respiratory insufficiency remains the main cause of mortality in ALS.7
    Strengths1:
    • Declines with ALS progression
    • Clincally relevant
    • Related to survival
    • Easily tested
    Weaknesses1:
    • Affected later in limb onset
    • Affected earlier in bulbar onset
  • Hand-held Dynamometry
    Because muscle weakness is a major clinical feature of ALS, quantifying a patient's strength over time can help assess physical function.1
    Strengths1:
    • Quantitatively assesses loss of muscle strength
    • Objective measure
    • Easily transported and reproducible
    Weaknesses1:
    • Subject to examiner technique error
    • Extensive training required to ensure intra- and inter-rater reliability
    • Results vary based on patient effort
The ALSFRS-R Scale
 

ALSFRS-R: The Gold Standard of
Quantifying Disease Progression in ALS Clinical Trials8

ALSFRS-R is a widely used test in clinical trials for measuring and evaluating decline in physical function over time in ALS patients.2,4

The ALSFRS-R is a validated, questionnaire-based instrument that
ALS physical function
Measures physical function in carrying out activities of daily living (ADL)2
ALS test
Assesses bulbar, fine motor, gross motor, and respiratory functions2
ALS and disability
Correlates with objective measures of disease status and level of disability2
ALS clinical trials
Is frequently used in ALS clinical trials and recommended in treatment guidelines2,9
ALSFRS-R test
Is a simple, convenient, and easily reproducible measure that can be administered online or over the phone1,4
While other clinical tools are specific to certain disease 
features – such as respiratory or muscle function – 
the ALSFRS-R scale provides a comprehensive 
measure of physical function.

The ALSFRS-R Has Been Refined Over the Years

The ALSFRS-R has been in use since 1991 and has evolved throughout the years, so there are extensive data regarding its utility and reproducibility over time.

Today, the ALSFRS-R is a widely used tool in clinical trials to assess disease progression.4
test for ALS began in 1991

ALSFRS development begins


Need for easily administered clinical rating instrument to monitor patients in clinical practice and serve as outcome for clinical trials10
ALS functional rating scale revised to ALSFRS-R in 1999

ALSFRS revised to ALSFRS-R2


Added 3 additional questions to balance respiratory functions with limb strength and bulbar functions10
ALSFRS-R clinical relevance established in 2009

Proposed clinical relevance of measure10


20% to 25% change in the decline of the ALSFRS-R scale represents a clinically relevant effect*
ALSFRS-R measures ALS progression today

ALSFRS-R widely accepted as measure of ALS progression4


A validated primary outcome measure used by clinical trialists and regulatory bodies2,9
ALS history 1991

ALSFRS development begins


Need for easily administered clinical rating instrument to monitor patients in clinical practice and serve as outcome for clinical trials10
ALS history 1999

ALSFRS revised to ALSFRS-R2


Added 3 additional questions to balance respiratory functions with limb strength and bulbar functions10
ALS history 2009

Proposed clinical relevance of measure10


20% to 25% change in the decline of the ALSFRS-R scale represents a clinically relevant effect*
ALS today

ALSFRS-R widely accepted as measure of ALS progression4


A validated primary outcome measure used by clinical trialists and regulatory bodies2,9
*As rated by 93% of the 65 members of the Northeast ALS Consortium (NEALS) clinical investigators.
How the ALSFRS-R
Works
 

How Does ALS Testing Measure Disability Progression?

The ALSFRS-R measures 12 aspects of physical function categorized within 4 functional domains (bulbar, fine motor, gross motor, and respiratory).

Each aspect of function is scored from 4 (normal) to 0 (no ability). The maximum total score is 48, and the minimum total score is 0.
ALS types chart
Variability of
Results
 

Each ALSFRS-R Score Is Unique to the Patient

The heterogeneity of disease spread and rate of progression mean that the ALSFRS-R score remains individual in nature. Two patients with similar overall scores can still exhibit very different symptoms.6

For example, while Patient A primarily experiences symptoms of the bulbar and cervical regions, Patient B experiences symptoms of the lumbar region and exhibits respiratory complications. Both have ALSFRS-R scores of 40.
ALSFRS-R scoring
ALSFRS score meaning
Understanding an individual’s unique course of disease 
will help you provide personalized care tailored to 
their specific needs.
References: 1. Berry JD, Cudkowicz ME. New considerations in the design of clinical trials for amyotrophic lateral sclerosis. Clin Investig (Lond). 2011;1(10):1375-1389. 2. Cedarbaum JM, Stambler N, Malta E, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. J Neurol Sci. 1999;169(1-2):13-21. 3. Beghi E, Mennini T, Bendotti C, et al. The heterogeneity of amyotrophic lateral sclerosis: a possible explanation of treatment failure. Curr Med Chem. 2007;14(30):3185-3200. 4. Leigh PN, Swash M, Iwasaki Y, et al. Amyotrophic lateral sclerosis: a consensus viewpoint on designing and implementing a clinical trial. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5(2):84-98. 5. Swash M. New ideas on the ALS functional rating scale. J Neurol Neurosurg Psychiatry. 2017;88(5):371-372. 6. Simon NG, Turner MR, Vucic S, et al. Quantifying disease progression in amyotrophic lateral sclerosis. Ann Neurol. 2014;76(5):643-657. 7. Amyotrophic lateral sclerosis (ALS) fact sheet. National Institute of Neurological Disorders and Stroke website. https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/amyotrophic-lateral-sclerosis-als-fact-sheet. Published June 2013. Accessed April 13, 2017. 8. Eisen A. Motor neurone disease. In Turner MR, Kiernan MC, eds. Landmark Papers in Neurology. 1st ed. Oxford, United Kingdom: Oxford University Press; 2015:264. 9. The American Academy of Neurology. The care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies. https://www.aan.com/guidelines/home/getguidelinecontent/373. Accessed May 1, 2017. 10. Castrillo-Viguera C, Grasso DL, Simpson E, et al. Clinical significance in the change of decline in ALSFRS-R. Amyotroph Lateral Scler. 2010;11(1-2):178-180.