title: How common are ALS plateaus and reversals?
abstract: OBJECTIVE
  To determine the frequency of amyotrophic lateral sclerosis (ALS) plateaus and reversals in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.
  
  
  METHODS
  We analyzed Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS-revised (ALSFRS-R) data from PRO-ACT participants. The frequencies of participants experiencing plateaus (periods where scores did not change) were calculated over 6-, 12-, and 18-month epochs. The percentage of participants ever experiencing reversals (periods where scores improved) of different lengths were also calculated and plotted.
  
  
  RESULTS
  Over 6 months, 25% of 3,132 participants did not decline. Over 12 months, 16% of 2,105 participants did not decline. Over 18 months, 7% of 1,218 participants did not decline. Small ALS reversals were also common, especially over shorter follow-up intervals; 14% of 1,343 participants had a 180-day interval where their ALSFRS-R slope was greater than zero. Fewer than 1% of participants ever experienced improvements of 4 or more ALSFRS-R points lasting at least 12 months.
  
  
  CONCLUSIONS
  ALS plateaus and small reversals are common, especially over brief intervals. In light of these data, stable disease, especially for a short period of time, should not be interpreted as an ALS treatment effect. Large sustained ALS reversals, on the other hand, are rare, potentially important, and warrant further study.
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA. Bedla001@mc.duke.edu.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Bedlack
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Vaughan
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Paul
authors.initials: P
authors.lastname: Wicks
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Heywood
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Ervin
authors.initials: E
authors.lastname: Sinani
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Roger
authors.initials: R
authors.lastname: Selsov
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Merit
authors.initials: M
authors.lastname: Cudkowicz
authors.affiliation: From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA.
authors.forename: Alex
authors.initials: A
authors.lastname: Sherman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D018450:Disease Progression; D019317:Evidence-Based Medicine; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008875:Middle Aged; D012042:Registries; D012075:Remission, Spontaneous; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology