US Network Longitudinal Study of Cognitive Functioning in Pediatric MS, AAN, 2014

Objective

To assess longitudinal changes in cognitive function among individuals with pediatric MS evaluated within the US Network of Pediatric MS Centers

BackgroundMS onset prior to age18 years has an estimated incidence of:

0.2-0.6/100,000

Cognitive impairment occurs in approximately 1/3 of those with pediatric MS

McAllister et al. 2005 (n=37) 35% Amato et al. 2008 (n=63) 31%Till et al. 2011(n= 35) 29% Julian et al. 2012, (n=231) 32%

Longitudinal studies are few

Amato et al. 2010: Two-year f/u (n=56), compared to controls

75% worsened on a Cognitive Change Index

Till et al. 2013: One-year f/u (n=28) compared to controls

Groups differed in rate of improvement MS improved on 18% of measures vs Controls on 86% Using RCI, decline occurred in 23% MS vs 4% of

Controls

Methods

The US Network consists of 9 pediatric MS centers sharing a common database

Baseline and f/u cognitive testing 18 months later was administered across 6 sites

Participants had MS or CIS and be were 30 or more days free of a relapse and last steroid dose

Cognitive Test Battery

General Intelligence (WASI)

2 subtest IQ

Simple Attention (Digit Span)

Digits Forward

Digits back

Visuo-motor skill Beery (Visual-Motor Integration Test)

Language (Expressive One-Word Vocabulary)

Cognitive Test Battery

WIAT-II Pseudoword decoding

Verbal Memory California Verbal Learning Test (CVLT-C/CVLT-II )

Total learning across trials

Total long-delay free recall

D-KEFS Trail Making Test

Visual Scanning

Number Sequence

Letter Sequence

Letter-Number Sequence

Motor Speed

Study Cohort53 MS, 7CIS

Age at first evaluation (NP1) Mean = 14.36±1.95 years

range (8.11 to 17.77 years)

Time between baseline (NP1) and follow-up testing (NP2)

Mean = 1.54 years ± 0.56 (0.75 to 2.99 years)

Cohort Demographic Features N = 60; 21 male (35%), 39 female (65%) Race

White n=46 (76.7%) African-American n=12 (20%) Asian n=1 (1/7%) Other n=1 (1.7%)

Ethnicity: Hispanic=18 (30%) Non-Hispanic 28 (70%)

Maternal years of education: Mean =13.8 ±2.2 years (7 - 18 yrs)

Cohort Clinical Features

Symptom duration at NP1Mean =1.36 ± 1.66 years

(.09 to 8.32 years)

EDSS at NP1Mean=1.48 ±1.21 (0 to 6)

EDSS at NP2Mean = 1.19 ± 1.40 (0 to 4.5)

EDSS NP1 vs. EDSS NP2 ns (p=0.35)

Performances on individual measures at NP1 and NP2

-1

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

WASI 2DSFWDDSBACKEOWPWDLIST A TOT LD FREEVISSCANNUM SCANLETTER SEQLETTER NUMBERMOTOR SPEEDVMI

Baseline Follow-Up

Mean z

score

, n=

60

Average percentage of impaired tests per subject

Percent of test scores <1 SD published norm/patient

NP1: 27% ±21% (range 0 - 86%)

NP2: 26% ±21% (range 0-78%)

Number of impaired tests

Sum of impaired tests at baselineMean 4.23 ±-2.99 (0 to 12

Sum of impaired tests at follow-upMean 4.00 ±-3.00 (0 to 11)

Change in sum of impaired tests-4.00 to 5, mean -.017 ± 1.95

Change in total number of impaired tests

Cognitive Change Index (CCI)

Most patients showed no change

Declined on 2 or more tasks n=8 (13.3%)

Improved on 2 or more tasks n=12 (20%)

No clear pattern of improvement or decline on any test, in any area

Change was not related to any clinical or demographic features

Comparisons with other studies

Amato et al. (2010):

Greater proportion of low IQs

28% vs. only 1 patient in this cohort

20-40% had language problems (with more language measures in battery)

No indication of language impairment or decline in this cohort

More time between testing (18 months vs. 24 months)

Other studies

Till et al. (2013)Lower rate of decline consistent with

findings from our cohortAbsence of expected age-related gainsNatural history control group is needed,

Conclusions

Cognitive impairment remains relatively stable for most children

Relative cognitive stability is present over similar intervals in adult MS

Nonetheless, pediatric MS patients may not be achieving age-expected cognitive gains