Cognitive Functioning in Pediatric Acute Disseminated Encephalomyelitis

Krupp L, Serafin D, Preston T, Christodoulou C, Ackerson J, Benedict R, Brown T, Im-Wang S, Julian L, Parish J, Putnam M, Belman A, Chabas D, Chitnis T, Kuntz N, Ness J, Waubant E, Weinstock-Guttman B, Yeh A,

US Network of Pediatric Multiple Sclerosis Centers

Methods

Objectives / Background Results

Conclusions

Objective: To define cognitive functioning in patients with ADEM.

Background: Acute disseminated encephalomyelitis (ADEM) is an immune mediated inflammatory demyelinating event of the central nervous system characterized by encephalopathy and multifocal neurological deficits. Multiple white matter lesions are present, frequently associated with lesions in deep grey matter. ADEM typically occurs within 30 days of a viral infection or immunization, and more commonly occurs in children more than in adults. Patients typically recover from a single ADEM event (monophasic ADEM) with self-limited disease, although a small subset of patients have subsequent neurological events, or multiphasic forms of the disorder and are often reclassified as MS. Little is known about the subsequent level of cognitive functioning of either those with monophasic ADEM or those with an ADEM-like presentation but eventually reclassified as MS or other disorders (e.g. neuromyelitis optica).

Acknowledgements: Research funded by the NMSS “Pediatric MS Centers of Excellence” Award, NMSS #PP1017 and supported by Stony Brook GCRC (#MO1RR10710). Other Pediatric MS Centers of Excellence are in medical centers at the following institutions: U. Alabama, SUNY-Buffalo, Harvard University, Mayo Clinic, UCSF. Outside Funding Sources: National Multiple Sclerosis Society

Patients. 27 children meeting criteria for ADEM underwent cognitive testing. Patients were drawn from a network of pediatric MS centers located in 6 major medical centers in the United States. There were 11 girls and 15 boys with a mean age of 10.5 ± 3.2 (6-17.7) years. Average interval between the initial ADEM event and the neuropsychological assessment was 38.6 ± 38.0 (0-117) months. In 16/27 (59%) of the children, ADEM was monophasic; 11/27 were followed by another neurologic event. Non-English speaking children, and children with known learning disabilities, ADHD, or pre-existing neurological conditions were excluded . All neuropsychological testing (NP) was done after stabilization of the acute event and at least 4 weeks from the last steroid dose.Measures: All sites did the following abbreviated neuropsychological battery with tests of: general intellect, Wechsler Abbreviated Scale of Intelligence (WASI), sustained attention and impulse control, Conners Continuous Performance test (CPT-II), and learning/verbal memory, California Verbal Learning Test (CVLT –C/CVLT-II). The results were compared to normative data and impairment was defined as a score of at least 1.5 standard deviations below the mean on 1 of any of the variables in the 3 domains.

• 14/28 (50%) displayed cognitive impairment• Of the 16 patients with Monophasic ADEM, 7/16 (44%) were impaired as far out

as 113 months from the first event, mean 24.8 ± 31.3 (0-113) months. • Of the 11 with ADEM followed by subsequent neurologic events . 6/11(54.5%)

were impaired as far out as 117 months from the first event, mean= 69.2 ± 34.3 (16-117) months.

• With respect to the individual measures, impaired functioning was most frequent on the CVLT –C/II (8/27, 30%), followed by the CPT (4/27, 15%) and the WASI (1/27 , 3.7%).

Impaired ADEMN=14

UnimpairedADEMN = 14

Avg. Age at Symptom Onset

(months)

93.9 (±59.0) 83.7 (±38.4)

Avg. Time interval between first event

and NP evaluation (months)

44.5 (±40.9) 32.2 (±35.1) Average Z-Scores on Neurocognitive Tests Administered

Clinical Characteristics

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

Impaired Monophasic

Impaired Multiphasic

Combined Impaired group

Non Impaired

Z-Scores

General Intellect Attention and Impulse Control Learning/Verbal Memory

NP TestsDomain Variables Tested

General Intellect• WASI Full-2 Subtest IQ

• WASI Vocabulary

• WASI Matrix Reasoning

Sustained Attention & Impulse Control

• CPT Commissions

• CPT Omissions

• CPT Hit Response Rate

Learning/Verbal Memory

• CVLT Total Trials (1-5)

• CVLT List A Trial 1

• CVLT List B Trial 1

• CVLT List A Long Delay Free Recall

A substantial proportion of patients with an ADEM-like presentation , including those with and without subsequent neurologic events, show cognitive deficits long after their initial event. In this study memory and attention functions were most affected.Future research on this disorder and its possible cognitive consequences will be an important direction for the National Pediatric Multiple Sclerosis Centers of Excellence.

References 1. Krupp LB, Banwell B, Tenembaum S. Consensus definitions proposed for pediatric multiple

sclerosis and related disorders. Neurology2007 Apr 17;68(16 Suppl 2):S7-12.2. Banwell B,