Incidence of acquired demyelination of the

CNS in Canadian children

B. Banwell, MD ABSTRACT
J. Kennedy, MSc Background: The incidence of acquired demyelination of the CNS (acquired demyelinating syn-
D. Sadovnick, PhD dromes [ADS]) in children is unknown. It is important that physicians recognize the features of
D.L. Arnold, MD ADS to facilitate care and to appreciate the future risk of multiple sclerosis (MS).
S. Magalhaes, MSc
Objective: To determine the incidence, clinical features, familial autoimmune history, and acute
K. Wambera, MD
management of Canadian children with ADS.
M.B. Connolly, MB,
BCh Methods: Incidence and case-specific data were obtained through the Canadian Pediatric Surveil-
J. Yager, MD lance Program from April 1, 2004, to March 31, 2007. Before study initiation, a survey was sent
J.K. Mah, MD to all pediatric health care providers to determine awareness of MS as a potential outcome of
N. Shah, MD ADS in children.
G. Sebire, MD Results: Two hundred nineteen children with ADS (mean age 10.5 years, range 0.66 –18.0 years;
B. Meaney, MD female to male ratio 1.09:1) were reported. The most common presentations were optic neuritis
M.-E. Dilenge, MD (ON; n ⫽ 51, 23%), acute disseminated encephalomyelitis (ADEM; n ⫽ 49, 22%), and transverse
A. Lortie, MD myelitis (TM; n ⫽ 48, 22%). Children with ADEM were more likely to be younger than 10 years,
S. Whiting, MD whereas children with monolesional ADS (ON, TM, other) were more likely to be older than 10
A. Doja, MD years (p ⬍ 0.001). There were 73 incident cases per year, leading to an annual incidence of 0.9
S. Levin, MD per 100,000 Canadian children. A family history of MS was reported in 8%. Before study initia-
E.A. MacDonald, MD tion, 65% of physicians indicated that they considered MS as a possible outcome of ADS in
D. Meek, MD children. This increased to 74% in year 1, 81% in year 2, and 87% in year 3.
E. Wood, MD Conclusion: The incidence of pediatric acquired demyelinating syndromes (ADS) is 0.9 per 100,000
N. Lowry, MD Canadian children. ADS presentations are influenced by age. Neurology® 2009;72:232–239
D. Buckley, MD
C. Yim, MD GLOSSARY
M. Awuku, MD ADEM ⫽ acute disseminated encephalomyelitis; ADS ⫽ acquired demyelinating syndromes; CI ⫽ confidence interval;
C. Guimond, MSc CPSP ⫽ Canadian Pediatric Surveillance Program; mono-ADS ⫽ monolesional presentation; MS ⫽ multiple sclerosis; ON ⫽
optic neuritis; OR ⫽ odds ratio; poly-ADS ⫽ polylesional presentation; TM ⫽ transverse myelitis.
P. Cooper, MD
F. Grand’Maison, MD
Multiple sclerosis (MS), characterized by relapses of neurologic dysfunction and MRI evidence
J.B. Baird, MD
of inflammatory lesions, is a common cause of neurologic disability among Canadian young
V. Bhan, MD
A. Bar-Or, MD
adults. The onset and diagnosis of MS in children and adolescents is being increasingly recog-
nized.1
MS diagnosis requires evidence of dissemination of inflammatory demyelination within the
Address correspondence and CNS and over time. A first attack of demyelination, or an acquired demyelinating syndrome
reprint requests to Dr. Brenda
Banwell, Research Institute, The (ADS), may occur as a transient illness or may represent the first attack of MS. ADS can be
Hospital for Sick Children, 555 subdivided clinically into acute disseminated encephalomyelitis (ADEM), characterized by
University Ave., Toronto,
Ontario, M5G 1X8 Canada polyfocal deficits and encephalopathy; and clinically isolated syndromes, monofocal or polyfo-
brenda.banwell@sickkids.ca cal deficits without encephalopathy.2
The incidence of ADS in children is largely unknown, particularly because available studies
tend to focus on only specific ADS presentations, such as ADEM,3,4 transverse myelitis (TM),5 or

Authors’ affiliations are listed at the end of the article.

This study was funded by the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation and was performed in
conjunction with the Canadian Paediatric Society Surveillance Program.
Disclosure: The authors report no disclosures.

232 Copyright © 2009 by AAN Enterprises, Inc.

optic neuritis (ON).6,7 Prospective studies of
children with ADS have shown that 16% to
25% are ultimately diagnosed with MS before
age 18 years,8-10 emphasizing the importance of
considering MS risk in this population.
We defined the incidence and clinical
and demographic features of ADS in Cana-
dian children. Data were acquired through
the Canadian Pediatric Surveillance Pro-
gram (CPSP), an innovative national pro-
gram designed to increase awareness of
childhood disorders among Canadian pedi-
atricians and pediatric subspecialists. Since
its inception in 1996, the CPSP has pro-
vided surveillance of more than 34 pediatric
disorders, including several neurologic con-
ditions,11,12 and has facilitated knowledge
translation through annual publications.13
METHODS Prestudy questionnaire and education
materials. Before initiation of the 3-year surveillance study, a
detailed educational overview of pediatric ADS, including defi-
nitions for each of the clinical presentations, and a prestudy
questionnaire were mailed to 2,445 Canadian pediatric health
care providers. The questionnaire consisted of the following
three questions:
1. In the past 2 years, have you cared for any patient less than 18
years of age with acquired demyelination of the CNS?
2. Did you consider the possibility that the child might develop
recurrent demyelination such as MS?
3. Were any of these children subsequently diagnosed with MS?
CPSP program. The CPSP uses a two-tiered reporting system.
Each month, an initial reporting form is mailed to approxi-
mately 2,400 pediatric health care providers. A detailed report-
ing form is completed for each patient identified. Summaries of
reporting practices and study highlights are published
annually.14-16
Surveillance study. From April 1, 2004, to March 31, 2007,
Canadian pediatricians and pediatric subspecialists (including
child neurologists and pediatric ophthalmologists) received a
monthly questionnaire asking them to reply with the age and sex
of any child with ADS, or to indicate that they had not seen
patients meeting the inclusion criteria during the month.
A detailed reporting form was then mailed to all respondents
asking the following: clinical features (a predesigned list was in-
cluded on the reporting form), age at ADS, sex, country of birth,
country of birth of the parents, history of immunization 1
month before ADS onset, family history of MS or other autoim-
mune disease in first and second generation relatives, presence or
absence of white matter lesions on brain MRI, acute therapies,
and duration of therapy. Physicians were asked whether they had
considered the possibility of MS and whether they had discussed
this possibility with the child and family.
Inclusion and exclusion criteria. Patients had to be
younger than 18 years, had to be Canadian residents, and had to
have had no prior history of CNS demyelination. For inclusion,
at least one of the following was required:
1. ON: defined by acute or subacute visual loss, typically associ-
ated with a relative afferent pupillary defect, restricted visual
fields, pain with ocular movement, and with optic nerve
swelling, abnormal signal or enhancement on CT or MRI of
the orbits17.
2. TM: defined by weakness of the limbs, typically associated
with a defined spinal sensory level, bladder or bowel dysfunc-
tion, and MRI evidence of spinal cord swelling, increased
signal, or enhancement; spinal cord compression by extrinsic
or intrinsic lesions was excluded.18
3. ADEM: defined by polylesional neurologic deficits, accompa-
nied by encephalopathy (excessive irritability, somnolence, or
coma).2
4. Monolesional demyelination (mono-ADS other): defined by
neurologic deficits referable to a single CNS site distinct from
the optic nerve or spinal cord.
5. Polylesional demyelination (poly-ADS): defined by multiple
neurologic deficits implicating concurrent involvement of
more than one site in the CNS in the absence of encepha-
lopathy.
The CPSP identified potential duplicate reports through
careful screening of city and month of reporting, and age (in
years) and sex of identified patients. Reporting physicians were
contacted directly, duplicate cases were excluded, and only the
primary physician involved in the care of the child completed the
detailed reporting form.
One author (B.B.) reviewed all detailed reporting forms to
ensure that each patient met inclusion criteria, and to categorize
the clinical presentation as ON, TM, ADEM, mono-ADS other,
or poly-ADS.
It was specifically noted whether children experienced fever
or seizures during their ADS presentation. Children were ex-
cluded if they had culture-proven bacterial meningitis, viral en-
cephalitis, demyelination of the peripheral nervous system (i.e.,
Guillain-Barré syndrome, chronic inflammatory demyelinating
polyneuropathy), biochemical or radiologic suspicion of inher-
ited or genetically defined leukodystrophy, metabolic, or mito-
chondrial disease, systemic and laboratory features suggestive of
systemic lupus erythematosus or connective tissue disease, or
radiation- or chemotherapy-associated white matter damage. Ex-
clusion was determined by the reporting physician.
Statistical analyses. Descriptive statistics summarize clinical
and demographic data. Comparisons across clinical presenta-
tions (categorized as ADEM, mono-ADS [which included TM,
ON, and mono-ADS other], and poly-ADS) with respect to age
(younger than 10 years and older than 10 years) were performed
using ␹2 tests. This method also assessed the influence of sex and
of season among the most common clinical presentations:
ADEM, ON, and TM. Annual ADS incidence rates were calcu-
lated using Statistics Canada’s 2006 Census data19 and were
compared using Poisson regression. Logistic regression, using a
backward elimination selection procedure with a significance
level for removal of 0.10, explored potential predictors (sex, age,
clinical presentation, MRI evidence of white matter lesions) of
reporting physicians’ decisions to prescribe treatment for the
ADS event.
RESULTS Prestudy questionnaire. Of the 2,445 pe-
diatric health care providers, 611 (25%) completed
and returned the questionnaire. Of these 611, 21%
(130 physicians) reported having seen one or more
children with CNS demyelination within the 2 years
Neurology 72 January 20, 2009 233

Table Demographic characteristics
Age at demyelination, mean ⴞ SD (range), y
Age as a function of clinical presentation,
mean ⴞ SD (range), y
returned (n ⫽ 10), or the child already met criteria
for pediatric MS (n ⫽ 17). Clinical and demographic
10.5 ⴞ 4.6 (0.66 –17.96) data were analyzed for 219 children with confirmed
ADS (table).

ADEM (n ⴝ 49) 7.7 ⴞ 4.4 (0.9 –16.26) Incidence. The incidence of ADS in Canadian chil-
Monolesional ADS dren was calculated using national and provincial
TM (n ⴝ 49) 11.01 ⴞ 5.1 (0.66 –17.35) population data19 (figure 1). The annual average inci-
ON (n ⴝ 51) 11.5 ⴞ 3.2 (3.19 –16.94) dence was 0.9 per 100,000 Canadian children (95%
Mono-ADS other (n ⴝ 24) 11.7 ⴞ 4.7 (1–17.91) confidence interval [CI] 0.8 –1.1/100,000) (year 1:
Polylesional ADS 0.9/100,000 Canadian children [95% CI 0.7–1.1/
Poly-ADS (n ⴝ 35) 11.4 ⴞ 4.6 (2.17–17.96)
100,000]; year 2: 1.0/100,000 [95% CI 0.9 –1.3/
Both TM and ON (n ⴝ 8) 11.3 ⴞ 4.5 (4.81–17.5)
100,000]; year 3: 0.8/100,000 [95% CI 0.6 –
Sex, F:M 1.09:1.00
1.0/100,000]; p ⫽ 0.20). The lower rates in Quebec
Child’s country of birth, n (%)
(0.6/100,000, 95% CI 0.3–1.1/100,000) and
Canada 193 (88)
Saskatchewan (0.6/100,000, 95% CI 0.04 –2.4/
Other 17 (8)
100,000) and higher rate in Manitoba (1.6/100,000,
Not indicated 9 (4)
95% CI 0.5–3.7/100,000) were not significantly
Parents’ country of birth, n (%) Mother Father

Canada 125 (57) 132 (62)

different. In Manitoba, one regional pediatric
Other 71 (32) 66 (30)
health center serves the majority of the children in
Unknown 5 (2) 5 (2) the province. This center was actively involved in
Not indicated 18 (8) 6 (7) our national prospective study of demyelination,
Ethnicity, n (%) ADEM (n ⴝ 49) ON (n ⴝ 51) TM (n ⴝ 49) increasing the likelihood of case ascertainment. In
European 33 (68) 29 (56) 30 (61) addition to ascertainment issues, it is possible that
Asian 6 (12) 5 (10) 5 (11)
unidentified clinical, demographic, or environ-
African 1 (2) 0 (0) 0 (0)
mental factors may have influenced the higher rate
in Manitoba and lower rates in Quebec and
Middle Eastern 1 (2) 1 (2) 1 (2)
Saskatchewan; further studies are required to ad-
Caribbean 1 (2) 1 (2) 1 (2)
dress this point. No children with ADS were iden-
South American 0 (0) 5 (10) 2 (4)
tified in Prince Edward Island, Yukon, Northwest
Aboriginal 0 (0) 2 (4) 3 (6)
Territories, or Nunavut, likely because of the low
Mixed 2 (4) 6 (12) 4 (8)
pediatric population of these regions (34,214 resi-
Not provided 5 (10) 2 (4) 3 (6)
dent children in PEI, 13,563 in the Yukon,
Family history of autoimmune disease, n (%) 13,606 in the Northwest Territories, and 8,026 in
Multiple sclerosis 17 (8) Nunavut). The three most common clinical ADS
Juvenile diabetes 9 (4) presentations had similar incidence rates (ADEM:
Systemic lupus erythematosus 4 (2) 0.2/100,000 Canadian children [95% CI 0.15–
Thyroiditis 9 (4) 0.3/100,000]; TM: 0.2/100,000 [95% CI 0.15–
0.3/100,000]; ON: 0.2/100,000 [95% CI 0.16 –
ADEM ⫽ acute disseminated encephalomyelitis; mono-ADS ⫽ monolesional presentation;
0.3/100,000]).
TM ⫽ transverse myelitis; ON ⫽ optic neuritis; poly-ADS ⫽ polylesional presentation.

Demographic characteristics. The female:male ratio

preceding the prestudy questionnaire, and 85 physi-
cians stated that they had considered the diagnosis of
MS and had discussed this possibility with the child
and family.
Surveillance study. Initial reporting forms were re-
ceived from 2,005 of 2,445 health care providers
(82%) in year 1, 2,107 of 2,570 (82%) in year 2, and
2,033 of 2,606 (78%) in year 3. A total of 261 chil-
dren were reported. Of these, 42 were excluded be-
cause they did not meet the inclusion criteria or their
date of demyelination did not fall within the study
period (n ⫽ 15), detailed reporting forms were not
was 1.09:1. The sex ratio remained consistent when
evaluated as a function of age: 1.07:1 in children
younger than 10 years, and 1.10:1 in children aged
10 years or older. Figure 2 displays the frequency of
ADS as a function of age at presentation (median
11.1 years, range 0.5–18 years).
Although all children were Canadian residents,
8% were born outside of Canada and 37% were first-
generation Canadians (both parents born outside of
Canada). The relative representation of ethnicities
did not differ when evaluated as a function of the
more common ADS presentations (ADEM, ON, or
TM), and a family history of MS was reported in

234 Neurology 72 January 20, 2009

 Figure 1 Provincial incidence of acquired demyelinating syndromes in Canadian children (per 100,000;
averaged over the 3 year study)
P.E.I. ⫽ Prince Edward Island; Sask. ⫽ Saskatchewan.
8%, juvenile-onset type 1 diabetes in 4%, thyroiditis
in 4%, and systemic lupus in 2% (table).
Clinical presentations. The table describes the mean
age for each of the ADS presentations. Children with
ADEM were younger than children with other clini-
cal presentations (p ⬍ 0.0001). Figure 3 delineates
the relative frequency of ON, TM, ADEM, mono-
Figure 2 Distribution of acquired demyelinating syndromes (ADS) as a
function of age
ADS other, and poly-ADS for the entire cohort and
as a function of age at presentation (younger than 10
years, or aged 10 years and older). Children with
ADEM were more likely to present when younger than
10 years, whereas children experiencing monolesional-
ADS (including ON, TM and other) were more likely
to be older than 10 years (p ⬍ 0.001).
The female:male ratio was highest for children
with ON (1.43:1), whereas males were more likely to
present with TM (0.85:1) and ADEM (0.81:1), al-
though these relationships were not significant.
The incidence of the three most common clinical
presentations (ON, TM, ADEM) did not differ ac-
cording to season (ON: p ⫽ 0.46; TM: p ⫽ 0.88;
ADEM: p ⫽ 0.64) (figure 4). Nine children (4%)
received vaccinations within 1 month of ADS onset:
hepatitis B vaccine (n ⫽ 2), influenza vaccine (n ⫽
1), measles, mumps, and rubella vaccine (n ⫽ 1),
Gardasil (n ⫽ 1), pertussis vaccine (n ⫽ 1), Adacel (n
⫽ 1), unknown (n ⫽ 2).
Fever was reported in 49 of 217 children
(23%): 29 with ADEM, 3 with ON, 10 with TM,
and 7 with polylesional ADS. Seizures occurred in
15 of 217 children (7%): 10 with ADEM, 1 with
ON, 1 with TM, 2 with monolesional ADS other,
and 1 with polylesional ADS. Detailed reporting
forms for 2 patients did not indicate the presence
or absence of fever or seizures.
Neurology 72 January 20, 2009 235

Figure 3 Relative proportion of children with each of the ADS presentations
and representation of these ADS presentations as a function of
age younger or older than 10 years
ADEM ⫽ acute disseminated encephalomyelitis; TM ⫽ transverse myelitis; ON ⫽ optic neu-
ritis; ADS ⫽ acquired demyelinating syndromes; mono-ADS ⫽ monolesional presentation;
poly-ADS ⫽ polylesional presentation.
MRI was performed in 208 children (95%) and
was reported to be abnormal in 82% (n ⫽ 171).
MRI evidence of white matter lesions occurred in
more than 90% of children with demyelination re-
ferable to the brain but in only 40% of children with
clinically isolated ON. MRI was reported as abnor-
mal in 91% of children with TM, but the question-
naire did not specify whether this referred to MRI of
the spine only.
Treatment. Therapy was prescribed for more than
82% (180 children) at the time of their ADS presen-
tation. Of these, 92% received IV methylpred-
236 Neurology 72 January 20, 2009
nisolone and 62% received oral prednisone (likely as
an oral taper after IV therapy, although this was not
specified), 17% received IV immunoglobulin, and
8% received other therapies. The presence of abnor-
mal white matter on MRI was an important predic-
tor of reporting physicians’ decisions to prescribe
treatment for ADS (odds ratio [OR] ⫽ 2.23, p ⫽
0.07). Clinical presentation (OR ⫽ 1.0, p ⫽ 0.98),
age (OR ⫽ 0.8, p ⫽ 0.68), and sex (OR ⫽ 1.2, p ⫽
0.62) did not emerge as predictors of the likelihood
of treatment. Of the 33 children for whom cortico-
steroid therapy was not prescribed, 13 had ON, 4
had ADEM, 3 had TM, and 13 had mono-ADS (at
sites extrinsic to the optic nerves or spinal cord) or
poly-ADS. Data on clinical severity was not col-
lected, likely an important additional predictor of
physician decision to treat.
Discussion about risk of recurrent demyelination. Cli-
nicians discussed recurrent demyelination and the
potential for a future diagnosis of MS with 181 fam-
ilies (83% of all cases). When stratified by year of
study, discussion of MS risk occurred with 74% of
the families in study year 1, 85% in year 2, and 88%
in year 3.
DISCUSSION Acquired inflammatory demyelina-
tion of the CNS affects 0.9 per 100,000 Canadian
children per year, and there seems to be no seasonal
influence. Incidence rates were similar for the most
common clinical presentations, ADEM (0.2/
100,000 per year), ON (0.2/100,000 per year), and
TM (0.2/100,000 per year).
A family history of MS in first- or second-degree
relatives was reported by only 8% of the ADS pa-
tients. Although the frequency of familial MS in kin-
dreds of adults with an initial demyelinating event is
unknown, a family history of MS has been docu-
mented in 19.8% of 1,044 adult MS patients sur-
veyed from a Canadian MS clinic.20 Familial MS
rates in pediatric MS or ADS kindreds may be un-
derestimated because family members are young and
may still develop demyelination in the future. Fami-
lies of children with ADS also reported other autoim-
mune disease (juvenile diabetes, 4%; thyroiditis, 4%;
and systemic lupus erythematosus, 2%). A study of
familial autoimmunity in Canadian adult MS pa-
tients reported a lower rate of juvenile diabetes
(0.4%) but did not explore thyroiditis or lupus.21 A
study in the United Kingdom did not reveal any in-
crease in autoimmunity in MS families relative to
families of healthy controls.22 We are unaware of any
study exploring the frequency of autoimmune disease
in relatives of healthy Canadian children.
Of interest was the observation that 37% of chil-
dren with ADS were first-generation Canadians, a

Figure 4 Seasonal distribution of acute disseminated encephalomyelitis,
transverse myelitis, and optic neuritis
No specific seasonal effect is noted (ON: p ⫽ 0.46; TM: p ⫽ 0.88; ADEM: p ⫽ 0.64). ADS ⫽
acquired demyelinating syndromes; ADEM ⫽ acute disseminated encephalomyelitis; TM ⫽
transverse myelitis; ON ⫽ optic neuritis.
finding similar to our prior analysis of ethnicity in a
pediatric population from Toronto, Canada.23
Unlike studies of pediatric MS where the sex ratio
clearly demonstrates a female preponderance after
puberty,1,24 the sex ratio for ADS in children did not
change as a function of age. The absence of an age-
related female preponderance may relate to the vari-
able MS risk associated with different ADS
presentations. Male patients more commonly pre-
sented with ADEM and TM, clinical presentations
considered less likely to be the harbinger of MS (re-
viewed in reference 1).
Specific paraclinical features may be more predic-
tive of MS risk than demographic variables. In our
prior work, we reported that 68% of children with
ON, accompanied by MRI evidence of at least one
white matter lesion in the brain, will be diagnosed
with MS within 2 years.25 Other studies of ON in
children have reported subsequent MS diagnosis
rates between 26% and 56%, although MRI features
were variably reported.7,17 Of the 48 children with
ON in the current study, 40% were reported to have
an abnormal MRI and thus represent a subgroup
considered to be at particularly high risk for a future
diagnosis of MS.
Another important potential influence on clinical
presentation is age at ADS onset. Of the 219 chil-
dren, 95 were younger than 10 years. As expected, an
ADEM presentation was particularly prominent in
this age group (37%). Whether the polylesional fea-
tures, global impairment of alertness (encephalopa-
thy), and widespread MRI lesion pattern
characteristic of ADEM delineate a unique pathobi-
ology or an age-related propensity for heightened in-
flammation is an important area for future research.
Our survey did not directly evaluate the physical
or cognitive morbidity of ADS, and children with
mild ADS symptoms may be underreported. How-
ever, corticosteroid therapies were prescribed for
more than 80% of children, suggesting a relatively
high degree of clinical acuity. The impact of ADS on
the long-term health of Canadian children is the sub-
ject of ongoing research.
To date, incidence studies of ADS in children
have focused on ADEM or established MS.3,4 A
study in San Diego County, California, used retro-
spective and prospective data from three regional
centers, included persons younger than 20 years, and
defined ADEM as any acute first demyelinating event
associated with neuroimaging evidence of demyelina-
tion.4 The reported incidence of 0.4 per 100,000
may seem higher than the incidence of ADEM (0.2
per 100,000) in our study. However, applying their
definition for ADEM to our population (n ⫽ 171
children with ADS and abnormal MRI) would actu-
ally yield a higher incidence of 0.7 per 100,000 (al-
though we cannot comment on incidence in
Canadians aged 18 –20 years). The incidence of
ADEM reported in a national survey of German chil-
dren (younger than 16 years) was 0.07 per 100,000.3
Although we included children up to age 18 years,
we identified only two adolescents with ADEM be-
tween age 16 and 18 years. Thus, although our data
suggest that ADEM may be more common in Cana-
dian children, multinational collaborative studies
with unified methodologies are required to validate
this observation.
Our study is strengthened by standardized clinical
inclusion criteria and demographic collection forms.
Nonetheless, we acknowledge the limitations of
survey-based methodologies as response rate directly
influences estimated disease incidence. Given that
78% to 82% of surveyed physicians completed the
monthly forms, a response rate similar to other CPSP
initiatives,26 we believe that our data represent at least
an 80% estimate of the incidence of ADS in Cana-
dian children.
Important to our work was the education of pedi-
atric health care providers on the potential risk of
MS. The prestudy survey indicated that only 65%
had considered the possibility of MS in their pediat-
ric ADS patients. By study completion, more than
85% of reporting physicians stated that they had
considered MS as a possible outcome of ADS in chil-
dren. Although the increase in physician consider-
ation of MS risk may reflect the fact that the initial
survey queried physicians on prior care practices, and
Neurology 72 January 20, 2009 237
 the subsequent survey was posed to respondents ac-
tively engaged in the care of children with ADS, we
believe that the increase reflects the effectiveness of
the educational materials provided to clinicians dur-
ing the study.
Our national, 23-site, prospective, Canadian
study of ADS in children is now under way to define
MS risk, as well as the clinical, demographic, immu-
nologic, and neuroimaging features predictive of this
outcome.
AUTHORS’ AFFILIATIONS
From The Hospital for Sick Children (B.B., J.K., S.M.), Toronto, On-
tario; University of British Columbia (C.G., D.S.), Vancouver, British
Columbia; Vancouver Coastal Health Authority (C.G., D.S.), UBC Hos-
pital, British Columbia; Montreal Neurological Institute (D.L.A., A.B.-
O.), Quebec; McGill University (D.L.A., A.B.-O.), Montreal, Quebec;
Victoria General Hospital (K.W.), British Columbia; Children’s Hospital
of British Columbia (M.B.C.), Vancouver, British Columbia; Stollery
Children’s Hospital (J.Y.), Edmonton, Alberta; Alberta Children’s Hospi-
tal (J.K.M.), Calgary, Alberta; The Children’s Hospital of Winnipeg
(N.S.), Manitoba; Centre Hospitalier Universitaire de Sherbrooke (G.S.),
Quebec; McMaster Children’s Hospital (B.M.), Hamilton, Ontario; The
Montreal Children’s Hospital (M.-E.D.), Quebec; Centre Hospitalier
Universitaire de Sainte-Justine (A.L.), Montreal, Quebec; Children’s
Hospital of Eastern Ontario (S.W., A.D.), Ottawa, Ontario; Children’s
Hospital of Western Ontario (S.L.), London, Ontario; Queen’s Univer-
sity (E.A.M.), Kingston, Ontario; Saint John Regional Hospital (D.M.),
New Brunswick; IWK Health Centre (E.W.), Halifax, Nova Scotia; Royal
University Hospital (N.L.), Saskatoon, Saskatchewan; Janeway Children’s
Health and Rehabilitation Centre (D.B.), St. John’s, Newfoundland;
Trillium Health Centre (C.Y.), Mississauga, Ontario; Windsor Regional
Hospital (M.A.), Ontario; Rouge Valley–Centenary Hospital (P.C.),
Scarborough, Ontario; Hôpital Charles LeMoyne (F.G.), Montreal, Que-
bec; Sudbury Regional Hospital (J.B.B.), Ontario; and Dalhousie MS
Research Unit (V.B.), Halifax, Nova Scotia, Canada.
AUTHOR CONTRIBUTIONS
Statistical analyses were performed by S.M. and J.K.
ACKNOWLEDGMENT
The authors thank all of the Canadian pediatric health care providers
without whom this study could not have been performed. The authors
also thank all of the 23 site coordinators: Courtney Fairbrother, Shelia
Kent, Marjorie Berg, Catherine Riddell, Natarie Liu, Joan Kupchak,
Christian Houde, Fabiola Breault, Stephanie Pellerin, Heather Davies,
Heather Neuman, Laurie Wyllie, Chantal Horth, Mala Ramu, Edythe
Smith, Alison Crowell, Doris Newmeyer, Vee McBride, Sharon J. Pen-
ney, Leanne Montgomery, Loris Aro, Julie Lafrenière, Louise Roberts,
Laurie Robson, Trudy Campbell, Lucy Sagar, and Nancy Cacciotti; as
well as Jennifer Hamilton and Melissa McGowan for their invaluable
assistance.
Received May 12, 2008. Accepted in final form October 13, 2008.
REFERENCES
1. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M.
Multiple sclerosis in children: clinical diagnosis, therapeu-
tic strategies, and future directions. Lancet Neurol 2007;6:
887–902.
2. Krupp L, Banwell B, Tenembaum S; for the International
Pediatric MS Study Group. Consensus definitions pro-
posed for pediatric multiple sclerosis. Neurology 2007;68:
S7–S12.
3. Pohl D, Hennemuth I, von Kries R, Hanefeld F. Paediat-
ric multiple sclerosis and acute disseminated encephalomy-
238 Neurology 72 January 20, 2009
elitis in Germany: results of a nationwide survey. Eur
J Pediatr 2007;166:405–412.
4. Leake JA, Albani S, Kao AS, et al. Acute disseminated en-
cephalomyelitis in childhood: epidemiologic, clinical and
laboratory features. Pediatr Infect Dis J 2004;23:756–764.
5. Pidcock FS, Krishnan C, Crawford TO, Salorio CF, Tro-
vato M, Kerr DA. Acute transverse myelitis in childhood:
center-based analysis of 47 cases. Neurology 2007;68:
1474–1480.
6. Brown VE, Pilkington CA, Feldman BM, Davidson JE.
An international consensus survey of the diagnostic criteria
for juvenile dermatomyositis (JDM). Rheumatology (Ox-
ford) 2006;45:990–993.
7. Riikonen R, Donner M, Erkkila H. Optic neuritis in chil-
dren and its relationship to multiple sclerosis: a clinical
study of 21 children. Dev Med Child Neurol 1988;30:
349–359.
8. Mikaeloff Y, Adamsbaum C, Husson B, et al. MRI prog-
nostic factors for relapse after acute CNS inflammatory
demyelination in childhood. Brain 2004;127(pt 9):1942–
1947.
9. Banwell BL. Pediatric multiple sclerosis. Curr Neurol
Neurosci Rep 2004;4:245–252.
10. Mikaeloff Y, Suissa S, Vallee L, et al. First episode of acute
CNS inflammatory demyelination in childhood: prognos-
tic factors for multiple sclerosis and disability. J Pediatr
2004;144:246–252.
11. Keene DL, Sutcliffe T, Harman P, Grenier D. Surveillance
for progressive intellectual and neurological deterioration
in the Canadian paediatric population. Can J Neurol Sci
2004;31:220–224.
12. Campbell C, Levin S, Humphreys P, Walop W, Brannan
R. Subacute sclerosing panencephalitis: results of the Ca-
nadian Paediatric Surveillance Program and review of the
literature. BMC Pediatr 2005;5:47.
13. Canadian Pediatric Society. Surveillance: CPSP Studies.
Canadian Paediatric Surveillance Program. Ottawa, On-
tario; 2008.
14. Banwell B. Surveillance studies in 2006: acquired demyeli-
nating syndromes of the central nervous system. Canadian
Paediatric Surveillance Program 2006 Results. Ottawa,
Ontario; 2007:15–17.
15. Banwell B. Surveillance studies in 2005: acquired demyeli-
nating syndromes of the central nervous system. Canadian
Paediatric Surveillance Program 2005 Results. Ottawa,
Ontario; 2006:15–17.
16. Banwell B. Surveillance studies in 2004: acquired demyeli-
nating syndromes of the central nervous system. Canadian
Paediatric Surveillance Program 2004 Results. Ottawa,
Ontario; 2005:15–17.
17. Lucchinetti CF, Kiers L, O’Duffy A, et al. Risk factors for
developing multiple sclerosis after childhood optic neuri-
tis. Neurology 1997;49:1413–1418.
18. Transverse Myelitis Consortium Working Group. Myelitis
Consortium Working Group. Proposed diagnostic criteria
and nosology of acute transverse myelitis. Neurology
2002;59:499–505.
19. Government of Canada. Statistics Canada. www.statcan.
com. 2008.
20. Ebers GC, Koopman WJ, Hader W, et al. The natural
history of multiple sclerosis: a geographically based study,
8 —familial multiple sclerosis. Brain 2000;123(pt 3):641–
649.
 21. Ramagopalan SV, Dyment DA, Valdar W, et al. Autoim-
mune disease in families with multiple sclerosis: a population-
based study. Lancet Neurol 2007;6:604–610.
22. Broadley SA, Deans J, Sawcer SJ, Clayton D, Compston
DA. Autoimmune disease in first-degree relatives of pa-
tients with multiple sclerosis: a UK survey. Brain 2000;
123(pt 6):1102–1111.
23. Kennedy J, O’Connor P, Sadovnick AD, Perara M, Yee
I, Banwell B. Age at onset of multiple sclerosis may be
influenced by place of residence during childhood
rather than ancestry. Neuroepidemiology 2006;26:162–
167.
24. Ghezzi A, Deplano V, Faroni J, et al. Multiple sclerosis in child-
hood: clinical features of 149 cases. Mult Scler 1997;3:43–46.
25. Wilejto M, Shroff M, Buncic JR, Kennedy J, Goia C, Ban-
well B. The clinical features, MRI findings, and outcome of
optic neuritis in children. Neurology 2006;67:258–262.
26. Health Canada. Evaluation of the Canadian Paediatric
Surveillance Program. Canada Communicable Disease Re-
port 30S2. Ottawa, Ontario; 2004.

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REFERENCES
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2. Gronseth G, French J. Practice parameters and technology assessments: what they are, what they are not, and why you should care. Neurology
2008;71:1639 –1643.
3. Gross RA, Johnston KC. Levels of evidence: taking Neurology® to the next level. Neurology 2008;72:8 –10.

Neurology 72 January 20, 2009 239

 Incidence of acquired demyelination of the CNS in Canadian children
B. Banwell, J. Kennedy, D. Sadovnick, et al.
Neurology 2009;72;232-239
DOI 10.1212/01.wnl.0000339482.84392.bd

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