Intrathecal baclofen use in children with spasticity – a physicians' survey
infrequent by 24%. Mechanical and infection events werereported in the following frequencies: rare 41.5%, infrequent41.5%, common or very common 17%. Baclofen withdrawalevents were rare in 65%, infrequent in 27%, and common in 8%
‘Intrathecal baclofen use in children with spasticity – a physi-
of respondents’ experience. No difference in reported compli-
cations was found on the basis of experience or activity (num-
SIR–The use of intrathecal baclofen (ITB) during the past two
ber of pumps inserted and managed per year).
decades has resulted in major advances in the management of
Those surveyed were asked about what rates they may antic-
complex spasticity.1 There is increasing use of ITB in children
ipate of life and non-life threatening complications in children
for managing spasticity in a number of conditions, with evi-
of GMFCS Levels III, IV, or V. Respondents indicated that they
dence for effect across a range of functional domains.2
would tolerate the highest rate of both life and non-life threat-
However, significant complications have been reported.3,4
ening events in the most severely impaired children (GMFCS
These can be broadly divided into three groups: (1) mechani-
Level V) compared with those less impaired (p<0.005). When
cal; (2) central nervous system effects from dose excess or with-
asked whether they believed that the overall safety of ITB had
drawal; and (3) infections. In conducting a multicentre survey,
been adequately established in terms of the current evidence,
our primary aim was to describe the experience of individual
almost equal numbers replied yes (43%) and no (44%) and a
physicians with ITB management in children, specifically with
small number (13%) did not know. An overwhelming majority
regard to extent of use and complications noted.
(96%) of respondents indicated that an international database
A survey was conducted of physicians working with chil-
for ITB-related safety and complication issues would be essen-
dren with physical disabilities. This was mailed to 165 physi-
tial or useful. No difference was seen in terms of responses to
cians randomly selected from the membership register of the
section 4 between ITB users and non-users.
American Academy for Cerebral Palsy and Developmental
To our knowledge, this is the first survey on the use of
Medicine, and to an additional 35 physicians identified as
intrathecal baclofen specifically in children. We deliberately
ITB users on the basis of articles authored in the literature.
chose to explore the complications issue in this survey as there
The questionnaire asked for single choice responses and
is little known about this from a systematic perspective. Cur-
requested information in four key areas: (1) demographics;
rently there are no universally agreed guidelines on the opti-
(2) patient selection factors; (3) frequency of actual compli-
mal selection and management of children with ITB. The
cations; and (4) beliefs about potential complications and
responses on selection factors indicate that there is a large
access to safety data. Those physicians not currently involved
degree of variability in the decision-making process. One-third
with ITB were asked only to fill out section (4).
of respondents indicated that ITB withdrawal events occur in
Eighty-five physicians (43%) completed the survey; 69% of
more than 5% of recipients. ITB withdrawal can be difficult to
the overall sample was involved in the use of ITB. Of the ITB
diagnose, may be life-threatening, and, importantly, is largely
users, 40% had between 2 and 5 years’ experience and 44% had
preventable.6 To our knowledge, there has been no reporting
more than 5 years’ experience. Seventy-six per cent of respon-
on ITB withdrawal in children other than by case report.7–9
dents were working in centers where up to 50 implanted
We asked all respondents, regardless of their current use of
pumps were managed in the previous year. In describing their
ITB, what they believed to be acceptable cut-off rates for com-
role in the phases of management, 91% responded that they
plications in children of varying motor severity based on
were involved in preoperative assessment of the child’s suit-
GMFCS. Our hypothesis was that more physicians would con-
ability for the device. Nineteen per cent were involved in the
sider accepting higher complication rates in the more severely
operative implantation and 73% in the ongoing care of recipi-
impaired child, possibly as the need for benefit from ITB in a
more motorically impaired child is greater than for a less
When asked about a single minimum age criterion in iden-
impaired child. The results indicate that most physicians
tifying suitable candidates, 24% indicated that the child should
would accept higher rates of both life and non-life-threatening
be older than 5 years, 32% indicated older than 1 year, and
complication in GMFCS Level V children compared with Level
39% believed that a minimum age was not relevant to the
III or IV (p<0.005). This finding is challenging: are quality of
selection process. With respect to the child’s weight, 37%
life issues more important than safety issues to some physicians
believed a minimum of 10kg was acceptable and 46% indicat-
and families in deciding whether or not to choose ITB?
ed a minimum weight of 20kg. Respondents were also asked
While most physicians had access to information on com-
to indicate what degree of motor impairment would describe
plications in ITB, responses were split on whether respon-
a suitability for ITB on the basis of the descriptions of gross
dents believed that ITB is a safe procedure. Does this suggest
motor ability from the Gross Motor Function Classification
that broader concerns exist as to ITB as a procedure, or that
System (GMFCS)5 for Levels III, IV, and V. Forty-two per cent of
physicians need more information on which to make an
respondents would consider a child who ambulated with
informed judgment? Beyond data obtained from reports
assistive mobility devices (Level III) for ITB. Sixty-seven per
published in peer-reviewed journals, a single manufacturer
cent would consider a child with very limited ambulatory
of ITB pumps collects information from centres using ITB. In
skills who relied more on power mobility (Level IV), and 91%
the face of limited free availability through journals, the
would consider a non-ambulatory child (Level V).
question of whether a third party should collect and dissemi-
In order to improve recall and facilitate analysis the frequen-
nate safety-related information on ITB, in the form of an
cy of events were grouped in the following manner: rare (<5%
international registry, is an important issue. This would cre-
of recipients); infrequent (5–15%); common (16–25%); very
ate a more transparent reporting and access system for ITB
common (>25%). Dose-related events in the postimplanta-
safety information and could allow greater use of data in
tion period were reported as rare by 75% of respondents and
determining optimal and at-risk candidates. The need for
Developmental Medicine & Child Neurology 2006, 48: 1006–1011
greater access to education and strategies on pump problem
menarche since this is a very salient event, and can be recalled
accurately many years later. Data were available for 38 womenwith an ASC, diagnosed by psychiatrists using InternationalClassification of Diseases-10th revision3 criteria. Their meanage was 31 years 6 months (SD 9y 10mo; range 18y 11mo–57y
9mo). Specific diagnoses were available for 35 of the women.
Ten were diagnosed with autism, two with high functioning
autism, and 23 with Asperger syndrome. Several also hadcomorbid diagnoses including severe learning disability,*
aPaediatric Rehabilitation Service, The Royal Children’s
Tourette syndrome, attention-deficit disorder, dyslexia, dys-
praxia, epilepsy, depression, and anxiety. They were recruited
bDivision of Developmental Paediatrics, University of British
via the National Autistic Society (UK), specialist clinics, and
adverts in relevant newsletters/web-pages. Data from an age-matched comparison group of 38 females without ASC were
*Correspondence to: firstname.lastname@example.org
also collected (mean age 32y 2mo [SD 9y 1mo]; range 19y–36y5mo). This was not significantly different from the group withASC, t(74)=–0.10, p=0.92, d=0.07. All women were asked the
References1. Penn RD, Kroin JS. (1984) Intrathecal baclofen alleviates spinal
following question: ‘How old were you when you had your first
cord spasticity. Lancet 1: 1078. (Letter)
period?’. They were asked to indicate age in years and months.
2. Butler C, Campbell S. (2000) Evidence for the effects of
They were also asked ‘What date was it (month/year)?’ If partic-
intrathecal baclofen for spasticity and dystonic cerebral palsy.
ipants answered both questions, recalled age was used in the
Dev Med Child Neurol 42: 634–645.
subsequent analysis as this is remembered more accurately. In
3. Murphy NA, Nicole Irwin MC, Hoff C. (2002) Intrathecal baclofen
therapy in children with cerebral palsy: efficacy and
four women with classical autism the participant’s mother
complications. Arch Phys Med Rehabil 83: 1721–1725.
responded; analyses were run with and without these cases.
4. Gooch JL, Oberg WA, Grams B, Ward LA, Walker ML. (2003)
Participants were excluded if they reported having a hormonal
Complications of intrathecal baclofen in children. Pediatr
condition that could influence the variable being tested, such
5. Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B.
as thyroid gland abnormalities, diabetes, and anorexia. Three
(1997) Development and reliability of a system to classify gross
women were removed from the ASC group for exclusionary
motor function in children with cerebral palsy. Dev Med Child
conditions. Because timing of menarche differs among ethnic
groups,1 only participants with a Caucasian background were
6. Coffey RJ, Edgar TS, Francisco GE, Graziani V, Meythaler JM,
included in this study. The reported study was approved by the
Ridgely PM, Sadiq SA, Turner MS. (2002) Abrupt withdrawal fromintrathecal baclofen: recognition and management of a potentially
Cambridge Psychology Ethics Comittee. Informed consent was
life-threatening syndrome. Arch Phys Med Rehabil 83: 735–741.
7. Alden TD, Lytle RA, Park TS, Noetzel MJ, Ojemann JG. (2002)
Three of the women in the ASC group had their first period
Intrathecal baclofen withdrawal: a case report and review of the
at a very late age (20y 3mo, 20y 1mo, and 20y). One woman in
literature. Childs Nerv Syst 18: 522–525.
8. Samson-Fang L, Gooch J, Norlin C. (2000) Intrathecal baclofen
the control group had a delayed age at menarche (17y 8mo).
withdrawal simulating neuroleptic malignant syndrome in a
This represents a significant minority of the women with ASC.
child with cerebral palsy. Dev Med Child Neurol 42: 561–565.
Even excluding these women, a t-test showed that women
9. Dawes WJ, Drake JM, Fehlings D. (2003) Microfracture of a
with ASC, on average, began their periods at a later age than
baclofen pump catheter with intermittent under- and overdose.
the women in the control group (13y 4mo vs 12y 7mo respec-
10. Yeh RN, Nypaver MM, Deegan TJ, Ayyangar R. (2004) Baclofen
tively), t(69)=1.95, p=0.055, d=0.45. Levene’s test4 indicated
toxicity in an 8-year-old with an intrathecal baclofen pump.
equal variance. The probability of a type I error was main-
tained at 0.05. A significant difference was also found whenparticipants whose mother’s responded were excluded, (13y6mo vs 12y 7mo), t(67)=1.95, p=0.02, d=0.60. The cause ofthis delay remains open to investigation.
‘Age of menarche in females with autism spectrum conditions’
One possibility is the influence of prenatal androgen. It
SIR–Studies in typical populations show that the timing of
has recently been suggested that high testosterone may be a
pubertal development has important behavioural and psy-
risk factor for autism.5 Our results are compatible with this
chosocial consequences.1 In children with autism spectrum
theory in that female rhesus monkeys exposed to high levels
conditions (ASC), puberty may produce changes in symptoms.
of androgens early in gestation experience delayed menar-
Some studies report that between one-tenth and one-third of
che.6 Females with ASC show other markers of high testos-
children with ASC experience deterioration and aggravation of
terone including a low 2nd to 4th digit ratio, potential
symptoms soon after entering puberty; this may be particularly
somatic hypermasculinization,5 and a more masculine pat-
the case for females.2 Given the potential impact of the puber-
tern of play (Knickmeyer et al. unpublished).
tal transition on symptom severity and the possibility that
Another major candidate is body mass index (BMI).
females with ASC share some of the same vulnerabilities that
Females who are obese tend to enter puberty at an earlier age
arise from early or delayed maturation in the general popula-
than their peers, while strict training in activities such as
tion, a better understanding of puberty timing in these individ-
sports or ballet dancing delays menarche.1 Children with
autism often have dietary abnormalities which could affect
In this letter, we report the results of a cross-sectional sur-
vey of age at menarche in women with ASC. We focused on
North American usage: mental retardation.
their BMI. Stress is also thought to affect menarche, but due to
6. Abbott DH, Dumesic DA, Eisner JR, Kemnitz JW, Goy R. (1997)
the highly subjective nature of this phenomenon, it is difficult
The prenatally androgenized female rhesus monkey as a model
to study. Given that our study included no clinical controls, our
for PCOS. In: Azziz R, Nestler JE, Dewailly D, editors. AndrogenExcess Disorders in Women. Philadelphia: Lippincott–Raven.
results could reflect stress associated with having a clinical con-
dition. Females with cerebral palsy and females with severe
7. Evans AL, McKinlay IA. (1988) Sexual maturation in girls with
cognitive impairment may also have delayed puberty.7,8 How-
severe mental handicap. Child Care Health Dev 14: 59–69.
ever, females with Down syndrome experience menarche at an
8. Worley G, Houlihan CM, Herman-Giddens ME, O’Donnell ME,
Conaway M, Stallings VA, Chumlea WC, Henderson RC, Fung EB,
earlier age than the general population. Age of menarche
Rosenbaum PL, et al. (2002) Secondary sexual characteristics in
shows no deviation in fragile X syndrome.9 The factors produc-
children with cerebral palsy and moderate to severe motor
ing this variation across conditions merit further study, but may
impairment: a cross-sectional survey. Pediatrics 110: 897–902.
include activity level (acting through BMI) as well as physiologi-
9. Burgess B, Partington M, Turner G, Robinson H. (1996) Normal
cal factors specific to the conditions. Individuals with clinical
age of menarche in fragile X syndrome. Am J Med Genet 64: 376.
conditions may have taken medications which alter their meta-bolic or endocrine status, thereby affecting timing of menarche.
In conclusion we found a significant minority of women
‘Ferritin as an indicator of suspected iron deficiency in chil-
with autism have an extremely late onset of menarche. We have
dren with autism spectrum disorder: prevalence of low serum
since been contacted by another woman with autism who, at
the age of 26, has never experienced menarche. Even exclud-
SIR–Children with autism spectrum disorder (ASD) often have
ing these extreme cases, menarche was delayed in women with
limited iron intake1 as shown by Latif et al.2 who found children
ASC compared with age-matched controls by 8 months. Whilst
with ASD to have a high prevalence of low serum ferritin levels,
intriguing, our findings are limited in that they included only a
a widely-used screening test for depleted iron stores.2–4 The
single ethnic group and relied on participants recalling their
cut-off values used for low ferritin differ across centers (<6ug/L
age at menarche and self-reporting exclusionary clinical condi-
to <22ug/L25–8), limiting its accuracy for detecting the pres-
tions; the study was also of a relatively small sample size. A com-
ence of iron deficiency. The World Health Organization9
prehensive study of pubertal development, which takes
reports a geometric mean of normal ferritin levels of 34ug/L
account of nutritional status, medication, and other variables
whilst Milman et al.7 reported a mean of 38.5ug/L. The
relevant to pubertal development in women with ASC, is need-
American Association for Clinical Chemistry uses a range of 6 to
ed before any strong conclusions can be drawn. Our results
24ug/L (1–5y) and 10 to 55ug/L (6–9y).6 The National Health
suggest that such a study would be worthwhile.
and Nutrition Examination Survey (NHANES)5 chose the fer-ritin level cut-off that fell near the fifth centile for age.
In this retrospective chart review, all 96 children (78
males, 18 females) who had undergone an ASD diagnostic
assessment at the tertiary level Child Development Centre
(1998–2003), located in The Hospital For Sick Children,
Toronto, Canada, were included, regardless of their nutri-
tional history. In our center’s population of children withASD, although the ferritin level was initially measured only in
aDepartment of Psychiatry, University of North Carolina-
those whose nutritional history suggested risk for iron defi-
Chapel Hill, Neurosciences Hospital, Chapel Hill, NC, USA.
ciency, the frequent finding of low ferritin levels led to the
bThe Autism Research Centre, Departments of Experimental
clinical practice of routine measurement of serum ferritin
Psychology and Psychiatry, University of Cambridge,
concentration in 1998 during all diagnostic assessments of
children with ASD in order to screen more formally for iron
cDepartment of Biological Psychology, Vrije Universiteit,
deficiency. In the current study, ferritin levels were recorded
and mean corpuscular volume (MCV; <80fL10) and haemo-globin (Hb; <110g/L in 2–4-year-olds and <120g/L in 5–10-year-
*Correspondence to: email@example.com
olds10) were used as measures of iron deficient erythropoei-sis because ferritin by itself does not indicate the severity of
iron deficiency once iron stores are fully depleted.11 To com-
1. Weichold K, Silbereisen K, Schmitt-Rodermund E. (2003) Short-
pare the prevalence of low ferritin in children with ASD to
term and long-term consequences of early versus late physical
that of iron deficiency in the general population, we used the
maturation in adolescents. In: Hayward C, editor. Gender
same cut-off values as those described in the Center for
Differences at Puberty. Cambridge: Cambridge University Press. p 241–276.
Disease Control and Prevention (CDC) recommendations to
2. Gillberg C. (1984) Autistic children growing up: problems during
prevent and control iron deficiency.3,12 Their data were drawn
puberty and adolescence. Dev Med Child Neurol 26: 122–129.
from NHANES,5 using a cut-off of <10ug/L for preschool chil-
3. World Health Organization. (1994) International Classification
dren (age 1–5y) and <12ug/L for school-aged children (6y and
of Diseases, 10th edn. (ICD-10) Geneva, Switzerland: WorldHealth Organization.
older). A weakness of our design was the lack of multiple mark-
4. Levene H. (1960) Robust tests for equality of variances. In: Olkin I,
ers available for iron deficiency; these could have been benefi-
Ghurye S, Hoeffding W, Madow W, Mann H, editors. Contributions
cial because ferritin lacks a uniform reference range in the
to Probability and Statistics: Essays in Honor of Harold Hotelling.
literature and ferritin can become falsely elevated by physiolog-
Stanford, CA: Stanford University Press. p 278–292.
ical fluctuations.11,13 χ2 test or Fisher’s exact test were used to
5. Baron-Cohen S, Knickmeyer RC, Belmonte MK. (2005) Sex
differences in the brain: implications for explaining autism.
test the difference between two proportions, two-indepen-
dent sample t-tests or Mann–Whitney U tests were used to test
Developmental Medicine & Child Neurology 2006, 48: 1006–1011
differences in means between two samples, and Pearson’s cor-
3. Centers for Disease Control and Prevention, US Department of
Health and Human Services. (1998) Recommendations to prevent
relation was used for patterns of association between continu-
and control iron deficiency in the United States. MMWR
The mean age of the 61 preschoolers (1–5y) and 35 school-
4. Borch-Iohnsen B. (1995) Determination of iron status: Brief review
aged children (6–10y) was 5 years 5 months. Median ferritin
of physiological effects on iron measures. Analyst 120: 891–893.
5. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. (1997)
was 17.1ug/L (range 2.5ug/L–49.2ug/L). Two preschool chil-
Prevalence of iron deficiency in the United States. JAMA
dren had an outlying ferritin level (168.4ug/L and 175.5ug/L).
Ferritin did not appear to differ with age (preschool children
6. Soldin SJ, Brugnara C, Hicks JM. (1999) Pediatric Reference Ranges,
[17.2ug/L], school-aged children [16.6ug/L]; p=0.61).
3rd edn. Washington, DC: American Association for Clinical
Ferritin was low in 1/12 of 1–2-year-olds with ASD, similar to
7. Milman N, Backer V, Laursen EM, Graudal N, Ibsen KK, Jordal R.
the 7% prevalence of iron deficiency reported in the general
(1994) Serum ferritin in children and adolescents. Results from
population at that age;5,12 it was also low in 7/49 of 3–5-year-
population surveys 1979 and 1986 comprising 1312 individuals.
olds, more than double the 5% typical prevalence,5,12 and in
7/35 of 6–10-year-olds, fivefold greater than the 4% typical
8. Murthy JN, Hicks JM, Soldin SJ. (1995) Evaluation of the technicon
immuno I random access immunoassay analyzer and calculation of
prevalence.5,12 MCV was low in 48% (44/91), associated with
pediatric reference ranges for endocrine tests, T-uptake, and
median ferritin 17.4ug/L; Hb was low in 19% (17/91). A ferritin
ferritin. Clin Biochem 28: 181–185.
level above 12ug/L was present in 34/43 of those children with
9. DeMaeyer EM. (1989) Preventing and Controlling Iron Deficiency
low MCV and in 16/17 of those with low Hb. Lower ferritin val-
Anaemia through Primary Health Care – A Guide for Health
ues were correlated with higher ADOS14 communication
Administrators and Programme Managers. Geneva, Switzerland:World Health Organization. p 7–38.
scores (p=0.005), indicative of more severely impaired com-
10. Lewis SM, Dacie JV, Bain BJ, Bates I. (1991) Dacie and Lewis
munication, which could reflect more restricted diets in
Practical Haematology, 7th edn. Oxford: Churchill Livingstone.
impaired children, or that behavioural difficulties are exacer-
11. Cook JD, Baynes RD, Skikne BS. (1992) Iron deficiency and the
measurement of iron status. Nutr Res Rev 5: 189–202.
Assuming low ferritin indicates iron deficiency in this popu-
12. Centers for Disease Control and Prevention. (2002) US
lation, this study confirmed a much higher prevalence of iron
Department of Health and Human Services. Iron Deficiency-
deficiency in children with ASD than in the general population.
United States, 1999–2000. MMWR 51: 897–899.
This may be associated with more severe ASD impairment. The
13. Madanat F, El-Khateeb M, Tarawaneh M, Hijazi S. (1984) Serum
high rate of microcytosis supports the presence of iron defi-
ferritin in evaluation of iron status in children. Acta Haematol71: 111–115.
ciency, but its associated high prevalence of ferritin above cut-
14. Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC,
off values suggests that ferritin measurements may miss some
Pickles A, Rutter M. (2000) The autism diagnostic observation
children with iron deficiency and supports the need for multi-
schedule-generic: a standard measure of social and
ple markers.13 In conclusion, children with ASD represent a
communication deficits associated with the spectrum of autism. J Autism Dev Disord 30: 205–223.
high risk group for iron deficiency, and need close monitoring,even at school-age, in accordance with the CDC3 recommenda-tion to screen populations at risk for iron deficiency.
‘Interobserver reliability of visual interpretation of electro-
encephalograms in children with newly diagnosed seizures’
SIR–Stroink and colleagues recently addressed the important
question of interobserver reliability in electroencephalograms
(EEGs) of children with newly diagnosed seizures and con-
cluded that ‘the reliability of the visual interpretation of EEGs
in children is almost perfect as regards the presence of epilepti-
form abnormalities’.1 The methods of this study should make
us skeptical of the generalizability of this conclusion.
First, their case mix differs from the typical clinical case mix.
The authors selected two groups of EEGs from their first
aGlenrose Rehabilitation Hospital, University of Alberta,
seizure/newly diagnosed epilepsy study. In the first group, 56
of 72 (78%) had been read by the first EEG reader as abnormal. bDepartment of Psychology, York University;
In the second, 37 of 39 were interpreted abnormal. In standard
cChild Development Centre, The Hospital For Sick Children,
clinical practice, EEGs are ordered in a much more diverse mix
University of Toronto, Toronto, Ontario;
of patients. Even in comparable first seizure or epilepsy
dDepartment of Public Health Sciences, University of
patients, the proportion of EEGs that will show abnormalities
Alberta, Edmonton, Alberta, Canada.
is far lower. So, conclusions drawn on the basis of this case mixmay not be generalizable to all situations where EEGs are per-formed in children. *Correspondence to: firstname.lastname@example.org
Second, these authors are experienced clinical neurophysi-
ologists who have been collaborating in epilepsy research for
years. Thus, one would expect them to have worked to reduce
1. Cornish E. (1998) A balanced approach towards healthy eating in
interobserver variation, and that over time a convergence in
autism. J Hum Nutr Diet 11: 501–509.
2. Latif A, Heinz P, Cook R. (2002) Iron deficiency in autism and
EEG interpretation would occur. This may partly explain the
Asperger syndrome. Autism 6: 103–114.
high level of agreement. However, there is no reason to think
that neurologists trained at a wide variety of institutions for
the prognostic value of EEGs in studies of children with
varying periods of time would currently achieve this high level
epilepsy or a first seizure.2 Gilbert et al. concluded that a
large variation exists in the conditions of children referred
In fact, evidence from other large studies shows that inter-
for EEG and a large interreader variation because of diverg-
observer reliability is much lower than the authors report. If
ing specificity and sensitivity of the EEG between studies. We
the reliability of EEG reading is ‘almost perfect’ in children, one
investigated the interrater reliability of the EEG in children
would expect that the test characteristics of EEGs would be
diagnosed with epilepsy by experienced paediatric neurolo-
highly consistent across studies in children. However, our
gists. We think that our results do not conflict but agree with
meta-analysis of studies involving over 2000 children showed
most of the findings of Gilbert et al.1,2
sensitivity ranged from 33 to 91% and specificity from 13 to
A seizure and epilepsy need to be diagnosed on the basis
80%. Moreover, the readers’ interpretation threshold varied,
of the history of the events and, if available, on (home)
and this significantly influenced the predictive accuracy of EEG
videos. EEG may support the diagnosis of epilepsy only if the
for seizure recurrence.2 In the community setting, we found, in
clinical suspicion of epileptic seizures is already high. The
reviewing 2500 EEG interpretations by six experienced clinical
interictal EEG should be used predominantly to classify
neurophysiologists, that the probability that an EEG would be
epilepsy syndromes and to help choose the right drug when
interpreted as epileptiform varied significantly depending on
treatment is indicated, and it may have prognostic value in
the neurologist reader.3 Taken together, these results show that
some specific circumstances.3 The diagnosis of epilepsy
agreement in visual interpretation of EEGs across centers and
based solely on EEG results without adequate knowledge of
within a single community is not ‘almost perfect’.
the clinical signs of seizures, or rejection of this diagnosis
For diagnostic purposes, it is worth noting that classification
because of normal interictal EEG findings, are frequent mis-
of epilepsy syndromes includes more specific interpretations
takes, as shown in the literature.1–5 If paroxysmal events are
of the type and location of epileptiform discharges than Stroink
not straightforward epileptic seizures by history, one has to
et al. required for their study. When neurologists’ readings on
consider alternative diagnoses, wait until the events become
more specific epileptic findings are compared, agreement is
clearer in time, request a home video if possible, request a
also lower. In a random sample of 255 neurologists asked to
video-EEG, or refer the child to an experienced paediatric
read 10-second samples of 12 EEGs, among the 100 who
neurologist or epileptologist. Thus, an EEG should be
agreed to participate there was wide variation in interpreta-
obtained only if the clinical suspicion of epileptic seizures is
high, as was the case in our study,8 and not when children pre-
The authors have done a commendable job in showing us
sent unclear events or non-epileptic complaints.1–5
that it is possible for visual EEG interpretations in selected situ-
Two of the five clinical neurophysiologists in our study
ations to have high agreement. However, there is more work to
were co-authors of our paper. None of these five was a mem-
be done before we can tell our patients and colleagues that
ber of our study group DSEC. However, they are all full-time,
neurologists interpret EEGs consistently.
board-certified clinical neurophysiologists with a great dealof experience. This has probably influenced our results, as
has the selection of the children. Moreover, in daily practicethe quality of EEG reports and consequent diagnosis and
classification of epilepsy in children depends on regular dis-
Cincinnati Children’s Hospital Medical Center, USA.
cussion between clinicians and clinical neurophysiologists. This method of working may alone be an important factor in
Correspondence to: email@example.com
improving the interrater reliability, as Gilbert remarks. Another factor causing diverging EEG results, not mentioned
by Gilbert, may be the interval between seizure and EEG.3,6 A
1. Stroink H, Schimsheimer RJ, de Weerd AW, Geerts AT, Arts WF,
longer interval lowers the chance of epileptiform discharges.
Peeters EA, Brouwer OF, Boudewijn Peters A, van Donselaar CA. (2006) Interobserver reliability of visual interpretation of
We only performed an interrater study for EEG abnormalities
electroencephalograms in children with newly diagnosed
and did not study syndrome classification (we published such
seizures. Dev Med Child Neurol 48: 374–377.
a study earlier7). Epilepsy classification depends on the results
2. Gilbert DL, Sethuraman G, Kotagal U, Buncher CR. (2003) Meta-
of the EEG in combination with the clinical symptoms. For
analysis of EEG test performance shows wide variation among
example, if a clinician requests an EEG because of seizures
studies. Neurology 60: 564–570.
3. Gilbert DL, Gartside P. (2002) Factors affecting the yield of
with diminished consciousness, automatisms, and postictal
pediatric EEGs in clinical practice. Clin Pediatr (Phila) 41: 25–32.
confusion and the EEG shows centrotemporal spikes with a
4. Williams GW, Luders HO, Brickner A, Goormastic M, Klass DW.
normal background pattern, the EEG findings do not match
(1985) Interobserver variability in EEG interpretation. Neurology
the clinical symptoms; they are probably coincidental and do
Gilbert has previously shown that EEGs are regularly
requested unjustifiably without a high suspicion of epilepticseizures and even for other reasons, and that prognostic value
varies widely between studies. We showed that the interob-
SIR–We thank Dr Gilbert for his valuable comments, however,
server reliability of EEG descriptions can be high with the use
we feel that the object of our study was somewhat different
of criteria for EEG abnormalities, when EEGs are requested by
from the studies of Gilbert et al.1,2 They investigated the
experienced physicians for children with a high suspicion of
value of electroencephalograms (EEGs) of children request-
epilepsy and are seen and read by experienced, certified clini-
ed during daily practice1 and performed a meta-analysis of
Developmental Medicine & Child Neurology 2006, 48: 1006–1011
Much work needs to be done in teaching physicians and
‘Genetic testing for myotubular myopathy despite muscle
clinical neurophysiologists treating children with paroxysmal
biopsy without centrally located nuclei’
events on how to improve the quality of diagnosis and treat-
SIR–I commend your journal and authors de Goede et al. on
ment of these children. Preferably, only a few selected physi-
the fascinating article ‘Muscle biopsy without centrally locat-
cians in a general paediatric practice will see children with
ed nuclei in a male child with mild X-linked myotubular
possible epilepsy, to gather enough experience and training
myopathy’.1 The authors described a male with a congenital
within this field. EEGs should be read by experienced clinical
myopathy, who lacked a more specific diagnosis despite
neurophysiologists who discuss the results with the clini-
various tests including repeat muscle biopsy (which did not
cians. In case of doubt, the child should be referred to an
show centrally located nuclei). Years later, the child’s mother
experienced paediatric neurologist or epileptologist.
learned that her cousin’s son had a clinically similar myopa-thy where muscle biopsy indeed did show centrally locatednuclei, prompting genetic testing which, in both children,
was positive for the same MTM1 (myotubularin) mutation,thus making the diagnosis of X-linked myotubular myopathy
This is a landmark article, clearly showing the growing
importance of genetic testing for myotubular myopathy
(MTM) and other forms of centronuclear myopathy (CNM).
Many other cases in practice and in the literature have shown
that a conclusive diagnosis of XL-MTM cannot be made mere-
ly based on centrally located nuclei on muscle biopsy, which
looks similar in congenital myotonic dystrophy as well as
among the various different forms of MTM/CNM. Meanwhile,family histories are limited by memory, undisclosed paterni-
Departments of Paediatric Neurology at:
ty, and lost contact with relatives. Further, the clinical presen-
tations show substantial variability and overlap among these
bMedical Centre Haaglanden, the Hague;
myopathies. Thus, we have known for years that myopathy
cDutch Epilepsy Clinics Foundation, Zwolle;
patients with centrally located nuclei need genetic testing to
more definitively diagnose the specific myopathy. However,
eUniversity Medical Centre, Groningen;
this article presents a novel revelation that MTM/CNM genet-
fUniversity Medical Centre, Utrecht, the Netherlands.
ic testing is indicated even in myopathy cases where the mus-cle biopsy does not show centrally located nuclei.
*Correspondence to: H.Stroink@Elisabeth.nl
The knowledge gained from this single article has the
potential to shift substantially the diagnostic algorithm in
congenital myopathies, leading to increased genetic testing
1. Gilbert DL, Gartside PS. (2002) Factors affecting the yield of
and more accurate diagnoses. This, in turn, would allow for
pediatric EEGs in clinical practice. Clin Pediatr 41: 25–32.
more accurate genetic counselling for affected families and
2. Gilbert DL, Sethuraman G, Kotagal U, Buncher CR. (2003) Meta-
relatives, as well as an increased likelihood of appropriate
analysis of EEG test performance shows wide variation among
patient identification for research studies and eventual gene-
studies. Neurology 60: 564–570.
3. Stroink H, Brouwer OF, Arts WF, Geerts AT, Peters AC, van
specific treatments. I praise the authors and this journal, and
Donselaar CA. (1998) The first unprovoked, untreated seizure in
I hope that the medical and research community worldwide
childhood: a hospital-based study of the accuracy of the
will take note of this article’s importance and implications.
diagnosis, rate of recurrence, and long term outcome afterrecurrence. Dutch study of epilepsy in childhood. J NeurolNeurosurg Psychiatry 64: 595–600.
4. Stroink H, van Donselaar CA, Geerts AT, Peters AB, Brouwer OF,
Arts WF. (2003) The accuracy of the diagnosis of paroxysmal
events in children. Neurology 60: 979–983. University of Medicine and Dentistry of New Jersey, New
5. Chadwick D, Smith D. (2002) The misdiagnosis of epilepsy. BMJJersey Medical School, Newark, New Jersey, USA.
6. King MA, Newton MR, Jackson GD, Fitt GJ, Mitchell LA, Silvapulle
MJ, Berkovic SF. (1998) Epileptology of the first-seizure
Correspondence to: Patrick.Foye@umdnj.edu
presentation: a clinical, electroencephalographic, and magneticresonance imaging study of 300 consecutive patients. Lancet352: 1007–1011.
7. Stroink H, van Donselaar CA, Geerts AT, Peters AC, Brouwer OF,
1. de Goede CG, Kelsey A, Kingston H, Tomlin PI, Hughes MI.
van Nieuwenhuizen O, de Coo RF, Geesink H, Arts WF. (2004)
(2005) Muscle biopsy without centrally located nuclei in a male
Interrater agreement of the diagnosis and classification of a first
child with mild X-linked myotubular myopathy. Dev Med Child
seizure in childhood. The Dutch study of epilepsy in childhood.
J Neurol Neurosurg Psychiatry 75: 241–245.
8. Stroink H, Schimsheimer RJ, de Weerd AW, Geerts AT, Arts WF,
Peeters EA, Brouwer OF, Boudewijn Peters Avan Donselaar CA. (2006) Interobserver reliability of visual interpretation ofelectroencephalograms in children with newly diagnosedseizures. Dev Med Child Neurol 48: 374–377.
EL FILÓSOFO COMO INTELECTUAL PÚBLICO 28/08/2010 Alberto Buela ∗ Le ha pasado a muchos, y nos ha pasado también a nosotros, que después de dictar clase durante años en la universidad, dejaron la enseñanza para limitarse a la investigación propia, a pensar sin ataduras, programas ni horarios. Pero, por qué se toma este tipo de decisión tan vital: a) Por la íntima y
J Clin Periodontol 2007; 34: 913–916 doi: 10.1111/j.1600-051X.2007.01140.xDivision of Periodontics, Section of Oral andDiagnostic Sciences, Columbia UniversityCollege of Dental Medicine, New York, NY,USALalla E. Periodontal infections and diabetes mellitus: when will the puzzle becomplete? J Clin Periodontol 2007; 34: 913–916. doi: 10.1111/j.1600-051X.2007.01140.x. The article in last mont