Prognosis of Guillain-Barré Syndrome in Children.

The Guillain-Barré syndrome (GBS) is a severe post-infectious immune-mediated
polyradiculoneuropathy that may affect persons of all ages [van Doorn 2008].
GBS is characterised by a rapidly progressive weakness and sensory loss,
usually followed by a slow clinical improvement after treatment with
intravenous immunoglobulin. Despite this improvement, a considerable proportion
of patients develop a residual impairment and handicap. In adult patients, 20%
remain unable to walk and the majority of patients report residual deficits
several years after onset, including sensory deficits and severe fatigue
[Bernsen 2001, Garssen 2006]. They also report serious long-term impact on work
and private life [Bernsen 2002]. Previous studies in adult patients have
identified various clinical, neurophysiological and laboratory features that
are relates with outcome, including age, severity of disease in the acute
phase, preceding diarrhoea, axonal damage, anti-ganglioside antibodies and
polymorphisms in complement genes [Geleijns 2006, van Koningsveld 2007, van
Doorn 2008]. Prognostic models have been developed based on the prognostic
factors available in the acute phase of disease, to predict the outcome at six
months in individual patients [van Koningsveld 2007]. This information can be
used in clinical practice to inform patients and their relatives about the
prognosis and to conduct selective trials in patients with poorest outcome.
These prognostic models, however, are based predominantly on data obtained in
adult patients.
GBS also occurs in children with an incidence of 0.25 to 0.5 per
100.000 per year. Previous case studies showed that also in children the
neurological deficits may persist at least for months [Korinthenberg 2007].
However, in paediatric GBS the long-term outcome after more than six months and
the impact on development and quality of life is unknown. Children may have a
higher capacity to recover from GBS than adults because younger age in adults
is related to relatively good outcome. On the other hand, children are in a
more vulnerable state of life, which may increase the impact of the disease on
long-term psychological and physical development. The information on outcome in
adult patients can therefore not be applied to paediatric cases. In addition,
the prognostic models developed in adult patients are not validated in children
with GBS. Therefore it is currently difficult to provide information to
individual children and parents/care takers about the prognosis.

The present study aims to assess the long-term outcome of patients who
suffered from GBS during childhood. This outcome at least six months after
diagnosis will be determined in patients previously seen at the department of
Paediatric Neurology of the Sophia Children*s Hospital, Erasmus MC or other
centres (from 1987 till now). Most of those patients are currently adults. We
will focus on the residual neurological impairment, restrictions in activity
and participation, and quality of life, defined by various validated
questionnaires and physical tests. In addition, the residual nerve dysfunction
will also be determined by the CMAP scan, a routine non-invasive
neurophysiological examination that provides information on the type and extent
of nerve damage. All this information on long-term outcome will be related to
the clinical features in the acute phase of disease, which are available in the
patient files. In addition, DNA will be obtained to determine genetic
polymorphisms that are related to poor prognosis in adult patients with GBS.
The information on clinical and genetic prognostic factors will be underpowered
to develop definite prognostic models. However, the identification of candidate
prognostic factors for GBS in children will be validated further in future
prospective studies.

OBJECTIVES

Primary objective: To assess the long-term outcome of paediatric GBS with
respect to nerve physiology dysfunction, neurological impairment, restrictions
in daily activity and participation, and quality of life.

Secondary objective: To determine which demographic and clinical factors in the
acute phase of disease, and which genetic polymorphisms, are related with this
long-term outcome.

Observational cross-sectional cohort study.

. The endpoints will be determined by questionnaires that patients (and their
parents/care takers) can fill out at home within 1 hour. During the clinical
visit there will be an evaluation of 1 hour about these questionnaires where
patients can receive help for questions that were difficult to fill out. There
will also be a quality control of the data and some additional questionnaires
are filled out with help of the researchers. Than the patients will have a
routine neurological examination of less than half an hour. The vigorimeter and
Jamar dynamometer to determine grip strength are not painful and last less than
5 minutes and are part of this neurological examination.
· To obtain DNA to study genetic polymorphisms of the complement system saliva
from children and a blood sample or saliva from adults will be obtained. These
samples will be obtained in less than 5 minutes and carry no additional risks.
· To determine the nerve physiology a10 minutes CMAP scan of the ulnar nerve of
the non-dominant arm will be performed. With this routine non-invasive
neurophysiological technique a series of small electrical stimuli will be
applied at the wrist. These series are felt by the patients but are not painful
and carry no additional risks.
· The clinical visit including all tests will be performed in less than 3 hour,
but usually within 2 hours.