Brain Dev. 1997
Jul;19(5):323-5.
Single dose
immunoglobulin therapy
for childhood
Guillain-Barre syndrome.
Zafeiriou DI,
Kontopoulos EE, Katzos
GS, Gombakis NP,
Kanakoudi FG.
1st Pediatric Clinic,
Aristotelian University
of Thessaloniki, Greece.
To establish the
efficacy of intravenous
immunoglobulins (IVIG)
in the treatment of
acute Guillain-Barre
syndrome (GBS), we
treated nine consecutive
pediatric cases (age
2.5-13.5 years)
fulfilling the criteria
for GBS with a single
dose of IVIG (Sandoglobulin;
2 g/kg/BW). None of the
patients experienced any
IVIG related
side-effects. The mean
time required to improve
by at least one grade on
the functional GBS scale
after IVIG treatment was
3.5 days, while the mean
period to regain
ambulation was 11.2
days. Full mobilization
without evidence of
relapse in the follow-up
period (mean 14.5
months) was noted in all
but one patient who
relapsed after 5 months.
We conclude that the
early use of a single
IVIG dose may prevent
further progression of
the disease, thus
shortening the clinical
course of childhood GBS.
The most beneficial IVIG
dose regimen remains to
be determined by
controlled trials.
Publication Types:
Clinical Trial
PMID: 9253484 [PubMed -
indexed for MEDLINE]
Pediatr Int. 2003
Oct;45(5):543-9.
High-dose immunoglobulin
therapy for
Guillain-Barre syndrome
in Japanese children.
Yata J, Nihei K, Ohya T,
Hirano Y, Momoi M,
Maekawa K, Sakakihara Y;
Study Group for
Pediatric Guillain-Barre
Syndrome.
BACKGROUND:
Guillain-Barre syndrome
(GBS) is an acute
acquired demyelinating
polyneuropathy, presumed
to be immune-mediated.
Intravenous
immunoglobulin (IVIg)
has been used to treat
GBS and was found to be
effective. However, a
well-controlled study of
pediatric GBS has not
been conducted in Japan.
Therefore, to evaluate
the efficacy of IVIg in
the treatment of GBS, an
open-labeled study was
performed in pediatric
patients. METHODS:
Participants in the
study were required to
be younger than 15 years
old, and diagnosed as
having moderate or
severe GBS. IVIg (400
mg/kg per day) was
administered to patients
for five consecutive
days. Predefined outcome
measures were defined on
a seven-point scale of
motor function (Hughes'
functional grade [FG]).
RESULTS: Eleven patients
were treated with IVIg.
The median time taken to
improve by one grade on
the FG scale was 10.0
days after initial
treatment. Two weeks
after initial treatment,
72.7% of patients
treated with IVIg
improved by one or more
grades, and 36.4%
improved by two or more
grades, measured on the
FG scale. After 4 weeks
an improvement by one or
more grades was observed
in 81.8% of patients,
and two or more grades
in 63.6% of patients.
These improvement rates
were markedly greater
than would occur with
the natural course of
GBS1. Adverse events
(subjective symptoms or
abnormal laboratory
findings) were observed
in four patients,
although all were
temporary and mild.
CONCLUSIONS: The authors
conclude that IVIg is a
safe and effective
treatment for childhood
GBS, which shortens the
time to recovery.
Publication Types:
Clinical Trial
PMID: 14521529 [PubMed -
indexed for MEDLINE]
Pediatrics. 2005
Jul;116(1):8-14.
Intravenously
administered
immunoglobulin in the
treatment of childhood
Guillain-Barre syndrome:
a randomized trial.
Korinthenberg R, Schessl
J, Kirschner J, Monting
JS.
Division of
Neuropediatrics and
Muscular Disorders,
Department of Pediatrics
and Adolescent Medicine,
University Hospital
Freiburg,
Mathildenstrasse 1,
D-79106 Freiburg,
Germany.
OBJECTIVE: To determine
the optimal treatment
for childhood
Guillain-Barre syndrome
(GBS). METHODS: We
performed a randomized,
multicenter study of GBS
according to
international diagnostic
criteria. In study 1
(early treatment),
children able to walk
unaided for 5 meters
were randomized for 1
g/kg intravenously
administered
immunoglobulin (IVIG)
over 2 days or no
treatment. The primary
outcome measure was the
degree of disability at
nadir. In study 2
(treatment for severe
GBS), children unable to
walk 5 meters unaided
were randomized for 1
g/kg IVIG over 2 days or
0.4 g/kg IVIG over 5
days. The primary
outcome measure was the
number of days needed to
regain the ability to
walk unaided. Children
randomized for no
treatment in study 1
could enter study 2 if
loss of unaided walking
occurred. RESULTS:
Ninety-five children
with GBS were registered
in 40 months. Twenty-one
children were randomized
in study 1 and 51 in
study 2 (5 after
deterioration in study
1). Twenty-eight
children were not
randomized for various
reasons. Eleven of 21
patients in study 1 lost
the ability to walk
unassisted and 6 were
bedridden, with no
statistically
significant difference
between the children
initially randomized for
treatment versus no
treatment. Recovery
occurred faster in the
group randomized for
early treatment. In
study 2, recovery did
not differ significantly
between the children
treated for 2 days
versus 5 days (median
time to unaided walking:
19 days vs 13 days).
Secondary transient
deterioration in the
disability score
occurred more frequently
in the group with the
2-day regimen than in
the group treated for 5
days (5 of 23 patients
vs 0 of 23 patients).
Multivariate analysis
with Cox regression
showed that disease
severity at the nadir
was the only prognostic
factor for recovery.
CONCLUSIONS: Treatment
with IVIG before loss of
unaided walking did not
give rise to a less
severe course, but
recovery occurred
somewhat faster.
However, given the small
number of patients, the
power of this conclusion
is low. For treatment
after loss of unaided
walking, there was no
significant difference
in the effectiveness of
2 g/kg IVIG administered
over 2 days versus 5
days. Early "relapses"
occurred more frequently
after the shorter
treatment regimen.
PMID: 15995024 [PubMed -
indexed for MEDLINE]
Neuropediatrics. 1999
Aug;30(4):190-6.
Chronic inflammatory
demyelinating
polyradiculoneuropathy
in children and their
response to treatment.
Korinthenberg R.
Department of
Neuropaediatrics and
Muscular Disorders,
Paediatric University
Hospital, Freiburg,
Germany.
PURPOSE OF THE STUDY: To
collect data on both the
natural history of
chronic inflammatory
demyelinating
polyradiculoneuropathy (CIDP)
in children and their
response to treatment.
STUDY DESIGN:
Retrospective
multicentre study, using
standardised criteria
for the evaluation of
hospital records and
semi-quantitative
scoring of disability.
RESULTS: A total of 21
patients (age range 2-14
years) were observed
clinically over a median
period of four years. At
the peak of the disease,
12 children were unable
to walk. None of the
patients required
artificial ventilation.
Most of the children
were treated with
corticosteroids or
high-dosage
immunoglobulins (2 g/kg
body weight), or both.
Nine experienced
spontaneous as well as
treatment-related
remissions and relapses;
in twelve the degree of
disability changed
exclusively parallel to
modifications of the
treatment.
Corticosteroids were
used as the first-line
drug for 11 patients and
were effective for
eight; prolonged
treatment (up to 2
years) was usually
necessary.
Administration of
high-dosage intravenous
immunoglobulins was used
for 14 children,
resulting in significant
and rapid clinical
improvement in 12. In
eight patients the
treatment with
immunoglobulins had to
be repeated at regular
intervals for up to four
years. At the last
follow-up visit, 12/21
patients were off
treatment for 3 months
to 11 years, showing
none or only slight
symptoms and signs; of
those still receiving
treatment three were in
a stable condition, five
exhibited significant
fluctuation of symptoms,
and one was unable to
walk unaided.
CONCLUSION: In the
majority of children
with CIDP, the
protracted and
debilitating course of
the disease can be
alleviated by treatment
with either
corticosteroids or
immunoglobulins. For
patients resistant to
this treatment an
escalating regimen with
plasmapheresis,
immunosuppressive drugs
or interferon-alpha
should be considered.
Publication Types:
Multicenter Study
PMID: 10569210 [PubMed -
indexed for MEDLINE]
Review: 1
1: Pediatr Neurol. 2001
Mar;24(3):177-82.
Chronic inflammatory
demyelinating
polyneuropathy in
childhood.
Connolly AM.
Department of Neurology,
St. Louis Children's
Hospital, Washington
University of Medicine,
St. Louis, Missouri
63110, USA.
Chronic inflammatory
demyelinating
polyneuropathy (CIDP) in
children is relatively
rare. However, it has
been recognized for many
years. In patients
presenting with this
disease, subacute onset
of weakness usually
develops over at least 2
months and often
progresses to a loss of
ambulation. Some
children's initial
presentations may mimic
Guillain-Barre syndrome.
Dysasthesias are common.
Males are affected more
than females, and
antecedent illnesses or
vaccinations occur in
approximately half of
patients. Physical
examination reveals
diffuse, proximal
greater than distal
weakness, with an
absence or depression of
muscle stretch reflexes.
Electrophysiology
confirms demyelination,
and spinal fluid
examination demonstrates
albuminocytologic
dissociation. The
clinical presentation,
diagnosis, and prognosis
of childhood CIDP are
reviewed. Treatment and
immunologic features are
also discussed in this
article.
Publication Types:
Review
PMID: 11301217 [PubMed -
indexed for MEDLINE]
1: Neuromuscul Disord.
2000 Aug;10(6):398-406.
Childhood chronic
inflammatory
demyelinating
polyneuropathy: clinical
course and long-term
outcome.
Ryan MM, Grattan-Smith
PJ, Procopis PG, Morgan
G, Ouvrier RA.
Department of Neurology,
The Royal Alexandra
Hospital for Children,
Sydney, Australia.
We reviewed the clinical
history,
electrophysiologic and
pathologic findings, and
response to therapy of
16 children with chronic
inflammatory
demyelinating
polyneuropathy. The
majority presented with
lower limb weakness.
Sensory loss was
uncommon. The illness
was monophasic in seven
children, relapsing in
six, and three had a
slowly progressive
course. All patients
were treated with
immunosuppressive
agents. In 11, the
initial treatment was
prednisolone. All had at
least a short-term
response but five went
on to develop a
relapsing course.
Intravenous
immunoglobulin was the
initial treatment in
four patients. Three
responded rapidly, with
treatment being stopped
after a maximum of 5
months. In resistant
chronic inflammatory
demyelinating
neuropathy, in addition
to prednisolone and
immunoglobulin, plasma
exchange, azathioprine,
cyclosporine,
methotrexate,
cyclophosphamide and
pulse methylprednisolone
were tried at different
times in different
patients. On serial
neurophysiologic testing
slowing of nerve
conduction persisted for
long periods after
clinical recovery.
Follow-up was for an
average of 10 years.
When last seen 14
patients were
asymptomatic, two having
mild residual deficits.
Childhood chronic
inflammatory
demyelinating neuropathy
responds to conventional
treatment and generally
has a favourable
long-term outcome.
PMID: 10899445 [PubMed -
indexed for MEDLINE]
: Eur J Paediatr Neurol.
1998;2(4):169-77.
Related Articles, Links
Childhood chronic
inflammatory
demyelinating
polyneuropathy.
Nevo Y.
The Institute for Child
Development, Division of
Pediatrics, Dana
Children's Hospital,
Sackler School of
Medicine, Tel Aviv
University, Israel.
Chronic inflammatory
demyelinating
polyneuropathy (CIDP) is
a chronic disorder of
the peripheral nervous
system with sensory and
motor involvement, and
insidious onset over a
period of months. In
children and adults,
both proximal and distal
muscles are affected.
Muscle stretch reflexes
are absent or depressed.
Laboratory findings
include elevated
cerebrospinal fluid
protein with no increase
of mononuclear cells.
Electrophysiological and
pathological studies
show evidence of
demyelination. No
control studies of the
efficacy of
immunomodulating therapy
in childhood CIDP are
available. However,
several studies have
indicated clinical
improvement after
treatment with
prednisolone,
plasmapheresis and
intravenous
immunoglobulin, but
disappointing results
with other
immunosuppressive
agents. While some
children have a
monophasic course, with
complete recovery,
others have a protracted
course, with either a
slowly progressive or a
relapsing-remitting
course, resulting in
prolonged morbidity and
disability.
PMID: 10726588 [PubMed -
indexed for MEDLINE]
Pain Med. 2002
Jun;3(2):119-27.
Human pooled
immunoglobulin in the
treatment of chronic
pain syndromes.
Goebel A, Netal S,
Schedel R, Sprotte G.
Klinik fur
Anaesthesiologie,
University Wurzburg,
Wurzburg, Germany.
Objective. To examine
the use of intravenous
immunoglobulin (IVIG) in
chronic pain. Design. A
prospective
multiple-dose,
open-label cohort study
in 130 consecutive
patients who suffered
from 12 chronic pain
syndromes. The largest
symptom groups were
(number of patients):
Fibromyalgia (48);
Spinal pain (20);
Complex regional pain
syndrome (CRPS, 11);
Peripheral neuropathic
pain (12); and Atypical
odontalgia or atypical
facial pain (11). All
patients had
insufficient pain relief
with established
treatments. Pain relief
was recorded using
average pain intensity
values as documented in
standardized diaries. A
specific treatment
protocol was developed,
and patients were
enrolled over a 36-month
period. Results.
Overall, 20% of patients
had>70% pain relief and
27.7% of patients
reported relief between
25% and 70%. Six
patients (4.6%) had
moderately increased
pain levels for a
duration of up to 9
weeks. Good relief, of
more than 70%, was found
in all major symptom
groups. Patients with
pain of short duration
(<2 years) reported high
relief rates (33.8% of
patients in this group
reported relief
openface>70%). No
serious adverse events
were reported.
Conclusions. IVIG may be
effective in patients
suffering from chronic
pain. Controlled studies
are needed to evaluate
the efficacy of IVIG in
these patients. Patients
with a good response to
IVIG may be models for
the study of neuroimmune
interactions in chronic
pain.
PMID: 15102158 [PubMed -
in process]
: Drugs.
2003;63(3):275-87.
Management of chronic
inflammatory
demyelinating
polyradiculoneuropathy.
Hughes RA.
Department of Clinical
Neurosciences, Guy's,
King's and St Thomas'
School of Medicine,
London, UK.
richard.a.hughes@kcl.ac.uk
This review briefly
describes current
concepts concerning the
nosological status,
pathogenesis and
management of chronic
inflammatory
demyelinating
polyradiculoneuropathy
(CIDP). CIDP is an
uncommon variable
disorder of unknown but
probably autoimmune
aetiology. The commonest
form of CIDP causes more
or less symmetrical
progressive or relapsing
weakness affecting
proximal and distal
muscles. Against this
background the review
describes the short-term
responses to
corticosteroids,
intravenous
immunoglobulin (IVIg)
and plasma exchange that
have been confirmed in
randomised trials. In
the absence of better
evidence about long-term
efficacy,
corticosteroids or IVIg
are usually favoured
because of convenience.
Benefit following
introduction of
azathioprine,
cyclophosphamide,
cyclosporin, other
immunosuppressive
agents, and
interferon-beta and
-alpha has been reported
but randomised trials
are needed to confirm
these benefits. In
patients with pure motor
CIDP and multifocal
motor neuropathy,
corticosteroids may
cause worsening and IVIg
is more likely to be
effective. General
measures to rehabilitate
patients and manage
symptoms, including foot
drop, weak hands,
fatigue and pain, are
important.
PMID: 12534332 [PubMed -
indexed for MEDLINE]
Neurology. 1997
Feb;48(2):321-8.
Chronic inflammatory
demyelinating
polyneuropathy: clinical
features and response to
treatment in 67
consecutive patients
with and without a
monoclonal gammopathy.
Gorson KC, Allam G,
Ropper AH.
Neurology Service, St.
Elizabeth's Medical
Center, Boston, MA
02135, USA.
We report the clinical
and EMG details of 67
consecutive patients
with strictly defined
chronic inflammatory
demyelinating
polyneuropathy (CIDP)
during a 4-year period
and compare responses to
treatment in patients
with idiopathic CIDP
(CIDP-I) and CIDP with
monoclonal gammopathy of
uncertain significance
(CIDP-MGUS). Patients
were examined an average
of 28 months after first
symptoms. There were
several variant
presentations that still
conformed to the
clinical and
electrophysiologic
definitions of CIDP,
including a pure motor
syndrome (10%), sensory
ataxic variant (12%),
mononeuritis multiplex
pattern (9%),
paraparetic pattern
(4%), and relapsing
acute Guillain-Barre
syndrome (16%). Pain was
more frequent than in
previous studies (42%).
Conduction block was the
commonest EMG
abnormality (detected in
at least one nerve in
73% of patients), but
only 31% had a pure
demyelinating neuropathy
and the majority had
some degree of axonal
change. Patients with
CIDP-MGUS had less
severe weakness, greater
imbalance, leg ataxia,
vibration loss in the
hands, and absent median
and ulnar sensory
potentials, but were as
likely as CIDP-I
patients to respond to
plasma exchange.
Seventeen of 44 patients
(39%) with idiopathic
CIDP improved for at
least 2 months with an
initial therapy.
Although the response
rates among plasma
exchange, IVIG, and
steroids were similar,
functional improvement
(Rankin score) was
greatest with plasma
exchange. Of 26 patients
who failed to respond to
an initial therapy, 9
(35%) benefited from an
alternative treatment,
and of the 11 who
required a third
modality 3 (27%)
improved. Overall, 66%
responded to one of the
three main therapies for
CIDP.
PMID: 9040714 [PubMed -
indexed for MEDLINE]
Diabetes Metab. 2001
Apr;27(2 Pt 1):155-8.
An unusual neuropathy in
a diabetic patient:
evidence for intravenous
immunoglobin-induced
effective therapy.
Romedenne P, Mukendi R,
Stasse P, Indekeu P,
Buysschaert M, Colin IM.
Department of Internal
Medicine, CHR-St Joseph
Medical Center, Mons,
Belgium.
We report the case of a
68-year old type-2
diabetic male patient
who was admitted to
hospital for progressive
weakness in the right
lower limb. Although his
metabolic control was
good, he lost more than
20 kg of weight. Despite
intensive physio- and
vitaminotherapy, his
neurological condition
kept on degrading with a
severe amyotrophy and
pain of the right thigh.
He was unable to walk
and to stand alone.
Besides a yet known
sensitive
polyneuropathy, the
electrophysiological
study revealed an
obvious motor
involvement with signs
of demyelination and
axonal degeneration.
Combined with the
albuminocytologic
dissociation observed in
the cerebrospinal fluid,
these specific clinical
and electrophysiological
features led us to
postulate a diagnosis of
inflammatory neuropathy.
The patient underwent a
treatment by
methylprednisolone and
immunoglobins that
rapidly induced a
striking improvement of
his neurological
condition. This case
report illustrates that
rare forms of neuropathy
such as inflammatory
neuropathies close to
chronic inflammatory
demyelinating
polyneuropathy (CIDP)
can occur in diabetic
patients and superimpose
on the more commonly
described forms of
neuropathies. It recalls
the importance of
recognizing CIDP-like
neuropathies because
unlike other forms of
neuropathy, inflammatory
neuropathies are
perfectly curable.
Publication Types:
Case Reports
PMID: 11353882 [PubMed -
indexed for MEDLINE]
J Neurol Sci. 2000 Feb
15;173(2):129-39.
, Links
The spectrum of chronic
inflammatory
demyelinating
polyneuropathy.
Rotta FT, Sussman AT,
Bradley WG, Ram Ayyar D,
Sharma KR, Shebert RT.
Department of Neurology,
University of Miami
School of Medicine, PO
Box 016960, Miami, FL,
USA.
Research criteria for
the diagnosis of chronic
inflammatory
demyelinating
polyneuropathy (CIDP)
were proposed by an Ad
Hoc Subcommittee of the
American Academy of
Neurology (AAN) in 1991,
and since then these
criteria have been
widely used in clinical
studies. We have been
impressed by the
frequent finding of
electrophysiological
changes of a
demyelinating neuropathy
in patients whose
clinical presentation
does not conform to the
usually accepted
clinical phenotype of
CIDP. To determine the
clinical spectrum of
CIDP, we conducted a
retrospective review of
patients of the
peripheral
electrophysiology
laboratory of the
University of
Miami-Jackson Memorial
Medical Center.
Diagnostic criteria for
acquired demyelination
of an individual nerve
were adapted from the
AAN research criteria
for the diagnosis of
CIDP (1991). Patients
were accepted for
inclusion when such
evidence was
demonstrated in at least
one motor nerve or at
least two sensory
nerves. We then reviewed
the clinical phenotype
and the underlying
etiology of the
neuropathy in these
cases. Eighty-seven
patients, 63 male and 24
female, age of onset
4-84 (mean 49.3) years,
met these inclusion
criteria. Forty-seven
patients (54%) had
distinct features
outside the usual
clinical presentation of
CIDP. Of these, 15 (17%)
had predominantly distal
features, 13 (15%) had
exclusively sensory
polyneuropathy; seven
(8%) had markedly
asymmetric disease,
seven (8%) had
associated CNS
demyelination, four (5%)
had predominant cranial
nerve involvement, and
one (1%) had only the
restless legs syndrome.
An associated medical
condition that may have
been responsible for the
acquired demyelinating
neuropathy was present
in 60% of the patients.
We conclude that
spectrum of CIDP is
broader than would be
indicated by the strict
application of the AAN
research criteria, and
that many of the cases
meeting more liberal
criteria frequently
respond to
immunosuppressive
therapy.
www.cidpusa.org
www.cidpusa.org/P/ivig.htm
http://www.cidpusa.org/disease.html
http://www.cidpusa.org/Lahore.html
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