P

Pain and the Guillain-Barré syndrome in children

under 6 years old
Dang Khoa Nguyen, MD, Stacey Agenarioti-Bélanger, MD, and Michel Vanasse, MD, FRCP(C)

During a 15-year period, 29 children, under the age of 6 years, with acute
pital (Montreal) from 1981 to 1996. The
clinical series consisted of 29 children
Guillain-Barré syndrome were seen at our institution. A review of their (16 boys and 13 girls) under 6 years old
charts revealed that pain was a symptom in all patients and was present on with a diagnosis of GBS according to
admission in 79% of cases. Pain was often the most important symptom and published criteria.6 Electrophysiologic
led to misdiagnosis in 20 patients (69%). In 11 of these children, symptoms studies were performed in all patients,
were present for more than a week before the correct diagnosis was made. and CSF was analyzed for cell count
The most common pain syndrome was back and lower limb pain, present in and protein concentration in 28 of 29.
83% of patients. Pediatricians should consider Guillain-Barré syndrome in
CSF Cerebrospinal fluid
their differential diagnosis when faced with a child who has lower limb pain
GBS Guillain-Barré syndrome
and areflexia. (J Pediatr 1999;134:773-6) IVIG Intravenous immunoglobulin

Illustrative Case Histories

Guillain-Barré syndrome is a rapidly
progressive, acute, inflammatory poly-
radiculoneuropathy. It typically pre-
sents as an acute ascending symmetri-
cal weakness with areflexia. Although
the etiology of GBS remains unknown,
it is generally accepted that an immune
response is directed against antigens on
the myelin or axon, or perhaps both.1,2
An infection within the past month is
found in 50% to 70% of cases. The inci-
dence of GBS in children less than 17
years old is estimated at 0.8 per 100,000
person-years.3 Biochemical analysis of
cerebrospinal fluid usually shows ele-
From the Division of Neurology, Department of Pedi-
atrics, Hôpital Sainte-Justine and Université de Mon-
tréal, Montreal, Quebec, Canada.
Submitted for publication Feb 20, 1998; revi-
sions received Sept 4, 1998, and Feb 4, 1999;
accepted Mar 8, 1999.
Reprint requests: Michel Vanasse, MD, Lab-
oratoire EEG, Hôpital Sainte-Justine, 3175
Côte Sainte-Catherine, Montreal, Quebec,
H3T 1C5 Canada.
Copyright © 1999 by Mosby, Inc.
0022-3476/99/$8.00 + 0 9/22/98506
vated protein, and electrophysiologic
studies demonstrate acute neuropathy.2
Most GBS cases are demyelinating, but
axonal GBS is now well recognized.
Plasmapheresis treatment halts pro-
gression of GBS and hastens recovery.
Intravenous immunoglobulin treatment
has also been shown to be effective.4
Pain is a frequent feature of GBS5 in
children, as well as in adults. However,
its diagnosis may be more difficult in
children because the history and their
cooperation during the neurologic ex-
amination are often limited. In our ex-
perience, this is particularly true in
younger children and frequently leads
to misdiagnosis. To verify this theory,
we conducted a retrospective study
and report a series of GBS in children
under 6 years old seen at Ste-Justine
Hospital in Montreal.
PATIENTS AND
METHODS
We reviewed the charts of all children
with GBS admitted to Ste-Justine Hos-
PATIENT 1. Three days before admis-
sion, a 2-year-old boy presented to the
emergency department with intermit-
tent backache and abdominal pain after
a transitory viral illness. He had refused
to walk during the painful episode but
resumed playing when the pain dissi-
pated. The patient was diagnosed with
constipation, after an abdominal x-ray
film was obtained, and was discharged
home. The following day, the boy re-
turned to the emergency department.
He was now irritable, had difficulty sit-
ting alone, and refused to stand. He
continued to complain of abdominal
pain and occasional hip pain. He was
discharged with the same diagnosis of
constipation. The next day, the pain had
progressed and spread to the lower
limbs. The patient was now anorexic
and asthenic. He complained of head-
ache and refused to walk. On physical
examination, the boy was noted to have
some neck stiffness and was hospital-
ized because of suspected meningitis.
Peripheral reflexes were diminished,
but the patient moved all 4 limbs. Rou-
tine laboratory test results were normal,

773
 NGUYEN, AGENARIOTI-BÉLANGER, AND VANASSE
Table I. Pain in children with GBS
No. of patients 29 (100%)
Pain on admission 23 (79%)
Pain during course of 29 (100%)
illness
Distribution of pain
Lower limb pain 24 (83%)
Neck stiffness 11 (38%)
Headache 7 (24%)
Visceral pain 3 (10%)
Dysesthetic extremity 1 (3%)
pain
including creatine kinase levels. The
lumbar puncture revealed an increased
CSF protein concentration of 1.04 g/L
with 11 white blood cells and 304 red
blood cells. Results of a lumbar spine
scan and scintigraphy were normal.
Electromyographic recordings on the
10th day of the illness confirmed the
presence of a demyelinating and axonal
polyradiculoneuropathy. During the
hospitalization, the patient’s pain de-
creased slightly and his gait improved.
He received physical therapy and re-
covered completely in 2 months.
PATIENT 2. A 4-year-old boy was seen
a week before admission by an ortho-
pedic surgeon because of a 2-week
history of bilateral leg pain that wors-
ened on ambulation. A diagnosis of
femoral head avascular necrosis was
made. The patient was subsequently
brought to the emergency department
because of persistent leg pain. He was
now refusing to walk and had areflex-
ia with possible leg weakness that
could not be better defined. The pres-
ence of an elevated CSF protein con-
centration (0.91 g/L) in an acellular
spinal fluid combined with elec-
tromyographic findings of a demyeli-
nating polyradiculoneuropathy were
compatible with a diagnosis of GBS.
The patient’s condition was stable
during the first few days of hospital-
ization. After treatment with IVIG, he
began to experience improvement,
774
THE JOURNAL OF PEDIATRICS
JUNE 1999
Table II. Initial diagnoses (29 children) aching lower limb pain, exacerbated by
No. of straight leg raising. Twenty of the 23
Diagnosis patients patients who had pain on admission
presented with lower limb pain, and 4
GBS 9 other patients experienced limb pain
Myositis 5 during the course of illness. Myalgic
Meningitis 4 pain was often associated with this syn-
Encephalitis 3 drome because the pain was also elicit-
Cerebellar tumor 1 ed by local muscle palpation. Although
Acute cerebellar ataxia 1 no typical pattern was found, headache
Discitis 1 was noted in 24% of the patients. Ab-
Femoral head avascular 1 dominal pain was rarely encountered
necrosis and was always associated with leg
Muscular dystrophy 1 pain. Among the children capable of re-
Myasthenia gravis 1 porting sensory symptoms other than
Constipation 1 pain, only one reported dysesthetic ex-
Functional (somatization) 1 tremity pain. Eleven patients (38%)
with leg pain on examination were also
found to have neck stiffness.
Cranial nerve palsies were rare; only 2
and complete recovery was noted on patients had ophthalmoplegia, and 1 had
follow-up 3 months later. facial diplegia. Twenty-seven of 29
(93%) patients had evidence of lower
limb weakness. On admission, 25 pa-
RESULTS tients (86%) were found to have areflex-
ia in the lower limbs, and the remaining
Between 1981 and 1996, 29 children patients had hyporeflexia (14%). Re-
(16 boys and 13 girls) under 6 years of flexes in the upper limbs varied from
age were diagnosed with GBS at our normoreflexia to areflexia. Six patients
hospital. Their mean age was 3 years had labile blood pressure (mostly transi-
and 8 months (range, 11 months to 5 tory hypertension), and 3 had arrhyth-
years and 9 months). The onset of mia (2 had bradycardia and 1 had nodal
GBS was preceded by an infectious ill- escape rhythm). Three patients had
ness in 24 of 29 (83%) of the patients. apnea that resolved spontaneously, and
Patients had no prior significant or 2 had respiratory distress. One of these
concomitant diseases, except for one required intubation and assisted ventila-
patient who had a history of apnea tion. She later died of acute respiratory
spells. However, he did not have any distress syndrome and septic shock at
respiratory symptoms. the age of 4 years. Most of our patients
Pain was evident or reported in 23 received only physical therapy because
patients (79%) on admission (Table I). IVIG and plasma exchanges were not
Typically, pain was the initial and most yet recognized treatments for GBS at
important symptom in many of these the time of their diagnosis. One patient
patients. This led to a misdiagnosis in was treated with plasmapheresis, and 3
20 patients (69%) (Table II). More- other patients received IVIG. All 4 ex-
over, as illustrated by the case histories, perienced improvement after treatment.
it may take several days or even weeks An additional patient received both
before the correct diagnosis of GBS is treatments: IVIG was given initially, re-
made. In fact, 11 children had symp- sulting in some improvement; and
toms for a week or more before the di- plasmapheresis was given afterward, re-
agnosis of GBS was made. The promi- sulting in further improvement.
nent pain syndrome found in our The most commonly prescribed anal-
patient population was bilateral deep gesic was acetaminophen (38%), but 3
THE JOURNAL OF PEDIATRICS
VOLUME 134, NUMBER 6
patients (10%) required codeine. One
patient’s pain was refractory to both
medications. This patient demonstrated
a significant reduction in pain after
IVIG treatment. Another patient had
marked pain reduction with prednisone.
On follow-up, data were available
for 21 of the 28 surviving patients. One
patient had died as the result of an ac-
cident. The remaining 20 patients had
completely recovered, although 4
showed clumsiness (especially when
they were tired) and some had persis-
tent hyporeflexia.
DISCUSSION
Patients with GBS typically present
with ascending motor paralysis with
areflexia. However, retrospective and
prospective reports on adults with
GBS recognize pain as a common
symptom. In a recent study 89% of
adults with GBS reported pain during
the course of their illness. Moreover,
pain intensity on admission was found
to be correlated with neurologic dis-
ability on admission, but it was not a
predictor of poor prognosis.5 Other in-
vestigators also reported pain as a pri-
mary complaint in pediatric GBS,
sometimes even preceding the onset of
paralysis.7-10 Sakakihara et al7 noted
that limb pain was the initial symptom
in 53.4% of the children over 5 years
old and in 24% of children under 5
years old. In the latter group limb pain
eventually occurred in 52% of the pa-
tients during the course of the disease.
Royden Jones9 reported that pain was
the presenting symptom in 20% of chil-
dren, especially in those less than 10
years old. In the group of patients pre-
sented in this report, various types of
pain were noted in 79% of the children
under 6 years old. More specifically,
lower limb pain was present in 69% of
the patients at admission, and during
the course of illness, this number in-
creased to 83%. A more detailed de-
scription of the lower limb pain was im-
possible because of the lack of details
NGUYEN, AGENARIOTI-BÉLANGER,
obtainable from children under 6 years
old. However, we suspect that it is com-
parable to the pain experienced by
adult patients. Ropper and Shahani11
analyzed prospectively the clinical fea-
tures of pain in adult patients with
GBS. They reported that the most
common description of pain approxi-
mated the discomfort experienced after
a vigorous exercise (“charley horse”).
In another prospective study the most
frequent pain syndrome was described
as deep aching or throbbing pain in the
low back region with radiation into the
buttocks, thighs, and occasionally the
calves, which was exacerbated by
straight leg raising.5
Detection of limb weakness at the
onset of GBS may be quite difficult in
young children, especially in those
who are unable to express themselves.
Young children refuse to walk if it is
painful, and it is therefore difficult to
assess the presence of limb weakness.
Moreover, if they are able to walk,
their gait may be unsteady because of
pain and may be misinterpreted as an
ataxic gait. The lower limb pain may
be so striking that it often leads to di-
agnostic difficulties. For instance,
lower limb pain could lead to a misdi-
agnosis of myositis, nuchal rigidity
caused by meningitis, and unsteady
gait caused by acute cerebellar ataxia
or cerebellar tumor. Furthermore, as
noted by Royden Jones,10 severe
lower limb pain with significant irri-
tability, headache, and vomiting can
evoke a misdiagnosis of encephalitis.
The etiology of back and lower limb
pain in GBS is probably multifactorial.
Acute back and leg pain exacerbated
by straight leg raising provides indirect
evidence that traction on inflamed
nerve roots could be responsible for
some of the pain.5 Irritation of the nervi
nervorum, which innervates nerve
trunks, may also refer pain to the
paraspinal region through the dorsal
primary rami. However, Ropper and
Shahani11 suggested that the cause of
the lower limb pain most commonly
found in GBS is not “neuritic” but is
AND VANASSE
due to the acute neurogenic changes
seen in the weak muscles. It is notewor-
thy that one patient had significant re-
duction of pain intensity with pred-
nisone and another with IVIG, both
after an unsuccessful trial with anal-
gesics and nonsteroidal anti-inflamma-
tory drugs. This effect may be because
prednisone and IVIG have anti-inflam-
matory properties at the nerve root
level.6 Reduction of pain with cortico-
steroids has been described by others.11
Nevertheless, the drugs of choice in the
management of back and limb pain re-
main nonsteroidal anti-inflammatory
drugs, acetaminophen, and opioid anal-
gesics; whereas dysesthetic extremity
pain should be treated with drugs such
as carbamazepine, gabapentin, and tri-
cyclic antidepressants.5,12,13 Non-phar-
macologic modalities such as correct
positioning and appropriate splinting of
paretic limbs, pressure-relieving mat-
tresses, cold or warm pads, massage,
and regular passive physical therapy
should not be forgotten.13
In summary, this report, as well as
previous studies, strongly suggests that
in GBS, in addition to the classic pre-
sentation with rapid onset of symmet-
ric weakness, paresthesias, and are-
flexia, lower limb pain (and sometimes
back pain) may be major presenting
symptoms, especially in children less
than 6 years of age. Thus GBS should
be considered in the differential diag-
nosis of any child presenting with
acute extremity pain associated with
hyporeflexia or areflexia.
REFERENCES
1. Fulgham JR, Wijdicks EFM. Guillain-
Barré syndrome. Crit Care Clin 1997;
13:1-15.
2. Ropper AH. The Guillain-Barré syn-
drome. N Engl J Med 1992;326:1130-6.
3. Beghi E, Kurland LT, Mulder D,
Wiederholt WC. Guillain-Barré syn-
drome: clinicoepidemiologic features
and effect of influenza vaccine. Arch
Neurol 1985;42:1053-7.
4. Asbury AK, McKhann GM. Changing
775
 NGUYEN, AGENARIOTI-BÉLANGER, AND VANASSE THE JOURNAL OF PEDIATRICS
JUNE 1999

view of Guillain-Barré syndrome. Ann
Neurol 1997;41:287-8.
5. Moulin DE, Hagen N, Feasby TE,
Amireh R, Hahn A. Pain in Guillain-
Barré syndrome. Neurology 1997;48:
328-31.
6. Asbury AK, Cornblath DR. Assess-
ment of current diagnostic criteria for
Guillain-Barré syndrome. Ann Neurol
1990;27:S21-4.
7. Sakakihara Y, Kamoshita S. Age-asso-
ciated changes in the symptomatology
of Guillain-Barré syndrome in chil-
dren. Dev Med Child Neurol 1991;33:
611-6.
8. Rantala H, Uhari M, Niemela M. Oc-
currence, clinical manifestations, and
prognosis of Guillain-Barré syndrome.
Arch Dis Child 1991;66:706-9.
9. Royden Jones H Jr. Guillain-Barré
syndrome in children. Curr Opin Pedi-
atr 1995;7:663-8.
10. Royden Jones H Jr. Childhood Guil-
lain-Barré syndrome: clinical presenta-
tion, diagnosis, and therapy. J Child
Neurol 1996;11:4-12.
11. Ropper AH, Shahani BT. Pain in Guil-
lain-Barré syndrome. Arch Neurol
1984;41:511-4.
12. Khatri A, Pearlstein L. Pain in Guil-
lain-Barré syndrome [letter]. Neurolo-
gy 1997;49:1474.
13. Pentland B, Donald SM. Pain in the
Guillain-Barré syndrome: a clinical re-
view. Pain 1994;59:159-64.

O N THE MOVE?
Send us your new address at least six weeks ahead

Don’t miss a single issue of the journal! To ensure prompt service when you change your address,
please photocopy and complete the form below.
Please send your change of address notification at least six weeks before your move to ensure continued service.
We regret we cannot guarantee replacement of issues missed due to late notification.
JOURNAL TITLE:
Fill in the title of the journal here.

OLD ADDRESS: NEW ADDRESS:

Affix the address label from a recent issue of the journal here. Clearly print your new address here.

Name

Address

City/State/ZIP

COPY AND MAIL THIS FORM TO: OR FAX TO: OR PHONE:

Journal Subscription Services 314-432-1158 1-800-453-4351
Mosby, Inc. Outside the U.S., call
11830 Westline Industrial Dr. 314-453-4351
St. Louis, MO 63146-3318

776