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Indian Pediatr 2013;50: 791-792 |
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Guillain-Barré Syndrome with Acute
Lymphoblastic Leukemia
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Binitha Rajeswari, *Syam Krishnan, *C Sarada, and
Parukuttyamma Kusumakumary
From Division of Pediatric Oncology, Regional Cancer
Centre; and *Department of Neurology, Sree Chitra Tirunal Institute for
Medical Sciences and Technology, Thiruvananthapuram, India.
Correspondence to: Dr Binitha Rajeswari, Lecturer,
Division of Pediatric Oncology, Regional Cancer Centre,
Thiruvananthapuram, Kerala 695 011, India.
Email: [email protected]
Received: March 08, 2013;
Initial review: March 26, 2013;
Accepted: April 09, 2003.
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Guillain-Barré syndrome (GBS) is
rarely reported in children with acute lymphoblastic leukemia and may be
difficult to differentiate from vincristine induced neuropathy. We
report two children with acute lymphoblastic leukemia on induction
chemotherapy who developed GBS. The diagnostic issues and potential
pathogenic mechanisms underlying GBS in pediatric patients with ALL are
discussed.
Keywords: Acute Lymphoblastic Leukemia,
Chemotherapy, Guillain-Barré Syndrome, Vincristine.
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There is substantial evidence for
autoimmune cause for Guillain-Barré syndrome (GBS), the most
frequent cause of acute flaccid paralysis[1]. GBS has been
reported in association with hematologic malignancies like
non-Hodgkin lymphoma, chronic lymphocytic leukemia and acute
lymphoblastic leukemia (ALL) in adults. There are only few
reports of GBS in children with ALL [2,3]. Differentiation
from other neuropathies is important from the therapeutic
point of view [3,4]. We report two cases of GBS in children
on induction chemotherapy for ALL and discuss the clinical
and electrophysiological features and potential mechanisms
of pathogenesis.
Case Report
Case 1: A 6-year-old boy was
evaluated for fever, pallor, cervical lymphadenopathy and
hepatosplenomegaly. Bone marrow aspiration and flow
cytometry was suggestive of T-cell acute lymphoblastic
leukemia. His CSF did not show blasts. He was started on
induction chemotherapy with prednisolone, vincristine,
daunorubicin and L-asparaginase. In the fifth week, he
developed symmetrical and gradually progressive proximal and
distal weakness of upper and lower limbs, progsessing to
dense quadriplegia over a period of 3 days. Weakness of
facial muscles was noticed on third day. He did not have any
sensory symptoms. The tendon reflexes were depressed
initially and totally disappeared by the third day.
Electrophysiological evaluation done on
fourth day of illness was suggestive of a motor axonopathic
polyradiculoneuropathy. The common peroneal nerves were
bilaterally unexcitable. Stimulation of the tibial, median
and ulnar nerves resulted in compound muscle action
potentials (CMAPs) with marked reduction of amplitude
bilaterally; conduction velocities were normal. F waves were
not elicitable from peroneal nerves; F waves from other
nerves showed prolonged latency. The sensory nerve action
potentials (SNAPs) were normal from all the tested nerves.
Correlating the clinical and electrophysiological findings,
acute motor axonal neuropathy (AMAN) – a subtype of GBS was
diagnosed. He was given a course of intravenous
immunoglobulin (IVIg) (0.4 g/kg/day) for 5 days. CSF was
re-examined on the eighth day which showed: glucose-55 mg/dL;
protein-163 mg/dL; cell count-2 lymphoayties/mm 3.
No blasts were detected in the CSF. The weakness began to
improve on the third day of treatment with immunoglobulin.
Eight weeks later, he had normal power of all the limbs and
was ambulant normally. He is presently on chemotherapy.
Case 2: A 2-year-old boy was
evaluated for fever, pallor and hepatosplenomegaly. Bone
marrow flow cytometry was diagnostic of precursor B acute
lymphoblastic leukemia with co-expression of CD 13 and CD33.
His CSF did not show blasts. He was started on induction
chemotherapy with prednisolone, vincristine, daunorubicin
and L-asparaginase. In the third week of chemotherapy, he
developed fever, cough and loose stools and was started on
broad-spectrum antibiotics and antifungals. One week later,
he developed rapidly progressive ascending areflexic
weakness of the limbs; within 24 hours, he had paralysis of
respiratory muscles necessitating emergency endotracheal
intubation and mechanical ventilation. His nerve conduction
study showed marked reduction of CMAPs from all upper and
lower limb nerves tested. None of the F waves was elicitable.
Conduction velocities and distal motor latencies were
relatively preserved. All the SNAPs were elicited normally.
Repetitive nerve stimulation from ulnar and facial nerves
did not result in any decremental response. He was started
on IVIg and he showed signs of improvement in the form of
voluntary movements of the limbs, on the fourth day.
However, he succumbed to sepsis.
Neither of the children had any known
family history of hereditary neuropathies or foot deformity.
The parents were evaluated retrospectively for evidence of
hereditary neuropathies and they were normal.
Discussion
We report two patients who developed GBS
during treatment for ALL. The pattern and evolution of the
neurological syndrome and electrodiagnostic features in both
children were consistent with AMAN variant of GBS [5]. The
CSF study was supportive of the diagnosis in the first child
but could not be repeated after the onset of polyneuropathy
in the second case because of severe thrombocytopenia and
coagulopathy.
Guillain-Barre syndrome is an acute
immune polyneuropathy and demyelinating and axonal subtypes
are described [1]. There are only very few reports of GBS in
children with ALL [2,3,6]. Out of the five cases so far
reported, three were from a single centre [3]. Autoimmune
disorders are known to occur in ALL [7,8]. Depletion of the
regulatory T cells which suppress auto-reactive T cells,
either resulting from ALL or intensive chemotherapy has been
postulated as the mechanism underlying immune
thrombocytopenia in ALL[7]; similar mechanisms may underlie
the genesis of acute immune neuropathies in ALL. The
immunological vulnerability of the peripheral nervous system
could be increased in lymphoproliferative disorders; known
infective triggers could precipitate an immune neuropathy in
this setting. The association between GBS and ALL could be
coincidental or causal. However, the occurrence of immune
neuropathy in immunocompromised children is interesting.
Improvement of GBS with immunotherapy (before remission of
ALL) is not unexpected as GBS is an autoimmune disorder, not
directly related to the hematologic malignancy.
An important consideration in children
with ALL developing neuropathy while on chemotherapy is
vincristine-induced neuropathy. But the clinical and
electrodiagnostic findings will be distinct for vincristine
induced neuropathy, [9] which is a toxic, "dying-back"
neuropathy with prominent sensory involvement [10].
Vincristine may also cause a fulminant neuropathy with
severe weakness in patients with Charcot-Marie-Tooth
disease; the clinical and electrophysiological features in
our cases were not supportive of this. Critical illness
polyneuropathy could be considered in critically ill ALL
patients; however, our patients did not satisfy the
definition for "critical illness" (no multi-organ failures /
mechanical ventilation) prior to onset of neuro-muscular
illness.
It has been recently suggested that GBS
in ALL is probably more common than expected[3]; a high
index of suspicion is needed for differentiation from other
neuropathies. Electrophysiological studies guide to the
correct diagnosis. The differentiation is important to
initiate timely immunomodulatory therapies for GBS and avoid
unnecessary withdrawal of vincristine, which could worsen
the outcome of ALL.
Contributors: BR and SK were
involved in review of literature and preparation of
manuscript. SC and KP prepared the final manuscript. All
were involved in management of the patients.
Funding: None; Competing interests:
None stated.
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