Pediatr Blood Cancer 2010;55:12341235

BRIEF REPORT
Acute Onset Flaccid Quadriparesis in Pediatric Non-Hodgkin Lymphoma:
Vincristine Induced or GuillainBarre Syndrome?
Ankur Bahl, MD,1 Biswaroop Chakrabarty, MD,2 Sheffali Gulati, MD,2 K.N. Vykunta Raju, MD,2 Ali Raja, MD,3
and Sameer Bakhshi, MD1 *
Immunological involvement of peripheral nervous system in nonHodgkin lymphoma (NHL) is very rare and it may be difcult to
differentiate it from vincristine-induced neuropathy. We report clinical and electrophysiological ndings of an 8-year-old male with NHL
who developed acute onset fulminant motor sensory autonomic neuropathy during induction chemotherapy which included vincristine.

Characteristic clinical picture and nerve conduction studies favored

GuillainBarre syndrome. The patient improved rapidly with intravenous immunoglobulin and supportive care. It is possible that an
immune mechanism damaged the peripheral nervous system in the
patient without ruling out the adverse effects of vinca alkaloids. Pediatr Blood Cancer. 2010;55:12341235. 2010 Wiley-Liss, Inc.

Key words: accid quadriparesis; GuillainBarre syndrome; non-Hodgkin lymphoma; vincristine

INTRODUCTION
Complications involving the peripheral nervous system (PNS)
occur in approximately 5% of patients with non-Hodgkin lymphoma (NHL) [1]. Medication-induced toxicity represents a major
cause of neuropathy. Vinca alkaloids, widely used in the treatment
of lymphoma, commonly cause distal axonal degeneration in a
dose-related fashion by binding to tubulin and thereby blocking its
polymerization into microtubules [2]. Infiltration of nerve roots or
peripheral nerves mostly occurs in NHL, whereas the incidence of
immunological disorders of the PNS, such as GuillainBarre syndrome (GBS), is usually associated with Hodgkin lymphoma [3]. We
report a child with newly diagnosed bilateral renal NHL who developed an acute onset fulminant axonal motor sensory quadriplegic
neuropathy during a vincristine-containing induction chemotherapy
regimen.

CASE REPORT
An 8-year-old male was admitted with 6 weeks history of fever
and progressive abdominal distension. Computed tomography scan
showed bilateral renal masses, biopsy from which showed features
of B-NHL. Complete blood counts, renal and liver function tests
were normal; serum lactate dehydrogenase was 857 U/ml (normal
levels <450 U/ml). His bone marrow and cerebrospinal fluid (CSF)
were not involved with malignant cells. Thus, final diagnosis was St.
Jude stage III B-NHL. Patient was started on chemotherapy as per
BFM-90 protocol [4]. After prephase therapy with dexamethasone
and cyclophosphamide, the first cycle of chemotherapy was administered which included vincristine, dexamethasone, ifosphamide,
cytosine arabinoside, and etoposide; high-dose methotrexate was
not given in this cycle. After 7 days of this therapy, the mass was
not palpable.
On day 11 of chemotherapy, patient developed acute onset flaccid motor sensory quadriparesis. The power of both upper and lower
limbs was 2/5 (proximal weakness more than distal) and all deep
tendon reflexes were absent. Cranial nerve examination was normal except for an absent gag reflex. The heart rate was ranging
from 160 to 180/min and blood pressure was 180/110 mmHg. In
view of poor respiratory effort, he was put on mechanical ventilation. Serum potassium and blood glucose levels were normal.

2010 Wiley-Liss, Inc.

DOI 10.1002/pbc.22684
Published online 11 June 2010 in Wiley Online Library
(wileyonlinelibrary.com).

CSF was acellular with protein 20 mg/dl (normal 1858 mg/dl) and
sugar 90 mg/dl (normal 5080 mg/dl). Standard nerve conduction
studies (NCS) were suggestive of axonal motor sensory neuropathy involving both upper and lower extremities with no evidence of
demyelination. With the clinical evidence of acute onset motor sensory quadriparesis, autonomic neuropathy, and characteristic NCS
findings, a diagnosis of GBS was considered. Investigations for possible etiology of GBS included absence of IgM and IgG antibodies
to ganglioside GM1; negative serology and stool culture for Campylobacter jejuni; and absence of amplification of Cytomegalovirus by
polymerase chain reaction.
Intravenous immunoglobulin (IVIg) at a dose of 400 mg/kg/day
for 5 days was administered within 24 hr of the onset of this
acute illness; invasive ventilation and passive physiotherapy was
given as supportive therapy. During the course of this critical illness he was neutropenic and developed febrile neutropenia and
ventilator-associated pneumonia. He was managed with intravenous antibiotics, antifungals, and growth factors. Patient showed
improvement in power in both upper and lower extremities with
appearance of gag reflex on day 6 of IVIg therapy and was weaned
off from ventilator on day 9 of therapy. He became ambulatory by
day 13 of the onset of quadriparesis but sensory symptoms persisted. Repeat CSF evaluation 1 week after onset of the neuropathy
was also normal. NCS done at week 3 revealed residual axonal
motor neuropathy with some improvement; however, there was no
improvement in axonal sensory neuropathy. The second cycle of
chemotherapy was initiated as per protocol, but vincristine was
omitted from the protocol (to prevent further neurotoxicity). NCS

1
Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer
Hospital, All India Institute of Medical Sciences, New Delhi, India;
2
Department of Pediatric Neurology, All Institute of Medical Sciences,
New Delhi, India; 3 Department of Anesthesia, All Institute of Medical
Sciences, New Delhi, India

Conflict of interest: Nothing to declare.

*Correspondence to: Dr. Sameer Bakhshi, Associate Professor of Pediatric Oncology, Department of Medical Oncology, Dr. B.R.A. Institute
Rotary Cancer Hospital, All India Institute of Medical Sciences, New
Delhi 110029, India. E-mail: sambakh@hotmail.com
Received 6 April 2010; Accepted 11 May 2010

NHL With Paralysis Due To GuillainBarre Syndrome

repeated further at week 8 revealed complete resolution of the sensorimotor neuropathy. Patient has been in complete remission after
three cycles of chemotherapy.

DISCUSSION
Functionally disabling peripheral neuropathies of diverse etiologies may complicate the course of malignant lymphoid
proliferations [5]. Direct lymphomatous infiltration of nerves,
deposition of a paraprotein, and immune dysfunction causing paraneoplastic disease or GBS have been described as mechanisms
of peripheral neuropathy in NHL based on morphological and
immunological findings [6]. Direct lymphomatous infiltration of
nerve is unlikely in our patient as there were no signs and symptoms
of nerve infiltration at diagnosis; moreover, the patient was in clinical
remission on day 7 of the chemotherapy. Paraneoplastic neuropathy usually occurs in Hodgkin lymphoma and frequently presents
as a subacute sensory neuropathy. Our patient had fulminant acute
onset motor sensory neuropathy with autonomic dysfunction after
initiating chemotherapy which is unusual for a paraneoplastic neuropathy. However, no known antineuronal antibodies were tested in
our patient to refute the diagnosis of paraneoplastic neuropathy.
A distal sensorimotor dying-back type of neuropathy is the typical clinical presentation occurring weeks to months after exposure
to vinca alkaloids [2]. In patients who are treated with vincristine,
dose-dependent relationship with neuropathy is observed; usually
it occurs at a cumulative dose of 5 mg for sensory symptoms and
30 mg for frank motor symptoms [7]. Motor sensory neuropathy at
lower dose of at least 8 mg has been described recently [8], but it
usually occurs in the presence of preexisting neuropathies particularly hereditary neuropathy. Severe paralyses have been reported
even at a dose as low as 2 mg in CharcotMarieTooth disease type
1 [9]. However, in our patient no signs of a preexisting neuropathy
were evident on clinical examination and his past medical history
was unremarkable. The rapidity and severity of the quadriparesis
with autonomic features in our patient following the first dose of
vincristine and also its rapid recovery is against the etiology of
vincristine-induced acute sensory motor axonal neuropathy.
The clinical presentation of our patient with acute onset flaccid
quadriparesis (proximal more than distal) with autonomic neuropathy and cranial nerve palsy was suggestive of GBS. Rapid clinical
recovery with IVIg administration and persistent NCS finding
further strengthen our belief. However, CSF protein levels were
normal on two occasions and no prodormal viral illness prior to
this catastrophic episode was observed. GBS is usually associated
with elevated CSF protein, but in 10% of the cases, it may be
normal [10].
GBS in the context of NHL treatment with vincristine has been
rarely observed [9,11,12]. Similar to our case, Wanschitz et al. [13]
reported acute axonal motor sensory quadriplegia after administration of a total cumulative dose of 4 mg vincristine in a case of
Burkitt-like lymphoma; this patient had elevated CSF protein and
expired within 5 months due to sepsis. Gonzalez Perez et al. [14]
reported a case of acute lymphoblastic leukemia who after initiation
of treatment with vincristine (total dose 4 mg) developed a fulmi-

Pediatr Blood Cancer DOI 10.1002/pbc

1235

nant polyradiculoneuropathy resembling an axonal variant of GBS

similar to our patient; this patient had normal CSF protein levels but
despite daily intensive rehabilitation he became wheelchair-bound
and died within 4 months due to pneumonia. Previously, IVIg has
also been used to treat vincristine-induced axonal neuropathy in
hematological malignancies [15].
In conclusion, the present case reflects the various challenges
faced to narrow down the differential diagnoses of flaccid quadriplegia in a case of NHL undergoing chemotherapy. Clinically, a
diagnosis of GBS was made in the patient and he improved with
IVIg. However, grade 4 toxicity due to vincristine cannot entirely
be ruled out; therefore, vincristine was not used further in subsequent
chemotherapy cycles.

REFERENCES
1. Hughes RA, Britton T, Richards M. Effects of lymphoma on the
peripheral nervous system. J R Soc Med 1994;87:526530.
2. Peltier AC, Russell JW. Recent advances in drug-induced neuropathies. Curr Opin Neurol 2002;15:633638.
3. Kelly JJ, Karcher DS. Lymphoma and peripheral neuropathy: A
clinical review. Muscle Nerve 2005;31:301313.
4. Seidemann K, Tiemann M, Schrappe M, et al. Short-pulse
B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: A report of
the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood
2001;97:36993706.
5. Vallat JM, De Mascarel HA, Bordessoule D, et al. Non-Hodgkin
malignant lymphomas and peripheral neuropathies13 cases.
Brain 1995;118:12331245.
6. Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol 2002;249:917.
7. Casey EB, Jellife AM, Le Quesne PM, et al. Vincristine neuropathy.
Clinical and electrophysiological observations. Brain 1973;96:69
86.
8. Verstappen CC, Koeppen S, Heimans JJ, et al. Dose-related vincristine induced peripheral neuropathy with unexpected off-therapy
worsening. Neurology 2005;64:10761077.
9. Moudgil SS, Riggs JE. Fulminant peripheral neuropathy with
severe quadriparesis associated with vincristine therapy. Ann Pharmacother 2000;34:11361138.
10. Segurado OG, Kruger H, Mertens HG. Clinical significance of
serum and CSF findings in the GuillainBarre syndrome and related
disorders. J Neurol 1986;233:202208.
11. Norman M, Elinder G, Finkel Y. Vincristine neuropathy and a
GuillainBarresyndrome: A case with acute lymphatic leukemia
and quadriparesis. Eur J Haematol 1987;39:7576.
12. Re D, Schwenk A, Hegener P, et al. GuillainBarre syndrome in a
patient with non-Hodgkins lymphoma. Ann Oncol 2000;11:217
220.
13. Wanschitz J, Dichtl W, Budka H, et al. Acute motor and sensory axonal neuropathy in Burkitt-like lymphoma. Muscle Nerve
2006;34:494498.
14. Gonzalez Perez P, Serrano-Pozo A, Franco-Macas E, et al.
Vincristine-induced acute neurotoxicity versus GuillainBarre syndrome: A diagnostic dilemma. Eur J Neurol 2007;14:826828.
15. Yusuf ZA, Turkiz G, Gulyuz O, et al. GuillainBarre syndrome in
a child with acute lymphoblastic leukemia. Pediatr Hematol Oncol
2001;18:343346.