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CHEMOTHERAPY INDUCE ENCEPHALOPATHY AND NEUROPATHY IN A CHILD WILT
ACUTE LYMPHOBLASTIC LUKEMIA
Case report
Introduction:
Chemotherapy induced neurotoxicity (CIN)is the second most common side effect of
chemotherapy(1).The mechanism is still not well understood. The hallmark of CIN is usually
prominent sensory involvement.
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 (2,3). There
are only few reports of GBS in children with ALL (2).
However, the differentiation between these two entities is sometimes quiet difficult and is
important from the therapeutic point of view. We will present a case report where sever CIN
presented with normal sensory part associated with encephalopathy.
Case Presentation
Three years old girl was diagnosed at the age of ten months as infantile Acute Lymphoblastic
Leukemia (ALL).she was started on chemotherapy since that time and gained complete
remission with CNS negative disease. At week 81 of her chemotherapy course, she received IV
vincristine, 6MP and intrathecal methotrexate. Two days later, she presented to ED with low
back pain and fever followed by neck pain and stiffness. There was no history of diarrhea or
URTI.
CHEMOTHERAPY INDUCE ENCEPHALOPATHY AND NEUROPATHY IN A CHILD WILT
ACUTE LYMPHOBLASTIC LUKEMIA
Initial CSF study use normal including protein and cell count. CT brain and cerebrospinal fluid
were normal. Within one week, she developed ascending paralysis started from lower limbs then
involved upper limbs with areflexia and urinary retention.
MRI Spine was done and showed Smooth enhancement of the nerve roots at the level of
the cauda equina and mild leptomeningeal enhancement over the conus medullaris.
In addition, MRI Brain showed Mild ependymal enhancement noted in the brainstem
Repeated CSF showed high protein 736 mg/L, nerve conduction study showed sever axonal
neuropathy with normal sensory part so
IVIG 500mg/kg/day for 4 days without any
improvement.
Unfortunately, she was intubated because of respiratory muscle weakness and became very
weak, so second dose of IVIG was given .
she had Complete paralysis of upper and lower limbs without cough or gag so Plasma pharesis
was done without improvement. In addition, tracheostomy was done for prolonged intubation
and loss of airway reflexes.
She developed unique picture of encephalopathy in form of impaired communication to parents,
inattention and one attack of seizure. EEG showed diffuse Encephalopathy without epileptiform
discharges.
Repeated MRI brain showed diffuse
FLAIR (Fluid-attenuated inversion recovery) hyper
intensity involving the cerebellar cortex, bilateral par hippocampal, bilateral rectus gyrus
region with no corresponding enhancement or diffusion restriction abnormality. The
CHEMOTHERAPY INDUCE ENCEPHALOPATHY AND NEUROPATHY IN A CHILD WILT
ACUTE LYMPHOBLASTIC LUKEMIA
constellation of the findings is nonspecific which could be related to paraneoplastic
syndrome, sequelae of infectious process or could be related to chemotherapy.
She was connected to home ventilator and shifted to the pediatric floor
Figure 1
Figure 2
Discussion:
Chemotherapy induced neuropathy is usually manifested by prominent sensory symptoms as the
platinum class of alkylating agents or as in vincristine with sensorimotor Peripheral neuropathy,
mononeuropathy, cranial nerve palsy, autonomic neuropathy. Subacute myeloencephalopathy
with transient or permanent paraplegia/quadriplegia after intrathecal chemotherapy have been
reported (4)
A direct toxic effect of the intrathecal chemotherapy seems the most likely mechanism(4).
Anterior lumbosacral radiculopathy is also a type of neurologic complication associated with
intrathecal methotrexate treatment (5).
CHEMOTHERAPY INDUCE ENCEPHALOPATHY AND NEUROPATHY IN A CHILD WILT
ACUTE LYMPHOBLASTIC LUKEMIA
There was a report three children who developed progressive paraparesis after intrathecal
methotrexate administration followed by complete or partial recovery. EMG and NCS
demonstrated axonal neuropathy. Gadolinium enhancement of anterior lumbosacral spinal nerve
roots was demonstrated in all three patients, and an elevation of cerebrospinal fluid protein.
There was no encephalopathy and they recover(5). However our patient had encephalopathy
without impressive MRI finding and she didn’t recover with significant residual quadriplegia.
Another case report showed a six year old who developed progressive dense quadriplegia and he
did not have any sensory symptoms. His NCS was suggestive of a motor axonopathic
polyradiculoneuropathy(6). After a course of IVIG ,he had normal power of all the limbs and
was ambulant normally
Unfortunately our patient didn’t improve and she became bedridden with significant residual
dysfunctional neurological impairment .
So we believe that she had a sever chemotherapy induced peripheral neuropathy with central
neurotoxicity may be related to high doses of vincristin and methotrexate.
Vincristin Neurotoxicity is dose related and cumulative with repeated dosage such that the drug
therapy has to be stopped after a cumulative dose of 30 to 50 mg. The neurotoxicity is usually
reversible on interruption of the therapy, but the recovery is slow and takes several months(7).
Our patient received a total vincristin dose of 53 mg/m2 which exceed the upper limit dose and
total intrathecal methotrexate dose of 220 mg/m2 in addition to IV methotrexate 1320 mg/m2
CHEMOTHERAPY INDUCE ENCEPHALOPATHY AND NEUROPATHY IN A CHILD WILT
ACUTE LYMPHOBLASTIC LUKEMIA
Conclusion
Chemotherapy side effects could be so debilitating and harmful and sometimes no single agent
can be pointed.
We reported a unique association between sever neuropathy and encephalopathy in acute
lymphoblastic leukemia with sever axonopathy and unremarkable MRI.
References
1. Franconi G, Manni L, Schroder S, Marchetti P and Robinson N. A Systematic Review of
Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral
Neuropathy, Evidence-Based Complementary and Alternative Medicine. 2013; Article ID
516916, 7 pages.
2. Aral YZ, Gursel T, Ozturk G, Serdaroglu A. Guillain-Barre´ syndrome in a child with
acute lymphoblastic leukemia. Pediatr Hematol Oncol. 2001;18:343-6.
3. Brigo F, Balter R, Marradi P, Ferlisi M, Zaccaron A, Fiaschi A, et al. Vincristine-related
neuropathy versus acute inflammatory demyelinating polyradiculoneuropathy in children
with acute lymphoblastic leukemia. J Child Neurol. 2012;27:867-74.
4. Garcia-Tena J, Lopez J, Servicio de Neuropediatría, Hospital †Correspondence: Josep
Ferrís, Unidad de Oncología Pediátrica, Hospital Infantil “La Fe,” Avda de Campanar,
21, 46009, Valencia, España. Intrathecal chemo related myeloencephalopathy in a young
child
with
ALL.
Ped
Hematology-Oncology
Journal
1995;
5. Koh S, MDa, Nelson M Jr, MDb, Kovanlikaya A, MDb, Chen L. Anterior lumbosacral
radiculopathy after intrathecal methotrexate treatment, Pediatric Neurology Journal
1999.
6. Rajeswari B, Krishnan S, Sarada C, Kusumakumary P. Guillain-Barré Syndrome with
Acute Lymphoblastic Leukemia. From Division of Pediatric Oncology, Regional Cancer
Centre; and *Department of Neurology, Sree Chitra Tirunal Institute for Medical
Sciences and Technology, Thiruvananthapuram, India. Indian pediatrics Aug 2013
7. Legha SS. Vincristine neurotoxicity. Pathophysiology and management. Med
Toxocology ,1986 Nov-Dec;1(6):421-7.
CHEMOTHERAPY INDUCE ENCEPHALOPATHY AND NEUROPATHY IN A CHILD WILT
ACUTE LYMPHOBLASTIC LUKEMIA
Key Words:
Chemotherapy encephalopathy; neuropathy; acute lymphoblastic lukemia