Pediatr Blood Cancer 2007;48:233–237

BRIEF REPORTIntraspinal and Intracranial Hemorrhage

After Lumbar Puncture

Anselm C.W. Lee, FHKAM,1* Yu Lau, MB, BS,1 C.H. Li, FHKAM,1 Y.C. Wong, FHKAM,2

and Alan K.S. Chiang, FHKAM3

INTRODUCTION

Lumbar puncture (LP) is a common pediatric diagnostic

procedure. In pediatric oncology, LP is also used therapeu-

tically in which chemotherapy is instilled into the cere-

brospinal fluid (CSF) as a treatment directed to the central

nervous system. Direct trauma to the intraspinal structures,

bleeding, and chemical irritation are occasionally reported.

In the presence of thrombocytopenia, prophylactic platelet

transfusion has been recommended before an LP [1,2]. The

numerical level of platelet count below which platelet

transfusion has to be administered remains a matter of

controversy [3]. Our experience of extra-axial bleeding

complications in four children are presented (Table I).

CASE REPORTS

Case A

A 13-year-old boy who relapsed with B-cell acute

lymphoblastic leukemia received the first LP on Day 1 of

treatment under platelet transfusion cover, with injection of

methotrexate, cytarabine, and hydrocortisone intrathecally.

The platelet count immediately before the procedure was

46� 109/L. The procedure was accomplished uneventfully

and the patient did not have any complaint of backache or

symptoms of radiculopathy. The CSF contained leukocytes

of 10� 109/L and there were no erythrocytes. The patient

was managed as positive for central nervous system disease,

and he had the second LP 2 days later under prophylactic

platelet transfusion. Repeated attempts at multiple spinal

levels only yielded frank blood when needle position was

determined by the sense of change in resistance. A magnetic

resonance imaging (MRI) showed the presence of an

extradural collection, extending from the level of T12 to L5

(Fig. 1A). A drop in the hemoglobin from 8.1 to 5.6 g/dL was

noted in the 48 hr following the first LP. An epidural

hematoma, probably occurring after the first LP, was

diagnosed. It was asymptomatic but it precluded successful

LP in the usual manner. Subsequent LP had to be carried out

by inserting the spinal needle to a measured depth of 3.7 cm,

whichwas the distance of the CSF space to the skinmeasured

by MRI. The scheduled treatment was continued success-

fully and he remained well in second complete remission for

more than 6 years.

Case B

A 4-year-old girl with newly diagnosed B-precursor acute

lymphoblastic leukemia received LP and intrathecal metho-

trexate on the first day of treatment. The procedure was

accomplished successfully at a platelet count of 159� 109/L.

The CSF revealed red cell and white cell counts of <1 and

2� 109/L, respectively, without malignant cells. About 24 hr

later, she started to complain of low back pain around the

site of LP, and refused to lie flat or ambulate. Bladder and

bowel functionwas not affected. Examination of the patient’s

back was unrevealing, and the neurological functions of

the lower limbs were preserved. Plain radiographs of the

lumbosacral spine and the hips did not show any pathology.

As her symptoms persisted in the next 24 hr with analgesic

treatment, MRI was obtained. An extradural collection

extending from T8 to L5 vertebral levels with thecal sac

Two cases of spinal epidural hematoma and two cases ofintracranial subdural hematoma after lumbar puncture (LP) arereported in children receiving chemotherapy for acute lymphoblasticleukemia and non-Hodgkin lymphoma. The bleeding was asympto-matic but interfered with treatment in one case, and caused eithersevere backache or headache but no neurological deficit in the otherthree patients. The platelet counts were 8 and 46� 109/L in two

patients and were normal in the other patients at the time of LP. Allrecovered without surgical treatment. There is an inherent, albeituncommon, risk of bleeding into the central nervous system asso-ciated with LP in children with cancer and should be distinguishedfrom postdural puncture headache (PDPH). Thrombocytopenia is notalways an accompanying factor. Pediatr Blood Cancer 2007;48:233–237. � 2005 Wiley-Liss, Inc.

Key words: acute lymphoblastic leukemia; intraspinal hemorrhage; lumbar puncture; non-Hodgkin lymphoma; postdural punctureheadache; subdural hematoma

� 2005 Wiley-Liss, Inc.DOI 10.1002/pbc.20551

——————1Department of Paediatrics & Adolescent Medicine, Tuen Mun

Hospital, New Territories, Hong Kong, China; 2Department of

Diagnostic Radiology, Tuen Mun Hospital, New Territories, Hong

Kong, China; 3Department of Paediatrics & Adolescent Medicine, the

University of Hong Kong, Queen Mary Hospital, Hong Kong, China

*Correspondence to: Dr. Anselm C.W. Lee, Department of Paediatrics

& Adolescent Medicine, Tuen Mun Hospital, New Territories, Hong

Kong, China. E-mail: aclee@graduate.hku.hk

Received 6 April 2005; Accepted 28 June 2005

displacement was seen (Fig. 1B). A spinal epidural

hematoma was diagnosed and she recovered with bed rest

and analgesics in the next 72 hr.

Case C

An 11-year-old girl with B-precursor acute lymphoblastic

leukemia received an intrathecal injection of methotrexate

during the re-induction phase 9 months into her treatment

protocol. The platelet count obtained before the procedure

was 8� 109/L, but platelet transfusionwas omitted. About an

hour later, the patient complained of frontal headache and

pain in her eyes. The neurological and fundoscopic

examinations did not reveal any abnormal findings. Her

symptoms persisted despite analgesics. CT scan performed

24 hr after the procedure showed the presence of subdural

blood over the tentorium and the posterior interhemispheric

fissure (Fig. 1C). The headache gradually resolved over the

next week, while the intracranial bleeding disappeared on

subsequent imaging.

Case D

A 9-year-old boy with stage III diffuse large B cell

lymphoma involving the cervical, mediastinal, and retro-

peritoneal nodes underwent LP and intrathecal chemother-

apy on Day 8 of his treatment. The platelet count was

250� 109/L but the LP was traumatic. The child complained

of a persistent frontal headache afterwards that did not

respond to supportive care and analgesic. MRI of the brain

performed at about 48 hr after the procedure showed the

presence of acute subdural hematoma at the right ambient

cistern, the right falx cerebelli, the tentorium, and the falx

cerebri (Fig. 1D). Chemotherapy was continued, with

omission of the next intrathecal injection on Day 13 of

treatment. His condition improved spontaneously and the

subdural collection resolved on subsequent imaging.

DISCUSSION

LP is a common procedure in pediatric oncology,

especially in children with hematologic malignancies.

Complications following LP include headaches and back-

aches [4], cerebellar herniation in the presence of increased

intracranial pressure [5], trauma to the conus medullaris [6],

bleeding [7], iatrogenic meningitis [8], and implantation

dermoid [9]. Most of these complications are related to

inappropriate techniques or risk assessment, and are not

specific to children with cancer. Hemorrhagic complications,

however, are of particular concern.

Significant bleeding after LP may occur either in-

traspinally or intracranially. Intraspinal bleeding may be

epidural, subdural, or subarachnoid [10]. The clinical signs

of the various forms of intraspinal bleeding are indistin-

guishable clinically, and include backaches, radiculopathy,TABLEI.

ClinicalSummary

oftheCases

Case

Sex/age

Diagnosis

Tim

efrom

diagnosis

Platelet�

109/L

Platelettransfusion

before

LP

PT/

APTT

RBC

inCSF

Hem

orrhagic

complicationsb

Sedationused

Operatorexperience

AM/13

ALL

1day

23a

Yes

N0

Epidural,spinal

Ketam

ineþmidazolam

Attendingphysician

BF/4

ALL

1day

159

No

N0

Epidural,spinal

Ketam

ineþmidazolam

Resident

CF/11

ALL

9months

8No

ND

TT

Subdural,cranial

Ketam

ineþmidazolam

Attendingphysician

DM/9

NHL

8days

250

No

NTT

Subdural,cranial

Ketam

ineþmidazolam

Resident

ALL,acutelymphoblasticleukem

ia;A

PTT,activated

partialthromboplastintime;CSF,cerebrospinalfluid;N

,norm

al;N

D,notdone;NHL,non-H

odgkinlymphoma;PT,prothrombintime;RBC,red

bloodcells;TT,traumatictap.

Alllumbar

punctures(LP)wereperform

edwithgauge22spinalneedles.Noneofthepatientshad

anysignificantderangem

entin

liver

orrenalfunction,orpersonalorfamilyhistory

ofbleeding

tendency

priorto

thediagnosisofprimarydisease.

aTheposttransfusionplateletcountwas

46�109/L.

bAllhem

orrhagiccomplicationsresolved

spontaneouslywithoutsurgicalintervention.

Pediatr Blood Cancer DOI 10.1002/pbc

234 Lee et al.

and signs of cord compression depending on the level of

involvement in the spine and the rapidity of the clot forma-

tion [10]. Edelson et al. [11] and Dunn et al. [12] reported

nine cases of spinal subdural hematoma after LP in

thrombocytopenic patients, four of whom presented with

acute paraplegia. Reversible paraplegia due to spinal

subarachnoid hematoma has also been reported in a 25-

year-old leukemic patient after LP [13]. Among these five

cases of intradural bleeding leading to acute paraplegia in the

literature, three patients were suffering from acute leukemia

and the bleeding occurred after the first LP. A case of

spontaneous bleeding has been noted in a 26-year-old man

with relapsing chronic myeloid leukemia and high platelet

counts [14].

The optimal management of intraspinal hemorrhages is

unclear, but surgical intervention with laminectomy or

evacuation of the blood clot is recommended in the presence

of spinal cord compression [10]. On the other hand,

conservative management may be all that is required in the

absence of signs of cord dysfunction [15] like the cases that

are presented in this report. Successful outcome without

surgery has also been noted in spontaneous intraspinal

hemorrhage associated with moderate hemophilia A [16].

The occurrence of intracranial subdural hematoma is

closely related to the syndrome of postdural puncture

headache (PDPH). PDPH occurs in 2%–40% of adult

patients after LP, and is closely associated with the size of

the puncturing needle and the subsequent CSF leak from the

Fig. 1. Fast-spin echo T2-weigted sagittal image of lumbar spine in Case A (A) and axial image of lumbar spine in Case B (B), showinghyperintense extradural collection in the posterior extradural space that displaces and compresses on the thecal sac. Non-contrast axial image of the

brain in Case C (C) showing hyperdense acute subdural hematoma in the posterior interhemisphere fissure. Spin echo T1-weighted sagittal image of

the brain in Case D (D) showing hyperintense, subdural hematoma including the tentorium and posterior falx cerebri.

Pediatr Blood Cancer DOI 10.1002/pbc

CNS Hemorrhage After LP 235

defect in the dura mater [17]. The typical case presents with

headache in the frontal or occipital areas and backachewithin

3 days of the procedures; symptoms are most pronounced

in the upright posture or during head movements. Other

associated symptoms include nausea, vomiting, hearing loss,

tinnitus, vertigo, and dizziness. The headache is self-limiting

in the majority of cases and usually subsides within a week,

but it may last for months or years in occasional patients.

Analgesics may be helpful but seldom ameliorate the

symptoms completely. The loss of CSF is believed to evoke

an engorgement of the epidural venous plexus in a com-

pensatory manner [17]. Subdural hematoma occurs when

these bridging dural veins are ruptured as a result of the

change in brain volumes. The complication has been

commonly observed after CSF shunting procedures [18],

but it has also been reported occasionally in patients after LP

[19] or lumbar myelography [20]. Thrombocytopenia does

not appear to be a necessary factor, but it may be contributory

[21]. Hence, a complaint of headache after LP should be

handled with caution. CT of the brain or MRI of the spinal

region should be carried outwhen bleeding complications are

suspected [10].

Intracerebral and subarachnoid hemorrhages have also

been reported after LP in oncology patients [22]. The risk of

subdural hematoma appears to be highest in the presence of

prolonged thrombocytopenia associated with bone marrow

transplantation [7]. Among 19 transplant recipients who

complained of PDPH, 14 (74%) were found to have a

clinically significant subdural hematoma. Once diagnosed,

the affected patient should be put under close observation

with strict bed rest and pain treatment. Coagulopathy, if

present, should be corrected and our practice is to maintain

the patient’s platelet count at levels above 50� 109/L.

Surgical treatment may be indicated if the bleeding becomes

life threatening.

Most recommendations specify the use of prophylactic

platelet transfusion before LP in thrombocytopenic patients,

but the trigger level of platelet counts under such circum-

stances is controversial [3,23]. All pediatric oncology

center’s in Hong Kong are using a platelet count of

50� 109/L below which platelet transfusion is given prior

to LP, which is in line with other recommendations [1,2].

There are few data to support the scientific basis for both

these guidelines. Retrospective studies, however, showed

that LP was a safe procedure in patients with platelet counts

as low as 10� 109/Lwithout blood product support [3]. In the

largest series reported to date, no serious complications were

observed among 941 procedures done with platelet counts of

50� 109/L or less, including 29 children whose platelet

counts were less than 10� 109/L [24]. In view of the lack of

significant complications of LP in thrombocytopenic patients

and the risks and costs of administering platelet concentrates

[25], there are recent suggestions to raise the threshold by

transfusing platelets at a lower platelet trigger. Our report

illustrated the inherent risks of central nervous system

bleeding associated with LP and thrombocytopenia did not

seem to be the causative factor in three of our four cases of

bleeding. Coagulation testing should also be obtained

especially when patients are treated with drugs that may

affect the liver function.

In summary, intraspinal and intracranial hematoma may

complicate LP in children with cancer. As our cases occurred

during the early phase of treatment, it is possible that this

period represents a time of higher risk for these complica-

tions. The role of thrombocytopenia in the pathogenesis

of LP-associated central nervous system bleeding cannot

be clearly defined, but prophylactic transfusion does not

appear to be always effective in protecting against such

complications.

REFERENCES

1. British Committee for Standards in Haematology. Guidelines

for the use of platelet transfusions. Br J Haematol 2003;122:

10–23.

2. Schiffer CA, Anderson KC, Bennett CL, et al. Platelet transfusion

for patients with cancer: Clinical practice guidelines of the

American Society of Clinical Oncology. J Clin Oncol 2001;19:

1519–1538.

3. Feusner J. Platelet transfusion trigger for lumbar puncture. Pediatr

Blood Cancer 2005;43:793.

4. Ebinger F, Kosel C, Pietz J, et al. Headache and backache after

lumbar puncture in children and adolescents: A prospective study.

Pediatrics 2004;113:1588–1592.

5. Oliver WJ, Shope TC, Kuhns LR. Fatal lumbar puncture: Fact

versus fiction—an approach to a clinical dilemma. Pediatrics

2003;112:e174–e176.

6. Tubbs RS, Smyth MD, Wellons JC, et al. Intramedullary hemor-

rhage in a neonate after lumbar puncture resulting in paraplegia: A

case report. Pediatrics 2004;113:1403–1405.

7. Colosimo M, McCarthy N, Jayasinghe R, et al. Diagnosis

and management of subdural haematoma complicating bone

marrow transplantation. Bone Marrow Transplant 2000;25:549–

552.

8. Pandian JD, Sarada C, Radhakrishnan VV, et al. Iatrogenic

meningitis after lumbar puncture—a preventable health hazard.

J Hosp Infect 2004;56:119–124.

9. Ziv ET, McComb JG, Krieger MD, et al. Iatrogenic intraspinal

epidermoid tumor. Spine 2003;29:E15–E18.

10. Watts C, Ryken TC. Intraspinal hemorrhage from idiopathic or

structural causes. In: Grossman RG, Loftus CM, editors. Principles

of neurosurgery. Philadelphia: Lippincott-Raven Publishers; 1999;

pp 627–638.

11. Edelson RN, Chernik NL, Posner JB. Spinal subdural hemato-

mas complicating lumbar puncture. Arch Neurol 1974;31:134–

137.

12. Dunn D, Dhopeah V, Mobini J. Spinal subdural hematoma: A

possible hazard of lumbar puncture in an alcoholic. JAMA 1979;

241:1712–1713.

13. Blade J, Gaston F, Moniserrai E, et al. Spinal subarachnoid

hematoma after lumbar puncture causing reversible paraplegia in

acute leukemia. J Neurosurg 1983;58:438–439.

14. Banerjee R, Stanley J, Palumbo M. Spinal epidural hematoma

induced by leukemia. Orthopedics 2004;27:864–866.

15. Groen RJM. Non-operative treatment of spontaneous spinal

epidural hematomas: A review of the literature and a comparison

with operative cases. Acta Neurochir 2004;146:103–110.

Pediatr Blood Cancer DOI 10.1002/pbc

236 Lee et al.

16. Irwin SL, Attia MW. Atraumatic spinal epidural hematoma

in an infant with hemophilia A. Pediatr Emerg Care 2001;17:

40–41.

17. Turnbull DK, Shepherd DB. Post-dural puncture headache:

Pathogenesis, prevention and treatment. Br J Anaesth 2003;91:

718–729.

18. Wiesmann M, Mayer TE. Intracranial bleeding rates associated

with two methods of external ventricular drainage. J Clin Neurosci

2001;8:125–128.

19. Samdiani A, Garonzik IM, Zahos P. Subdural hematoma after

diagnostic lumbar puncture. Am J Emerg Med 2004;22:316–

317.

20. Suess O, Stendel R, Baur S, et al. Intracranial haemorrhage fol-

lowing lumbar myelography: Case report and review of the

literature. Neuroradiology 2000;42:211–214.

21. Ezri T, Abouleish E, Lee C, et al. Intracranial subdural hematoma

following dural puncture in a parturient with HELLP syndrome.

Can J Anesth 2002;49:820–823.

22. Alexopoulou A, Dourakis SP, Georgousi KK, et al. Intracerebral

hematoma following intrathecal administration of methotrexate in

a patient with non-Hodgkin’s lymphoma. Am J Hematol 2005;

78:159–160.

23. ContrerasM. Consensus conference on platelet transfusion: 27 and

28 November 1997: Final statement. Leukemia 1998;12:1330–

1331.

24. Howard SC, Gajjar A, Ribeiro RC, et al. Safety of lumbar puncture

for children with acute lymphoblastic leukemia and thrombocyto-

penia. JAMA 2000;284:2222–2224.

25. Heal JM, Blumberg N. Optimizing platelet transfusion therapy.

Blood Rev 2004;18:149–165.

Pediatr Blood Cancer DOI 10.1002/pbc

CNS Hemorrhage After LP 237