Dural Sinus Occlusion in Leukemia

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Dural

Sinus

Occlusion

in Leukemia

Ronald B. David, M.D.,

M. Gary Hadfield,

M.D.,

Frederick

S. Vines, M.D.,

and Harold M. Maurer, M.D.

From the Departments of Pediatrics, Radiology. and Pathology, Medical College of Virginia, Health Sciences Dicision of Virginia Commonwealth University, Richmond

ABSTRACT. The case of a 7-year-old child with acute lymphocytic leukemia who, while in relapse, developed a superior sagittal sinus thrombosis is documented by angiog-raphy and post-mortem examination. Review of the litera-ture suggests that cerebral spinal fluid (CSF) pleocytosis which usually accompanies the arachnoid infiltration of central nervous system (CNS) leukemia may be absent in some patients as in this case. In the absence of CSF pleocytosis, cerebral venous sinus thrombosis may mimic the other signs and symptoms of CNS leukemia and conse-quently may be a more frequent complication of acute leukemia than is presently appreciated. Therapy directed to the CSF axis generally would not under these circumstances be appropriate. Pediatrics, 56:793-796, 1975, CNS LEUKEMIA,

DURAL SINUS THROMBOSIS.

Central

nervous

system

(CNS)

leukemia

is

a

frequent

complication

of acute

leukemia

in

child-hood.

Stasis

and

impaction

of leukemic

cells

may

lead

to

micro-infarcts

and

hemorrhage.’

Indeed,

hemorrhage

is

typically

massive

and

fatal

in

blastic

crises

where

the

peripheral

white

cell

count

may

be

above

300,000/sq

mm.

In

addition

to

tumor

within

vessels,

infiltration

of

the

lep-tomeninges

by primitive

white

cells

may

occur

in

30%

of cases

of acute

leukemia,3

a fact

which

cor-relates

well

with

the

clinical

finding

that

a

signif-icant

number

of leukemic

patients

present

with

signs

of meningeal

irritation.4

Infiltration

of nerve

roots

is

also

frequent5

and

infiltration

of

brain

parenchyma

is not

uncommon’

but

infiltration

of

the

dura

is rarely

recorded.6

In

many

instances,

however,

we

feel

that

dural

involvement

may

have

been

overlooked

since

the

dura

mater

may

not

be

generally

as

well

studied

as the

brain

at

autopsy.

CASE REPORT

The patient was a 7-year-old boy who was admitted for evaluation of protracted vomiting and severe headache 3#{189} years after a diagnosis of acute lymphocytic leukemia was established. Prior to this admission he had been treated with a variety of antileukemic agents, including prednisone, vincristine, methotrexate, 6-mercaptopurine, and cyclophos-phamide. During this period, he had had several occurrences of typical CNS leukemia for which he was treated with intrathecally administered methotrexate. In the five weeks prior to this admission the patient had been in hematologic relapse. For this he received prednisone daily and intra-venous vincristine weekly. Two days prior to admission he was evaluated for a complaint of severe headache of five days’ duration. At this time his funduscopic examination was normal. A lumbar puncture revealed cerebral spinal fluid

(CSF) protein of 41 mg/100 ml and no cells. CSF manomet-rics were not performed. Since it was assumed that his headache was due to recurrent CNS disease, he was given a course of intrathecally administered cytosine arabinoside, and treatment was initiated with dexamethasone 4 mg orally three times a day.

On the day of admission the patient was awakened by an extraordinarily severe headache. Admission physical exami-nation revealed a cushingoid child with a pulse rate of 41 beats per minute, blood pressure of 140/80, and normal temperature. On neurological examination the cranial nerves were intact with the exception of blurred disc margins bilaterally, suggesting early papilledema. Deep tendon reflexes were equal and symmetrically hypoactive. Babinski sign was present bilaterally. Results of the remainder of the physical examination were within normal limits.

Pertinent laboratory data included a hemoglobin of 14.0 gm/100 ml, a white blood cell count of 13,000/cu mm with 12% lymphoblasts and a platelet count of 93,000/cu mm.

(Received November 1 1, 1974; revision accepted for publi-cation January 22, 1975.)

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794

DURAL

SINUS

OCCLUSION

FIG. 1. Oblique view of right carotid injection demonstrating complete OCclusion of the superior sagittal sinus anteriorly

(

arnw). Para-sinus collaterals are present posterior to the obstruction.

Bone marrow aspiration indicated leukemic relapse. No coagulation studies were performed. An electroencephalo-gram showed generalized slowing. A brain scan was re-ported to be normal; in retrospect, however, a slight in-crease in uptake was noted in the left lateral view involving the area of the superior sagittal sinus, maximally in the pos-tenor two thirds contrasting with decrease in the anterior one third. Increased uptake was noted in the frontal projec-tion in the region of the superior sagittal sinus. A right ca-rotid cerebral artenogram via the femoral route was per-formed following the infusion of four units of platelet concentrate without complications. No evidence of an in-tracranial mass was seen with normal arteriovenous

circula-tion

and no focal arterial abnormalities; however, the lat-eral venous phases of six and seven seconds showed filling of the frontal cortical veins but no filling of the parietal and

occipital

cortical veins. One cortical vein appeared to have an intraluminal filling defect. There was good filling of the torcular, straight, and lateral sinuses as well as the jugular veins. An oblique view (Fig. 1) with the head turned to the right showed complete occlusion of the superior sagittal sinus (arrow).

Following cerebral angiography, the patient subsequently underwent craniospinal irradiation with 50 rads directed specifically to the midline. The total dose was 800 rads. Treatment with dexamethasone was continued and he improved symptomatically and was discharged. One month later, however, he was readmitted because of bleeding and despite supportive treatment he died 16 days after this admission.

NEUROPATHOLOGIC

FINDINGS

The

gross

examination

of the

brain,

which

was

the

only

organ

for

which

post-mortem

examina-tion

was

permitted,

showed

complete

occlusion

of

the

superior

sagittal

sinus

throughout

most

of its

length

by

organizing

thrombus

(Fig.

2,

top).

The

only other change noted was mild-to-moderate dilatation

of the

ventricular

system.

Specifically,

no

areas

of encephalomalacia,

hemorrhage,

signs

of

meningitis,

or

gross

tumor

infiltration

were

seen.

The

histological

examination,

however,

showed

prominent

lymphoblastic

infiltration

of the

walls

(Fig.

2,

bottom)

of

the

superior

sagittal

sinus

adjacent

to

the

thrombus.

The

tumor

cells

extended

into

the

thrombus

as

well

as

the

adja-cent

dural

leaflets

and

were

also

seen

in

the

diaphragma sellae overlying the hypophysis.

Lymphoblasts

were

not

seen

in the

leptomeninges

or

brain

parenchyma

and

were

virtually

absent

among

the

blood

elements

of

the

lumina

of

the

cerebral

vessels.

The

thrombus

within

the

superior

sagittal

sinus

was

invaded

by

numerous

fibroblasts

and

well-defined

capillaries.

Centrally

the

erythrocytes

lacked

distinct

cell

boundaries

and

stained

poorly.

No attempt at recanalization was observed.

Only

occasional

neurons

in

the

hypothalamus

showed

acute

anoxic

changes.

DISCUSSION

Reviews

of the

large

series

documenting

CNS

leukemia7’

fail

to

mention

the

occurrence

of

venous

sinus

thrombosis.

Close

scrutiny

of

mdi-vidual

case

reports

in

retrospect

have

suggested

to

us

the

possibility

of

a

diagnosis

of

sinus

thrombosis

in some

cases.

Borgstedt

et al.9

reported

the

case

of a

6-year-old

boy

not

previously

diagnosed

as having

either

peripheral

or CNS

leukemia

who

presented

with

signs

and

symptoms

of

increased

intracranial

pressure

with

no

CSF

pleocytosis,

but

who

on

ventriculography

did

show

a dilated

ventricular

system.

The

child’s

symptoms

persisted

and

two

months

following

the

initial

evaluation

acute

lymphocytic leukemia was diagnosed.

While

Borgstedt

et al. sought to utilize this case to

document

increased

intracranial

pressure

as

an

initial manifestation of acute leukemia, they did

state

that

pleocytosis

was

not

observed

in

the

CSF.

Angiography

was

not

performed

on

this

patient.

A

similar

case

was

described

by

Cres-koff’#{176}

and

another

more

poorly

documented

case

was

described

by

Garvey

and

Lawrence.”

In each

of

these

cases

there

was

evidence

of

increased

intracranial

pressure

but

no

CSF

pleocytosis.

Additionally,

Hyman

et al.8

in their

series

noted

five

patients

on

15 occasions

who

had

signs

or

symptoms of CNS leukemia but no CSF

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FIG. 2. Top, Cross-section of superior sagittal sinus demonstrating occlusion by organizing thrombus (hematoxylin-eosin, x 12). Bottom, The dura mater (D) is infiltrated with lympho-blasts (L) which spill over into thrombus (1’) organized by fibroblasts (F’)

(hematoxylin-eosin, x90).

sis. In one patient, who died 1 1 days after a

negative

CSF

examination,

autopsy

findings

did

not

confirm

the

clinical

presence

of CNS

involve-ment.

Hyman

et a!.

concluded

that

treatment

with

combined

steroid-radiation

therapy

may

have

resulted

in

the

disappearance

of

subarach-noid

infiltrates.

This combined experience from the literature

prompted

d’Ermo

and

Levi’2

to

conclude

that

examination of

the

CSF

should

be

routine

prac-tice

in

leukemia

since

it may demonstrate the

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simi-796

DURAL

SINUS

OCCLUSION

larly concluded that CNS arachnoidal infiltration may be present in children with acute leukemia

without

apparent

CNS

symptoms

and

without

abnormal

findings

in

the

spinal

fluid

and

that

occasionally a

child

with

arachnoidal

leukemia

will

have

normal

CSF

findings.

He

does

not

cite

venous sinus obstruction as cause for increased

intracranial

pressure

in

these

patients.

Our

experience

coupled

with

a review

of

the

literature

suggests

that

dural

sinus

thrombosis

could

be

a more

frequent

occurrence

in

acute

lymphocytic leukemia than previously

appre-ciated.

The

failure

to recognize

similar

cases

may

be related to two factors: most hematologists, as

well

as other

physicians,

are

reticent

to

perform

angiography in the presence of

thrombocytope-nia,

and

pathologists

may

fail

to

examine

the

superior sagittal sinus at autopsy routinely.

Further,

the

angiographic

diagnosis

may

be

diffi-cult

to establish

and

require

special

techniques.’4

In our case there was no complication to selective

carotid

arteriography,

but

a noninvasive

proce-dure such as serial brain scans, demonstrating

prolonged

uptake

in sinus

thrombosis,

or

isotope

cysternography may offer a clue that this is the

actual

and/or

contributive

basis

for

the

develop-ment

of increased

intracranial

pressure.

Further,

once

this

diagnosis

is

established,

radiation

therapy directed to this area or other treatment

directed

to

the

intravascular

compartment

may

be

much

more

propitious

than

the

traditional

approach

of

intrathecally

given

medication

or

craniospinal

irradiation.

While

our patient developed dural sinus occlu-sion in relapse, we wonder whether the potential

for

development

does

not

exist

even

in remission.

The

cause

of

thrombosis

is conjectural.

It

could

possibly be related to antileukemic agents, the primary disease process (infiltration of the sinus),

or

both.

It

is also

possible

that

this

may

occur

concomitantly with typical CNS leukemia.

While

causes

of

increased

intracranial

pressure

may yet be identified, we feel that dural sinus

occlusion

should

be

kept

in

mind

and

excluded

primary or concomitant process in these

patients.

REFERENCES

1. Russell DS, Rubinstein U: Pathology of Tumors of the Nervous System. Baltimore, Williams & Wilkins Go, 1971, p 75.

2. Freireich EJ, Thomas LB, Frei E et al: A distinctive type of intracerebral hemorrhage associated with “bIas-tic crisis” in patients with leukemia. Cancer 13: 146, 1960.

3. Moore EW, Thomas LB. Shaw RK, Freireich EJ: The central nervous system in acute leukemia. Arch Intern Med 105:451, 1960.

4. Shaw RK, Moore EW, Freireich EJ, Thomas LB: Menin-geal leukemia: A syndrome resulting from increased intracranial pressure in patients with acute leuke-mia. Neurology 10:823, 1960.

5. Leidler F, Russell WO: Brain in leukemia: Clinicopatho-logic study of 20 cases with review of literature. Arch Pathol 40:14, 1945.

6. Critchley M, Greenfield JG: Spinal symptoms in chlo-roma and leukemia. Brain 53: 1 1, 1930.

7. Price HA, Johnson WW: The nervous system in child-hood leukemia: 1. The arachnoid. Cancer 31:520,

1973.

8. Hyman C, Bogle

J,

Brubaker C, et al: Central nervous system involvement by leukemia in children. Blood

25:1, 1965.

9. Borgstedt A, MagilI F, Miller D, et al: Increased intracranial pressure, initial manifestation of acute leukemia. NY State J Med 70:2112, 1970.

10. Creskoff AJ: Leukemia: oddities in onset and course. Med Clin North Am 37:1747, 1953.

11. Garvey PH, Lawrence JS: Facial diplegia in lymphatic

leukemia, JAMA 101:1951, 1933.

12. d’Eramo M, Levi M: Neurological Symptoms in Blood Diseases. Baltimore, University Park Press, 1972, p

111.

13. Pochedly C: The Child with Leukemia. Springfield, Illinois, Charles C Thomas, 1973, 64.

14. Vines FS, Davis DO: Clinical-radiological correlation in cerebral venous occlusive disease. Radiology 98:9,

1971.

ACKNOWLEDGMENT

Mrs. Marlynn Morrill provided invaluable assistance in the preparation of this manuscript.

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1975;56;793

Pediatrics

Ronald B. David, M. Gary Hadfield, Frederick S. Vines and Harold M. Maurer