Download Superior Sagittal Sinus Thrombosis With Infarction in Sickle Cell Trait

656
Superior Sagittal Sinus Thrombosis With
Infarction in Sickle Cell Trait
John A. Feldenzer, Matthew J. Bueche, Joan L. Venes, and Stephen S. Gebarski
An adolescent female with sickle cell trait presented with acute neurologic deterioration during
treatment for pseudotumor cerebri. Cranial computed tomography, initially normal, subsequently
revealed multiple hemorrhagic infarctions. Suspected superior sagittal sinus thrombosis was confirmed by cerebral angiography. Superior sagittal sinus thrombosis associated with sickle cell trait is
exceedingly rare, and the accompanying increased intracranial pressure may require aggressive
management. (Stroke 1987; 18:656-660)
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
C
erebrovascular complications of sickle cell disease are well known, while cases associated
with sickle cell trait are rare. Only 2 cases
of superior sagittal sinus (SSS) thrombosis and sickle
cell trait, confirmed by hemoglobin electrophoresis,
have been reported in the English literature. 12 In both
cases, SSS thrombosis followed a recently administered general anesthetic. To our knowledge, this is the
first case of sickle cell trait complicated by SSS thrombosis in which another precipitating cause could not be
identified.
Report of a Case
A previously healthy, 17-year-old right-handed
black female was admitted to a local hospital with a
diagnosis of pseudotumor cerebri. She had an 8-week
history of intermittent blurred and double vision and
progressive generalized headaches. Lethargy and
vomiting developed the week before admission. Just
prior to admission, cranial computed tomography (CT)
with (Figure 1) and without i.v. contrast material was
normal. Severe papilledema was detected along with a
slight left sixth nerve palsy on the day of admission.
Medical history included asymptomatic sickle cell
trait, an ovarian cyst, and irregular menses. She had
gained approximately 20 pounds in 3 months and was
taking multivitamins. No other medications, including
oral contraceptives, had been used in the past year.
There was no history of recent trauma, fever, infection, coagulopathy, or alcohol or i.v. drug abuse. The
patient did not smoke. Family history revealed sickle
cell trait in the father and pseudotumor cerebri in the
mother during a pregnancy. The physical examination
was normal except for bilateral papilledema with retinal hemorrhage on the right, decreased visual acuity
on the left, and a mild sixth nerve paresis. Serum
electrolytes and complete blood count were normal.
From the Department of Surgery, Section of Neurosurgery
(J.A.F., M.J.B., J.L.V.) and the Department of Radiology, Section of Neuroradiology (S.S.G.), University of Michigan, Ann
Arbor, Michigan.
Address for reprints: John A. Feldenzer, MD, Section of Neurosurgery, Room 2128 Taubman Health Care Center, University of
Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109.
Received August 21, 1986; accepted November 24, 1986.
CT with and without i.v. contrast material was repeated and was normal. A lumbar puncture revealed an
opening pressure of > 5 5 cm. The patient was treated
with 8 mg q. 6 h. dexamethasone, 35 mg b.i.d. furosemide, and 250 mg q. 6 h. acetazolamide. Initial cerebrospinal fluid (CSF) analysis showed glucose, 60
mg% (serum, 87); protein, 13 mg%; 1 white blood
cell/mm3; 7 red blood cells/mm3; no organisms on
Gram stain; and no growth on bacterial cultures. She
underwent daily lumbar punctures (cultures negative)
with a normal opening CSF pressure on the fourth day.
The patient remained alert, but with persistent headache despite low CSF pressure. On the sixth day, she
became increasingly lethargic with worsening headache. Within 24 hours, she was deeply comatose with
a left hemiparesis. CT without i.v. contrast material
(Figure 2) showed peripheral hemorrhagic lesions suggesting dural venous sinus thrombosis. SSS thrombosis was confirmed by cerebral angiography (Figure 3).
The patient was started on i.v. antibiotics and heparin
(1,000 U/hr) and transferred to the University of
Michigan for further treatment.
Our initial examination revealed normal vital signs
in a comatose patient with papilledema, anisocoric
pupils (left > right) reactive to light, a right sixth
cranial nerve palsy, left central seventh cranial nerve
palsy, and a left hemiparesis. She responded to deep
painful stimuli only. Because of hemorrhages on recent CT (Figure 2), heparin was discontinued. Laboratory values revealed hematocrit, 43.7; white cell
count, 26,000 with a left-shifted differential; platelets,
338,000; prothrombin time, 12.2 seconds; thrombin
clotting time, 17.9 seconds (normal, 8.0-10.0 seconds); and fibrinogen, 302 mg% (normal, 150-350
mg%). Hemoglobin electrophoresis confirmed 38.5%
S, 57.9% A, and 3.6% A2. Antithrombin III level and
electrolytes were normal, and a pregnancy test was
negative.
The patient was given anticonvulsant prophylaxis
(100 mg t.i.d. phenytoin), 0.25 gm/kg q. 2 h. mannitol, and was continued on dexamethasone. Transfusion with packed red cells reduced the hemoglobin S
content to 24.1%. A ventriculostomy was placed
after the partial thromboplastin time had returned to
normal. CSF opening pressure was > 50 cm. Ventricu-
Feldenzer et al
Sinus Thrombosis in Sickle Cell Trait
657
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
FIGURE 1. Before hospital admission. Computed tomography (CT) with i.v. contrast material. This normal study was obtained
during outpatient treatment for pseudotumor cerebri (see text). The prominent enhancement in the region of the straight sinus was not
visualized on the noncontrast CT.
lar drainage was set at 20 cm, and she was intubated
and hyperventilated to PCO2 = 25 mm Hg. Hypertension (maximum, 170/108 mm Hg) was vigorously controlled with methyl dopa, sodium nitroprusside, and
hydralazine.
Three days after transfer, severe intracranial pressure (ICP) spikes (>60 cm) occurred despite hyperventilation, osmotic diuresis, ventricular drainage,
sedation with morphine sulfate, and neuromuscular
blockade with pancuronium bromide. Pentobarbital
coma was induced, and a burst-suppression pattern
was demonstrated on EEC ICP spikes (> 60 cm) con-
tinued for several days, and pentobarbital was discontinued after 4 days. CT showed no significant
change in the left hemispheric hemorrhagic venous
infarcts. Continuous ventricular CSF drainage (400470 ml/day) with intermittent mannitol controlled ICP
below 30 cm. Neurologic improvement occurred gradually with spontaneous eye opening and movement of
the right side. The patient tolerated extubation, and on
the eighteenth day of hospitalization a lumbar-peritoneal shunt was placed after removal of the ventriculostomy. High lumbar CSF pressure was noted
intraoperatively.
FIGURE 2. Sixth hospital day. Computed tomography (CT) with no i.v. contrast material. Multiple left cerebral hemispheric
hemorrhagic venous infarctions. These are most marked in the temporal and parietal lobes.
«58
Stroke
Vol 18, No 3, May-June 1987
/
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
FIGURE 3. Sixth hospital day. Cerebral arteriography subtraction films, late venous phase. Top left: Left common carotid injection, lateral view. Posterior descending portions of the superior sagittal sinus (SSS) do not opacify (open arrows).
The more anterior portions of the SSS may not reliably opacify in normal individuals. Top right: Right common carotid injection, lateral view. The posterior descending portions of the SSS do not opacify. A tangle ofperidural collateral veins is
seen (open arrows). Bottom: Left common carotid injection, oblique view (face
turned toward the left). The above described findings are more dramatically demonstrated (open arrows).
The patient showed dramatic, progressive improvement beginning on the second postoperative day and
was following commands on the fourth day. She was
transferred to the Physical Medicine and Rehabilitation Service and was speaking 2 weeks later. There
was a residual left hemiparesis and cognitive deficits
including verbal apraxia and impairment of immediate
recall and recent memory. Cortical blindness resolved
to 20/50 acuity bilaterally with a dense left homonymous hemianopsia and severe bilateral visual field
constriction. These deficits were progressively improving at the time of her discharge, 5 months after
admission.
Discussion
Sickle cell disease (homozygous sickle cell anemia)
is a well-recognized risk factor for the development of
cerebrovascular thrombosis. 34 The prevalence of cerebrovascular complications may be as high as 17%.5
However, like most other hemoglobinopathies, the
heterozygous form, sickle cell trait, is relatively
asymptomatic. Portnoy and Herion reported a stroke
incidence of 1.7% in 227 patients with sickle cell trait
compared with a 1.8% occurrence of stroke in the
black control group with normal hemoglobin.3 Nevertheless, the surgical and obstetric risks of sudden death
related to hypoxia or vascular stasis are greater than
normal in individuals with sickle cell trait.6 Sudden
death related to hypoxemia and acidosis has been described with sickle cell trait at high altitude.7 McCormick, in an autopsy series of 120 patients with sickle
cell trait, demonstrated massive intravascular sickling
or visceral infarcts (including 2 cerebral infarcts) in
33%. 8 Sickle cell trait was thought to be a major factor
in the death of 12.5% of these patients. In another
series of 175 patients with sickle cell trait, 11 had
neurologic symptoms, but no infarcts were demonstrated.6
There are 13 previously reported cases of cerebrovascular complications associated with sickle cell trait,
including 2 cases of SSS thrombosis.1'28"14 A sickling
crisis associated with the recent administration of gen-
Feldenzer et al
659
Sinus Thrombosis in Sickle Cell Trait
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
eral anesthesia and/or a perioperative hypoxic event
was the proposed etiology in both cases of Schenk1 and
Dalai et al. 2 In our case, there was no known precipitating event or other risk factor.
When erythrocytes containing hemoglobin S are exposed to low oxygen tension, tactoids or polymerized
fibers of abnormal hemoglobin are formed, resulting in
gel formation and abnormal sickle-shaped cells. This
structural change is accompanied by a marked increase
in blood viscosity contributing to stasis. Cerebrovascular thrombosis was traditionally thought to involve
small vessel occlusion secondary to stasis in venules,
capillaries, and precapillary arterioles. However,
Stockman et al reported partial or complete occlusion
of large cerebral vessels by angiography in 6 of 7
patients and concluded that neurologic deficits in sickle cell disease cannot be attributed solely to multiple
small vessel occlusions.15 Large vessel occlusion has
been postulated to result from vascular wall ischemia
resulting in proliferation of the intima and media. Occlusion of the vasa vasorum by sickled cells is the
proposed mechanism of ischemia.15 Postmortem pathologic changes in large cerebral arteries of patients
with sickle cell disease have not been demonstrated
consistently. Dural sinus thrombosis is less common
than occlusion of large or small cerebral arteries. The
pathogenesis of sinus thrombosis most likely involves
stasis caused by increased blood viscosity during hypoxic episodes.
Neurologic complications are often devastating and
progressive in sickle cell disease, and recurrent infarctions are not uncommon. 4 Because an effective antisickling agent has not been developed, acute and prophylactic transfusion regimens have been employed to
reduce the number and percent of circulating hemoglobin S-containing erythrocytes. 1617 The maximum hemoglobin S concentration tolerated in patients without
risk of cerebrovascular thrombosis is unknown. Several studies have demonstrated that cessation of shortterm transfusion was associated with recurrent infarctions, even in cases with < 2 0 % hemoglobin S.
Transfusions of sufficient volume and frequency to
suppress endogenous erythropoiesis are recommended.18"20 Our patient presented with 38.5% hemoglobin
S and received 2 transfusions of packed erythrocytes
during the acute illness. To our knowledge, this is the
first reported case of sickle cell trait with stroke to
undergo transfusion therapy.
In sickle cell trait the hemoglobin S concentration
may vary from 25 to 45%. 21 In vitro studies suggest
that the risk of sickling in sickle cell trait with high
hemoglobin S approaches that in sickle cell disease.22
In our case and the only 3 reported cases of sickle cell
trait with stroke and hemoglobin quantification, hemoglobin S values were > 3 6 % .
SSS thrombosis has been associated with multiple
clinical entities including oral contraceptives, pregnancy, puerperium, dehydration, congestive heart failure, hemolytic anemia, sickle cell disease, cerebral
arterial occlusions, trauma, neoplasm, and others.23"26
The definitive diagnosis is made by cerebral angiog-
raphy. The clinical presentation and ICP dynamics of
SSS thrombosis and pseudotumor cerebri are so similar that some workers consider dural venous sinus
thrombosis as the significant pathogenetic mechanism
for pseudotumor cerebri. Ray and Dunbar demonstrated SSS thrombosis as the cause of pseudotumor cerebri
using sinus venography and surgical exploration in 1
case.27 Bresnan et al were able to show venous sinus
occlusion by angiography in 10 of 12 children with
pseudotumor cerebri.28 It is possible that the occurrence of pseudotumor cerebri in this patient with sickle
cell trait was fortuitous. However, the patient was initially diagnosed with pseudotumor cerebri while, in
fact, she was developing progressive SSS thrombosis.
We feel that the patient's hemoglobinopathy contributed to the SSS thrombosis.
In this case of SSS thrombosis, the associated increased ICP required aggressive treatment. Elevated
ICP may be exacerbated by the mass effect of accompanying hemorrhagic venous infarcts or by surrounding edema. We employed hyperventilation, osmotic
diuresis, steroids, ventricular drainage, sedation, and
barbiturate coma to limit persistently elevated ICP.
Anticoagulant therapy has been utilized since 1942
for the treatment of dural sinus thrombosis.29 It is recommended by some investigators to prevent further
thrombosis,2425 while others consider it contraindicated because of the added risk of intracranial hemorrhage. 233031 We considered the use of heparin contraindicated in our patient with multiple hemorrhagic
infarctions. Tissue plasminogen activator, recently
employed in the treatment of acute coronary thrombosis, may find application in the therapy of dural sinus
thrombosis.
In conclusion: Hemoglobin electrophoresis should
be carried out in young black patients with unexplained
neurologic symptoms or signs. Sickle cell trait in addition to sickle cell disease represents an increased risk
of cerebrovascular thrombosis especially with an elevated level of hemoglobin S (^36%). Dural venous
sinus thrombosis should be considered in patients with
sickle cell disease or trait who are being treated for
pseudotumor cerebri. Increased ICP associated with
dural sinus thrombosis may require aggressive management.
Acknowledgment
We thank Ms. Pat Frye for manuscript preparation.
References
1. Schenk EA: Sickle cell trait and superior longitudinal sinus
thrombosis. Ann Intern Med 1964;60:465-470
2. Dalai FY, Schmidt GB, Bennett EJ, Ramamurthy S: Sickle cell
trait A report of a postoperative complication. Br J Anaeslh
1974;46:387-388
3. Wood D: Cerebrovascular complications of sickle cell anemia.
Stroke 1978;9:73-75
4. Powars D, Wilson B, Imbus C, Pegelow C, Allen J: The
natural history of stroke in sickle cell disease. Am J Med
1978 ;65:461-471
5. Portnoy BA, Herion JC: Neurological manifestations in sickle
cell disease. Ann Intern Med 1972;76:643-652
660
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
6. Greer M, Schotland D: Abnormal hemoglobin as a cause of
neurologic disease. Neurology (NY) 1962;12:114-123
7. Jones SR, Binder RA, Donowho EM Jr: Sudden death in sickle
cell trait. N Engl J Med 1970;282:323-325
8. McCormick WF: Abnormal hemoglobins II. The pathology of
sickle cell trait. Am J Med Sci 1961;241:329-335
9. Thompson RK, Wagner JA, MacLeod CM: Sickle cell disease:
Report of a case with cerebral manifestations in the absence of
anemia. Ann Intern Med 1948;29:921-928
10. Diggs LW, Jones RS: Clinicopathologic conference. AmJClin
Pathol 1952;22:1194-1200
11. Ende N, Pizzolato P, Ziskind J: Sickelemia. Ann Intern Med
1955;42:1065-1075
12. McCormick WF, Schochet SS: Cerebral infarction in sickle
cell disease, in McCormick WF, Schochet SS (eds): Atlas of
Cerebrovascular Disease. Philadelphia, WB Saunders Co,
1976, pp 226-230
13. Handler CE, Perkin GD: Sickle cell trait and multiple cerebral
infarctions. J R Soc Med 1982;75:550-553
14. Greenberg J, Massey EW: Cerebral infarction in sickle cell
trait. Ann Neurol 1985;18:354-355
15. Stockman JA, Nigro MA, Mishkin MM, Oski FA: Occlusion
of large cerebral vessels in sickle cell anemia. A' Engl J Med
1972;287:846-849
16. Lusher JM, Haghighat H, Khalifa AS: A prophylactic transfusion program for children with sickle cell anemia complicated
by CNS infarction. Am J Hematol 1976; 1:265-273
17. Russell MO, Goldberg HI, Reis L, Friedman S, Slater R,
Reivich M, Schwartz E: Transfusion therapy for cerebrovascular abnormalities in sickle cell disease. J Pediatr 1976;88:382387
18. Wilimas J, Goff JR, Anderson HR Jr, Langston JW, Thompson E: Efficacy of transfusion therapy for one to two years in
patients with sickle cell disease and cerebrovascular accidents.
J Pediatr 1980;96:205-208
19. Buchanan GR, Bowman WP, Smith SJ: Recurrent cerebral
Stroke
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Vol 18, No 3, May-June 1987
ischemia during hypertransfusion therapy in sickle cell anemia.
J Pediatr 1983;103:921-923
Seeler RA, Royal JE: Commentary: Sickle cell anemia, stroke
and transfusion. J Pediatr 1980;96:243-244
Neel JV, Wells IC, Itano HA: Familial differences in the proportion of abnormal hemoglobin present in sickle cell trait. J
Clin Invest 1951 ;30:1120-1124
Howells TH, Huntsman RG: Anaesthesia in sickle cell states
(correspondence). Anaesthesia 1973;28:339-341
Gettelfinger DM, Kokmen E: Superior sagittal sinus thrombosis. Arch Neurol 1977;34:2-6
Krayenbuhl HA: Cerebral venous and sinus thrombosis. Clin
Neurosurg 1966;14:l-24
Kalbag RM, Woolf AL: Primary thrombosis of the dural sinuses and anemia, in Kalbag RM, Woolf AL (eds): Cerebral
Venous Thrombosis. London, Oxford University Press, 1967,
pp 90-93
Kalbag RM: Cerebral venous thrombosis, in Kapp JP, Schmidek HH (eds): The Cerebral Venous System and Its Disorders.
Orlando, Fla, Grune & Stratton, 1984, pp 505-536
Ray BS, Dunbar HS: Thrombosis of the superior sagittal sinus
as a cause of pseudotumor cerebri: Methods of diagnosis and
treatment. Trans Am Neurol Assoc 1950;75:12-17
Bresnan MJ, Strand R, Rosenbaum A: Jugular venous block
associated with benign intracranial hypertension (abstract).
Neurology (Minneap) 1973;23:390
Stansfield FR: Puerperal cerebral venous thrombosis treated
with heparin. Br Med J 1942; 1:436-438
Barnett HJM, Hyland HH: Noninfective intracranial venous
thrombosis. Brain 1953;76:36-49
Buchanan DS, Brazinsky JH: Dural sinus and cerebral vein
thrombosis: Incidence in young women receiving oral contraceptives. Arch Neurol 1970;22:440-444
KEY WORDS • dural sinus thrombosis • infarction
cell trait
• sickle
Superior sagittal sinus thrombosis with infarction in sickle cell trait.
J A Feldenzer, M J Bueche, J L Venes and S S Gebarski
Stroke. 1987;18:656-660
doi: 10.1161/01.STR.18.3.656
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1987 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/18/3/656
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click Request
Permissions in the middle column of the Web page under Services. Further information about this process is
available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/