Edwards et al.

Journal of Medical Case Reports 2013, 7:210

http://www.jmedicalcasereports.com/content/7/1/210 JOURNAL OF MEDICAL
CASE REPORTS

CASE REPORT Open Access

A 19-year-old man with sickle cell disease

presenting with spinal infarction: a case report
April Edwards1, E Leila Jerome Clay2,3*, Valerie Jewells4, Stacie Adams5, Regina D Crawford6
and Rupa Redding-Lallinger2

Abstract
Introduction: Vasculopathy of the large vessels commonly occurs in sickle cell disease, and as a result cerebral
infarction is a well characterized complication of this condition. However, spinal infarction appears to be rare. Spinal
infarct is infrequent in the non-sickle cell population as well, and accounts for only about 1 percent of all central
nervous system infarcts.
Case presentation: In the present work, we report the case of a 19-year-old African-American man with sickle cell
disease who experienced an anterior spinal infarct and subsequent quadriplegia. He was incidentally noted to be a
heterozygote for factor V Leiden. We also reviewed the literature and found two previous cases of spinal cord
infarction and sickle hemoglobin. Our literature search did not demonstrate that heterozygocity for factor V Leiden
plays an important role in spinal cord infarction.
Conclusions: The paucity of cases associated with sickle hemoglobin does not allow us to postulate any particular
risk factors with sickle cell disease that might predispose patients to spinal cord infarction. Our patient’s case raises
the question as to whether spinal cord infarction is being missed in individuals with sickle cell disease and
neurologic symptoms.

Introduction has been a description of cord compression by extra-

Cerebral infarction is the most common neurologic medullary hemopoietic tissue in addition to rare case
complication that occurs with sickle cell disease (SCD); reports of spinal cord infarction [1,4-6].
it can be either overt or silent and it can be associated In the non-sickle cell disease population it appears
with significant morbidity [1]. Overt stroke in SCD was that spinal infarct is much less frequent than cerebral
first characterized in 1923, and histopathologic studies infarction as well, and accounts for only about 1 percent
later revealed large vessel narrowing with superimposed of all CNS infarcts [7]. Of those with spinal infarction,
thrombosis as the underlying cause [2,3]. Though cerebral most appear to be from traumatic or surgical etiologies
infarction is the most frequent neurological complication, than other organic causes [7,8]. Aortic disease is a frequent
a number of other potentially devastating central nervous culprit with many case reports detailing adverse sequelae
system (CNS) sequelae have also been described. These following surgical repair of aneurysms, but also aortic
include: intra-cranial hemorrhage, isolated neuropathies, thrombosis, and aortic dissection [8]. Other non-traumatic,
transverse myelitis, auditory and ocular manifestations, non-surgical etiologies of spinal cord infarct include: global
and spinal cord involvement [1]. In the spinal cord there hypotension and/or arterial insufficiency, often after
cardiac arrest; transient ischemic attacks; fibrocartilagenous
emboli; arterial vascular malformations; syphilitic arteritis
* Correspondence: leila.clay@gru.edu
2
Departments of Pediatrics and Internal Medicine, Division of Hematology and adjacent spinal disease [8-10]. In a 2006 study,
and Oncology, University of North Carolina School of Medicine, 170 Novy et al. noted that 12 of their 27 patients with spinal
Manning Drive 1185A, Physician Office Building CB#7236, Chapel Hill, NC infarct had pre-existing spinal disease including com-
27599-7236, USA
3
Departments of Pediatrics and Internal Medicine, Division of Hematology pression fractures, spondylolisthesis, chronic aracho-
and Oncology, Georgia Regents University, 1120 15th Street, BH 2015, noiditis and chronic cervical disk protrusion, and of those
Augusta, GA 30912, USA 12 patients, 11 had an infarct at the level of their pre-
Full list of author information is available at the end of the article

© 2013 Edwards et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Edwards et al. Journal of Medical Case Reports 2013, 7:210 Page 2 of 6
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existing disease [7]. However, the cause of spinal infarct approximately 5:45 p.m. when he used the bathroom,
is frequently cryptogenic [11]. he noticed that he could not pull up his trousers due to
There is considerable evidence that sickle cell disease weakness in his left arm. As he walked out of the bath-
represents a hypercoagulable state [12-15]. It appears room, he noted that he was having difficulty walking
that nearly every component of hemostasis is altered because of weakness in his right leg. As his mother was
to some degree in SCD [15]. Studies have indicated helping him to his bed, his left leg also became weak.
that in sickle cell disease there is increased platelet He began experiencing ‘shocking’ pains on both sides
activation and aggregation, increased levels of D-dimer of his neck, which were unlike his usual pain, and also
and fibrinogen and fibrin-fibrinogen complex while noted that he had an erection. These events transpired
there are simultaneously decreased factors V, VII, VIIa rapidly, within about six minutes, at which point his
and proteins C and S [13]. There is good evidence that family called Emergency Medical Services (EMS) and
there is externalization of phosphatidylserine (a phospho- our patient was transported to our hospital.
lipid normally found in the inner monolayer of red blood On arrival at our hospital, he was alert and oriented
cells) in SCD, which is thought to play a significant role and cranial nerves II to XII were intact. He had flaccid
in promoting macrophage recognition in erythropha- paralysis of the bilateral upper extremities and the left
gocytosis and thus triggering a signal for the coagulation lower extremity, and normal tone with 5 out of 5
process [13,14]. Increased phosphatidylserine exposure strength in the right lower extremity. He had areflexia in
is also thought to be associated with increased tissue the biceps, triceps, and brachioradialis bilaterally, hyper-
factor expression [14]. However, it remains unclear how or reflexia at the left patella, and sustained clonus at the left
to what extent those abnormalities contribute to disease Achilles. Sensation was intact throughout. The results of
complications such as cerebral and spinal infarcts. the rest of his physical examination were normal.
Because cerebral infarcts occur only in a subset of the Relevant medical history included asthma, recurrent
sickle cell population, it has been postulated that there acute chest syndrome (>10 episodes), and intermittent
may be identifiable features of this subgroup that exacer- attempts at hydroxyurea treatment with poor compliance
bate the hypercoagulable state of sickle cell disease. In over the previous 10 years. Following the identification
the search for possible characteristics of this subpopula- of silent cerebral infarcts, he was treated for the three
tion, some have begun to explore factors that predispose years between 2005 and 2008 with exchange transfusions
the general population to coagulation abnormalities and to maintain hemoglobin S < 30 percent; during this time
thrombophilia. Specifically, there have been case reports he did very well. At 10 days prior to presentation, he
of persons with SCD who developed CNS infarcts and was hospitalized with an acute chest syndrome. During
were found to have the factor V Leiden, a prothrombin that hospitalization he had an initial PO2 of 76, a
gene variant, a methylenetetrahidrofolate reductase gene hemoglobin (Hb)/hematocrit (Hct) nadir of 5.8/17, and
mutation, or some combination of those mutations [16-18]. was found to have a methicillin-resistant Staphylococcus
These studies were conducted in Brazil and Israel; not- aureus (MRSA) pneumonia. He was treated with antibi-
ably the prevalence of the factor V Leiden and the pro- otics and a transfusion. His discharge hemoglobin was
thrombin gene variant are known to be very low in 6.6 and oxygen saturation 96 percent. He was without
African-Americans [19]. Also, there have been a few symptoms at the time of discharge.
single nucleotide polymorphisms (SNPs) in persons Admission laboratory test data included a white blood
with SCD that have been found to be associated with cell count of 12 × 103/uL Hb 8.7g/dL, Hct 26 percent,
increased stroke risk: ANXA2, TGFBR3, and TEK were platelets 449 × 103 cells/mm3 with a hemoglobin elec-
noted in a study including these SNPs [20]. However, trophoresis of HbA 86 percent, HbS 7 percent, and HbC
further validation is needed before these can be used to 7 percent. He had a lumbar puncture that demonstrated
prospectively guide recommendations for molecular gen- unremarkable cerebrospinal fluid findings and no evi-
etic testing or treatment [20]. There is no known identi- dence of IgG oligoclonal bands. The results of peripheral
fiable thrombophilic abnormality that predicts cerebral blood and urine cultures were negative. A chest X-ray
infarction in sickle cell disease. showed patchy consolidation in the right upper lobe
suspicious for pneumonia. The results of computed
Case presentation tomography (CT) angiography of the head and neck
On the morning of admission, our patient, a 19-year-old were unremarkable. Given concern for spinal cord in-
African-American man with sickle cell anemia, felt volvement, 1.5T T1, T2, and fluid attenuated inversion
himself to be in his usual state of health, although he recovery (FLAIR) magnetic resonance imaging (MRI)
had just been discharged the previous day from a studies of the brain and cervical spine was performed
hospitalization for acute chest syndrome. He ate break- showing an abnormal T2/FLAIR signal in the cervical
fast and spent the day watching television. However, at spinal cord, which was thought at that time likely to be
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due to artifact. Later the initial MRI was read to also a heparin drip during his stay in the acute care facility, but
show swelling of the cord in the same area. He was this was discontinued on discharge. A monthly exchange
admitted to the neurologic intensive care unit where he transfusion regimen was instituted with the goal of keep-
received an exchange transfusion with no significant ing his hemoglobin S level < 30 percent.
improvement in his symptoms; subsequent hemoglobin Although initially there was almost complete paralysis
electrophoresis showed HbA 85 percent, HbS 9 percent. of his extremities, over the four days he spent in the
While in the intensive care unit (ICU) he experienced neurologic ICU, our patient demonstrated slow but
episodes of hypotension that were initially managed with steady progress in regaining some motor function of his
vasopressors. After his blood pressure stabilized he was affected limbs. He was transferred from the ICU to the
transitioned to fludrocortisone and midodrine. He never wards on day five and began working with physical and
had respiratory insufficiency. Two days after admission occupational therapy. On day 10, he was transferred to a
he had a repeat MRI, which showed T2 hyperintense rehabilitation facility, where he made gradual but steady
signal extending from C2 through to C7 (Figure 1A). In progress in regaining motor function. He was discharged
addition, diffusion-weighted imaging demonstrated re- home after three weeks.
stricted diffusion consistent with a focus of infarction Five months after the acute onset of paralysis, he had
in addition to cord edema and swelling in the gray and some residual left arm and leg weakness and spasticity,
white matter of the right side of the cord. There was but was able to walk unassisted and perform most ac-
associated enlargement of the spinal cord consistent tivities of daily living without assistance. A repeat MRI
with edema from the anterior spinal infarct. A hyperco- scan showed a persistence of slight T2 signal abnormal-
agulability investigation performed during his hospital- ity in the cervical cord, consistent with previous spinal
ization included a polymerase chain reaction (PCR) cord infarction. There was no spinal cord atrophy (Figure 2).
study that demonstrated that he was heterozygous for Our patient continued to make progress, regaining much
the factor V Leiden 1691 G>A mutation. Other studies of his strength and function, and was maintained on a
performed were for factor VIII, fibrinogen, functional regimen of monthly scheduled exchange transfusions.
anti-thrombin, lupus anti-coagulant, anti-cardiolipin, At 18 months post-infarct he presented with complaints
all of which were within normal limits. His erythrocyte of three hours of generalized weakness, worse in his lower
sedimentation rate (ESR) and C-reactive protein (CRP) extremities in association with a pain crisis. His symptoms
levels were both elevated, and proteins C and S were of weakness had largely resolved by the time he arrived
found to be low but within the expected range for some- at our Emergency Department. On examination he had
one with sickle cell disease. He was anti-coagulated with 4 out of 5 strength in his left lower extremity and 5 out

Figure 1 A,B T2 hyperintense signal extending from C2 to C7 with edema of the gray and white matter of the cord. The arrows point to
the edema. As with all infarcts, the area of infarct is bright on B1000 and dark on apparent diffusion coefficient sequences.
Edwards et al. Journal of Medical Case Reports 2013, 7:210 Page 4 of 6
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Figure 2 A,B Follow-up magnetic resonance imaging study demonstrating no spinal cord atrophy with residual signal from
myelomalacia, months after infarct. Arrows point to the decrease in edema.

of 5 in right lower extremity, and 3 out of 5 grip her spinal cord, there were however, many arteries
strength bilaterally with a slightly unsteady gait; these and veins distended with abnormally shaped sickle red
findings were not substantially different from his post- cells [4]. A 1980 case report describes a 19-year-old
spinal cord infarction baseline. His hemoglobin S was African-American man with sickle cell disease who devel-
51.5 percent at that time. Repeat imaging studies of his oped sudden-onset quadriplegia and in post-mortem stud-
brain and spine at that time were unchanged from his ies was found to have multiple, old, focal and confluent
prior studies. He was admitted and had an exchange infarcts involving the cortex and subcortical white matter
transfusion achieving a post-transfusion HbS of 8.3 in the brain, and also of the cervical, thoracic, and upper
percent. He was given daily low-dose (81mg) aspirin. lumbar spinal cord [5]. There are no data from these
Currently, at 20 months post-spinal cord infarction, his case reports in the literature concerning other potential
condition is unchanged. risk factors including any thrombophilic abnormalities, as
these were not commonly looked for in 1970 and 1980.
Discussion From the available reports that have looked for an
Spinal cord infarct is infrequent compared to cerebral in- association between factor V Leiden and complications
farction in the general population, and most commonly of sickle cell disease, there is no evidence of an obvious
occurs as a result of a dissecting aortic aneurysm or aortic relationship [16,21,22]. Kahn et al. studied a cohort of
surgery [7,8]. In persons with sickle hemoglobin, sig- 82 patients with different sickle cell states, 19 of whom
nificant spinal cord infarction appears to be an even had had a stroke [21]. Only one of the 82 was heterozy-
more rare neurologic complication. To the best of our gous for factor V Leiden (there were no homozygotes),
knowledge, there are only two reported cases of other and this was not a patient who had experienced a
persons, both now deceased, detailing this pathology stroke, priapism or any other vascular-type disorder
[4,5]. Of note, the radiographic findings from our patient [21]. Andrade et al. similarly examined a cohort of 73
have been previously presented in a radiology journal patients with sickle cell disease in Brazil, of whom five
with emphasis on the diffusion-weighted images, but in had a stroke [16]. One of the five was a heterozygote for
this report we describe the clinical details and our patient’s factor V Leiden; of the patients who had not experienced
subsequent course [6]. a stroke, none were positive for the factor V Leiden muta-
There is a case report from 1970 of a 59-year-old Jamaican tion. Interestingly, that patient had a sister who also
woman with presumed sickle cell trait who deteriorated had sickle cell anemia and stroke, but the sister did not
over the course of several years to near complete paraplegia carry the factor V Leiden mutation. We conclude that our
and who was subsequently found to have a slightly swollen patient’s heterozygosity for factor V Leiden did not con-
spinal cord in the cervical region and atrophic thoracic tribute to the occurrence of the spinal cord infarction.
and lumbar spine cord segments on autopsy [4]. The au- Our patient has severe sickle cell disease as manifested
thors noted that her vasculature and neural tissue was by multiple bouts of recurrent acute chest syndrome and
otherwise without the stigmata of significant atherosclerotic the presence of a silent cerebral infarction. As a comorbid-
or degenerative disease, and while no thrombosed ves- ity which predisposes to more severe disease, he also has
sels were found in relation to the areas of necrosis in asthma. However, he would not be considered to be very
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unusual in having this degree of illness. Therefore, the Author details

1
question arises as to why he developed the rare compli- Departments of Internal Medicine and Pediatrics, University of North
Carolina School of Medicine, 101 Manning Drive, Chapel Hill, NC 27514, USA.
cation of spinal cord infarction. It occurred during the 2
Departments of Pediatrics and Internal Medicine, Division of Hematology
recovery from an episode of acute chest syndrome, and Oncology, University of North Carolina School of Medicine, 170
which is known to be a time period of increased risk for Manning Drive 1185A, Physician Office Building CB#7236, Chapel Hill, NC
27599-7236, USA. 3Departments of Pediatrics and Internal Medicine,
cerebral infarction, but this is clearly not a full explanation Division of Hematology and Oncology, Georgia Regents University, 1120
given the frequency of acute chest syndrome and the rarity 15th Street, BH 2015, Augusta, GA 30912, USA. 4Department of Radiology,
of spinal cord infarction. His hypoxemia had resolved University of North Carolina School of Medicine, 100 Manning Drive,
Radiology CB#7510, Old Clinic Building, Chapel Hill, NC 27599-7510, USA.
when the spinal cord infarction occurred, and his wors- 5
Department of Pediatrics, Michigan State University, GRMEP 1000 Monroe
ened anemia had been corrected. In addition, his sickle Avenue, NW, Grand Rapids, MI 49503, USA. 6Department of Medicine,
hemoglobin percentage was quite low. Although our Division of Hematology, Duke University Medical Center, 2212 Elba Street
DUMC Box 3939, Durham, NC 27705, USA.
review of the literature does not suggest that his infarct
can be explained by the factor V Leiden heterozygosity, Received: 30 January 2013 Accepted: 27 July 2013
he was not tested for any of the other genetic variants Published: 23 August 2013

that have been recently found to be associated with

stroke in SCD such as ANXA2, TGFBR3, and TEK. It is References
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doi:10.1186/1752-1947-7-210
Cite this article as: Edwards et al.: A 19-year-old man with sickle cell
disease presenting with spinal infarction: a case report. Journal of
Medical Case Reports 2013 7:210.

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