CASE REPORT

published: 30 August 2021

doi: 10.3389/fneur.2021.675083

Progressive Stroke Caused by

Neurosyphilis With Concentric
Enhancement in the Internal Cerebral
Artery on High-Resolution Magnetic
Resonance Imaging: A Case Report
Kejia Zhang 1,2,3 , Fengna Chu 1,2,3 , Chao Wang 1,2,3 , Mingchao Shi 1,2,3*† and Yi Yang 1,2,3*†
1
Stroke Center & Clinical Trial and Research Center for Stroke, Department of Neurology, The First Hospital of Jilin University,
Edited by: Changchun, China, 2 China National Comprehensive Stroke Center, Changchun, China, 3 Jilin Provincial Key Laboratory of
Linda Chang, Cerebrovascular Disease, Changchun, China
University of Maryland, United States

Reviewed by:
Background: Neurosyphilis can initially present as a stroke. However, the general
Tian-Ci Yang,
Xiamen University, China management strategy for stroke may not be effective for this condition. Intracranial vessel
Xianjin Zhu, wall imaging indicating arteritis can help differentiate neurosyphilis from other causes
Capital Medical University, China
Zhongrong Miao, of stroke.
Capital Medical University, China
Case presentation: A 59-year-old Chinese woman presented with an acute infarct
*Correspondence:
in the left basal ganglia and multiple stenoses in the bilateral middle cerebral arteries,
Mingchao Shi
superstone@jlu.edu.cn anterior cerebral artery, and basilar artery, which aggravated twice, despite antiplatelet
Yi Yang treatment. High-resolution magnetic resonance imaging (HR-MRI) suggested concentric
yang_yi@jlu.edu.cn;
doctoryangyi@163.com
enhancement in the left middle cerebral artery. Treponema pallidum test results were
positive, suggesting neurosyphilis.
† These authors have contributed
equally to this work Conclusions: HR-MRI provides valuable information regarding arteritis, which is helpful
in differentiating neurosyphilis from other causes of stroke. Antiplatelet medication should
Specialty section:
This article was submitted to
be used judiciously for neurosyphilis-related stroke.
Neuroinfectious Diseases, Keywords: stroke, high resolution magnetic resonance imaging, neurosyphilis, meningovascualr syphilis,
a section of the journal neurosyphilic arteritis
Frontiers in Neurology

Received: 02 March 2021

Accepted: 22 July 2021 INTRODUCTION
Published: 30 August 2021

Citation: Syphilis, a sexually transmitted disease, is caused by Treponema pallidum. Neurosyphilis occurs
Zhang K, Chu F, Wang C, Shi M and when T. pallidum invades the central nervous system, which may initially present as a stroke (1, 2).
Yang Y (2021) Progressive Stroke For these patients, the general management strategies for stroke, including the use of antiplatelet
Caused by Neurosyphilis With and anticoagulant agents, may be less effective. Therefore, the identification of neurosyphilis during
Concentric Enhancement in the
the early stages of the disease is essential. Apart from serum or cerebrospinal fluid (CSF) findings
Internal Cerebral Artery on
High-Resolution Magnetic Resonance
of T. pallidum, high-resolution magnetic resonance imaging (HR-MRI) indicating arteritis can
Imaging: A Case Report. help differentiate neurosyphilis from strokes caused by other factors (3, 4). Here, we present a
Front. Neurol. 12:675083. unique case of progressive stroke caused by neurosyphilis and radiological characteristics of the
doi: 10.3389/fneur.2021.675083 intracranial vessel wall imaging.

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Zhang et al. HR-MRI for Neurosyphilis-Induced Stroke

FIGURE 2 | Magnetic resonance angiography. Multiple stenoses in the

bilateral middle cerebral arteries, anterior cerebral artery, and basilar artery. The
red arrows indicate stenosis.

and stenosis in the bilateral middle cerebral arteries (MCA),

anterior cerebral artery (ACA), and basilar artery (BA) were
noted (Figure 2). The standard therapy for stroke management,
including aspirin, clopidogrel, atorvastatin, butylphthalide, and
FIGURE 1 | Magnetic resonance imaging (MRI). The first MRI suggests an
acute infarct in the left basal ganglia. The second MRI scan suggests an edaravone, was administered continuously.
expanded infarct in the left basal ganglia. The third MRI suggests acute Routine serology and hematological tests suggested elevated
infarction in the left basal ganglia and right callosum genu and bleeding in the blood glucose levels with a fasting blood glucose of 6.37 mmol/L,
left basal ganglia. MRI, magnetic resonance imaging; T1WI, T1-weighted 2 h post-prandial blood glucose of 8.62 mmol/L, and glycosylated
imaging; T2WI, T2-weighted imaging; DWI, diffusion-weighted imaging.
hemoglobin level of 6.10%. Blood pressure, serum homocysteine
levels, and electrocardiography and echocardiography results
were normal. Other risk factors for cerebral vascular disease were
CASE PRESENTATION not remarkable.
Serum T. pallidum particle agglutination (TPPA) was positive,
A 59-year-old Chinese woman was hospitalized due to and the rapid plasma reagin assay (RPR) value was 1:16. A lumbar
bradyglossia and weakness of the right lower limb. She denied puncture was performed, and the results showed that the CSF
smoking, drinking, hypertension, diabetes mellitus, coronary was clear with a pressure of 110 mm H2 O. CSF protein (0.67
heart disease, and previous stroke. MRI suggested an acute g/L, 0.15–0.44) and leukocyte (148 × 106 /L, normal 0–8) levels
infarct in the left basal ganglia (Figure 1) and the right posterior were elevated with a positive Pandy test. CSF TPPA test results
horn of the lateral ventricle. Aspirin, clopidogrel, atorvastatin, were positive, while RPR results were negative. No chancres or
and butylphthalide were initiated based on a diagnosis of any other signs of syphilis were identified. The patient denied
ischemic stroke. promiscuity. Her husband died 5 years ago. However, the patient
Unfortunately, her clinical symptoms deteriorated 16 days used to get pedicures.
after disease onset. She could not walk independently and Intracranial vessel wall imaging with HR-MRI and cognitive
leaned to the right side. Drooping of the right angulus oris scales was performed. Concentric contrast enhancement of
was also noted. The patient was then admitted to our stroke the vessel walls was observed in the left MCA and ACA
center. Neurological examinations identified hemiglossoplegia, (Figure 3). The enhancement was observed in the entire M1
prosopoplegia, paraparesis of the right limb (5–/5), bradyglossia, segment of the left MCA and A1 segment of the ACA,
and positive Babinski and Chaddock signs. Muscle tone, deep which was uniform, continuous, and similar in intensity. In
tendon reflexes, cerebellar signs, sensory abnormalities, and the contralateral MCA, ACA, and BA, the enhancement was
cranial nerves were unremarkable. The National Institutes of not remarkable. Syphilitic arteritis was thus considered in
Health Stroke Scale score was assessed as 2. A repeat brain the left ACA and MCA, and the infarct in the left basal
MRI suggested expanded infarct lesions in the left basal ganglia ganglia could be explained accordingly. The Mini-Mental State
(Figure 1). New lacunar infarct lesions in the right corona radiata Examination score was 23/30, and the Montreal Cognitive

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Zhang et al. HR-MRI for Neurosyphilis-Induced Stroke

FIGURE 3 | High-resolution magnetic resonance imaging. Concentric enhancement in the left middle cerebral artery and anterior cerebral artery. Red circles suggest
vessel wall enhancement.

FIGURE 4 | Timeline of stroke aggravation and intervention. Stroke occurred on day 1 and was aggravated twice (days 16 and 30). Hexadecadrol was initiated on day
23, roxithromycin was initiated on day 27, and roxithromycin was replaced with doxycycline on day 30. The patient was discharged on day 41.

Assessment score was 17/30. Cognitive impairment, neurological On the third day following antibiotic initiation, the
impairment, damage to intracranial arteries, positive CSF TPPA neurological function of the patient deteriorated again,
test results, and elevated CSF protein levels and leukocyte which was accompanied by severe diarrhea. Muscle strength
counts were identified. Neurosyphilis, as generalized paresis of the right side declined with upper limbs measuring one-
of the insane and meningovascular syphilis, was considered. fifth and lower limbs measuring three-fifths. Her brain
Antibiotic treatment was initiated. Roxithromycin (500 mg, four MRI suggested acute infarction in the left basal ganglia
times orally per day) was administered as the patient was and right callosum genu and bleeding in the left basal
allergic to penicillin and ceftriaxone. Hexadecadrol was initiated ganglia (Figure 1). Considering that diarrhea may be a
3 days prior to roxithromycin administration, to prevent the side effect of roxithromycin, roxithromycin was replaced
herxheimer reaction. by doxycycline (0.1 g) intravenously twice a day. The

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Zhang et al. HR-MRI for Neurosyphilis-Induced Stroke

timeline of stroke aggravation and intervention is shown in perforating arteries originating from the MCA and ACA. We
Figure 4. propose that the abnormality of the vessels caused by arteritis in
Fourteen days after antibiotic treatment, the clinical the left MCA and ACA destroyed the orifice of the lenticulostriate
symptoms of the patient did not improve remarkably, with a arteries, leading to ischemic lesions in the left basal ganglia.
serum RPR of 1:16. The patient was discharged and visited a Arteritis in the lenticulostriate arteries might have also existed
venereal disease hospital for further treatment. in the present case, although it was difficult to observe on
radiological images. Both large and small arteries can be affected.
DISCUSSION Heubner arteritis and Nissl-Alzheimer arteritis can also occur
concomitantly. Pathological examination may provide valuable
Syphilis, caused by T. pallidum, is a sexually transmitted information regarding the affected arteries. Multiple stenoses,
disease. Syphilis can invade many organs, including the central including the right ACA, MCA, and BA, were observed in this
nervous system. Neurosyphilis, including meningovascular case, while the enhancement of the affected vessel wall was
syphilis, parenchymatous syphilis, syphilitic meningomyelitis, not obvious. Similar stenosis has also been reported in other
tabes dorsalis, general paresis, and gummas, can occur during any studies, and the reasons may be the inactive phases of arteritis
disease stages (1). or concomitant atherosclerosis (11, 12). Considering that the
The invasion of T. pallidum in the central nervous system infarct area of the left basal ganglion could be explained by the
may cause immune cell aggregation and subsequent immune blockage of the left lenticulostriate arteries, whereas no severe
responses. Following invasion by spirochetes, lymphocytes, infarct was identified in the right hemisphere, syphilitic arteritis-
plasma cells, and other immune cells are infiltrated into the induced blood flow arrest may account for the necrosis of certain
meninges and meningeal vessels. Subsequently, the cerebral brain areas. The characteristics of syphilitic arteritis on HR-
arteries and brain parenchyma can be affected, causing MRI are rarely reported in the literature. Therefore, our case
parenchymatous syphilis and meningovascular syphilis. Heubner provides valuable information regarding the radiological features
arteritis, mainly affecting the medium or large arteries, of syphilitic arteritis.
is characterized by intimal fibroblastic proliferation, medial No international diagnostic criteria for neurosyphilis have
thinning, adventitial inflammation, and fibrosis (5). Nissl- been proposed to date. A Chinese clinical guideline indicated that
Alzheimer arteritis mainly involves the small vessels and is CSF protein level ≥0.5 g/L, leukocyte count >10 × 106 /L, and
characterized by adventitial and intimal thickening (5, 6). Arterial positive non-treponemal or treponemal may be indicative of a
stenosis or occlusion caused by syphilitic arteritis may lead to diagnosis of neurosyphilis (13). In the present case, CSF TPPA
ischemic stroke (7). test results were positive, together with elevated CSF protein
Accurate diagnosis of neurosyphilis is difficult due to the wide levels and leukocytes. However, the CSF RPR test results were
range of potential clinical symptoms. It has been reported that negative, while both RPR and TPPA test results were positive in
stroke, as the first symptom, is found in 14.09% of individuals the serum. One potential explanation is that the non-treponemal
with neurosyphilis, while meningovascular syphilis accounted for test has a high specificity but low sensitivity. In contrast, the
most neurosyphilis cases (8). It is also difficult to differentiate treponemal test has a high sensitivity but low specificity (2, 14).
neurosyphilis from an ischemic stroke during the early disease It is not reliable to use a single test to identify neurosyphilis.
period. In this case, the patient first presented with stroke Both non-treponemal and treponemal tests of the serum and CSF
and multiple stenoses in the cerebral arteries. The common should be performed.
risk factors for stroke were absent, except for impaired glucose The neurological symptoms of the patient deteriorated twice.
tolerance. We believe that the elevated blood glucose levels alone In the local hospital, the syphilitic etiology was not identified,
were not sufficient to explain such severe arterial stenosis. HR- and only ordinary stroke therapy was administered. The second
MRI was performed to determine other possible causes. On HR- aggravation occurred during antisyphilis therapy. The patient
MRI, arteritis normally presents with concentric enhancement, was allergic to both penicillin and ceftriaxone; therefore,
which is segmental, uniform, and circular, and encloses the roxithromycin was administered instead. Erythromycin was
border of the artery with homogeneous signal intensity. In orally administered. However, it was less effective and did
contrast, atherosclerotic stenosis tends to present with eccentric not readily infuse the brain (1, 14). Diarrhea is a potential
enhancement with irregular and heterogeneous wall thickening. side effect of erythromycin use, which may cause dehydration
In contrast, reversible vasoconstriction syndrome presents as and hypoperfusion. Roxithromycin was then replaced with
diffuse, uniform, continuous wall thickening and enhancement doxycycline. Another possible reason for the second aggravation
with less signal intensity (9, 10). may be hemorrhagic transformation. Antiplatelet therapy was
In our case, concentric vessel wall enhancement in the administered initially. Most cases of meningovascular syphilis
left MCA was observed. The entire M1 segment of the left present with stroke (8) and many specialists use antiplatelet
MCA and the A1 segment of the left ACA were involved, regimens (3, 7). However, there are no recommendations (7,
suggesting a high possibility of arteritis. Previous studies have 14–17). Intracerebral hemorrhage in neurosyphilis is rarely
reported similar concentric enhancement in the BA due to reported (18, 19). Antiplatelet therapy and reperfusion may
syphilitic arteritis (3, 4). Concentric enhancement on HR-MRI increase the risk of hemorrhagic transformation. Some previous
may help identify syphilitic arteritis. Infarction of the left basal studies have reported that meningovascular syphilis causes
ganglia was observed in our case, which was nourished by not only arterial stenosis but also aneurysmal dilation or
the lenticulostriate arteries. The lenticulostriate arteries were dissection, which may rupture leading to hemorrhage (19). The

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Zhang et al. HR-MRI for Neurosyphilis-Induced Stroke

administration of antiplatelet therapy in neurosyphilis should be DATA AVAILABILITY STATEMENT

judiciously considered.
This case has several implications for the future management The original contributions presented in the study are included
of neurosyphilis presenting with stroke. (1) HR-MRI findings in the article/supplementary material, further inquiries can be
of neurosyphilis have rarely been reported. This case provides directed to the corresponding author/s.
the enhancement patterns of neurosyphilis arteritis on HR-MRI.
(2) Antiplatelet medication should be judiciously administered ETHICS STATEMENT
since there is a potential risk of hemorrhagic transformation. Our
study had some limitations. (1) Pathological examination was not The studies involving human participants were reviewed and
performed because the patient declined examination. (2) Follow- approved by the Human and Research Ethics committees of
up HR-MRI is needed to better understand the dynamic changes the First Hospital of Jilin University. The patients/participants
in the enhancement patterns of neurosyphilis arteritis. provided their written informed consent to participate in
this study.
CONCLUSION
AUTHOR CONTRIBUTIONS
This case report described a patient with neurosyphilis
who initially presented with aggravated stroke. HR-MRI KZ: organization and drafting and review of the manuscript.
showed concentric enhancement in the internal cerebral FC: review and critique of the manuscript. CW: review of the
artery, suggesting arteritis, which is helpful in differentiating manuscript and improvement of English expressions. MS and
neurosyphilis from other cause-induced strokes. Antiplatelet YY: conception, organization, execution of the manuscript, and
medication should be used judiciously for neurosyphilis- review and critique of the manuscript. All authors contributed to
related stroke. the article and approved the submitted version.

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