Cerebral infarction as initial manifestation of meningovascular neurosyphilis in an immunocompetent patient – A case report with long term follow‐up

Abstract

To present a 29‐year‐old immunocompetent patient with neurosyphilitic changes characterized by multiple acute ischemic brain strokes along with significant narrowing of several large intracranial arteries. Ceftriaxone treatment for 14 days followed by benzathine benzylpenicillin weekly for additional 3 weeks, showed improvement in meningovascular changes.

Antimicrobial therapy in a 29‐year‐old immunocompetent patient with meningovascular neurosyphilis and subsequent ischemic brain strokes resulted in substantial regression of intracranial vessel changes and complete regression of neurological deficit.

1. INTRODUCTION

Stroke in younger patients is unusual and requires detailed diagnostic work‐up due to possible rare causes such as syphilis infection. ¹ Neurosyphilis is a central nervous system infection caused by Treponema pallidum (TP) that could be a treatable cause of stroke in some circumstances. ² We present a young immunocompetent patient with meningovascular neurosyphilis, vasculitis of large intracranial arteries, and subsequent ischemic brain strokes.

2. CASE REPORT

A 29‐year‐old white man was hospitalized at the Department of Neurology due to sudden motor dysphasia and right arm weakness. The onset of symptoms was preceded by a headache that occurred the day before hospital admission. The patient had a mild form of coronavirus disease 2019 6 months prior to admission, and a year earlier was assessed by a dermatologist due to a non‐specific generalized rash without the need for specific medication.

Upon admission, emergency computed tomography of the brain was unremarkable. Further diagnostic imaging assessment was supplemented with magnetic resonance imaging (MRI) and MRI angiography (MRA). Several acute ischemic changes in the left middle cerebral artery territory involving the basal ganglia as well as cortical and subcortical areas were detected on the brain MRI (Figure 1A,B). MRA of the brain showed significant narrowing of the middle third of the basilar artery, the terminal segment of the left internal carotid artery and of the left A1 and M1 segments (Figure 2A–D). These stenoses were indicative of a possible underlying vasculitis.

FIGURE 1.

Magnetic resonance of the brain at onset. (A) Diffusion‐weighted imaging, and the corresponding (B) apparent diffusion coefficient map showing acute ischemic infarcts (red arrows) involving the left caudate nucleus, left corona radiata as well as a small cortical and subcortical area of the left parietal lobe.

FIGURE 2.

Three‐dimensional time‐of‐flight magnetic resonance angiography (MRA) of the brain at onset and 1 year after onset. (A) Coronal reconstruction of the MRA at onset showing significant narrowing of the terminal left internal carotid artery (ICA) segment (white arrow), left A1 segment (yellow arrow) and left M1 segment (red arrow). (B) MRA axial image at onset through the terminal left ICA segment presenting significant narrowing (dotted circle). (C) Maximum intensity projection MRA and (D) an MRA axial image displaying a high‐grade stenosis of the middle part of the basilar artery (white arrow and dotted circle, respectively). (E) Coronal reconstruction of the MRA done 1 year after onset showing almost complete regression of the terminal ICA segment narrowing (white arrow), complete regression of the left A1 segment narrowing (yellow arrow) and persistent narrowing of the left M1 segment. (F) MRA axial image 1 year after onset through the terminal left ICA segment presenting almost complete regression of the narrowing (dotted circle). (G) Maximum intensity projection MRA and (H) an MRA axial image displaying almost complete regression of the high‐grade stenosis of the middle part of the basilar artery (white arrow and dotted circle, respectively).

Due to the above, a more detailed laboratory analysis followed. Serological testing for TP was performed, resulting in a positive anti‐TP test (titer 1:81,920) in sera. Human immunodeficiency virus and hepatitis markers tests were negative. Cerebrospinal fluid (CSF) findings showed lymphocytic pleocytosis (651/3 × 10⁶/L) with mild elevation of protein level (0.6 g/L), while CSF‐specific anti‐TP IgG antibodies were also detected. Therefore, antimicrobial therapy of ceftriaxone 2 g intravenously (i.v.) twice a day for 14 days was administered, followed by benzathine benzylpenicillin intramuscularly (i.m.) in the dose of 2.4 million International Units once a week for additional 3 weeks. Antiplatelet therapy with aspirin in oral dose of 100 mg daily was introduced from symptoms onset and remains uninterrupted until now. In addition, echocardiography, carotid artery Doppler ultrasound examination, electroencephalography, as well as immunological and coagulation findings were normal. Serological tests for Brucella, tuberculosis, and Toxoplasma gondii were negative, whereas cytomegalovirus, herpes simplex virus, and Epstein–Barr virus were only IgG positive.

CSF analysis done after 2 weeks of antimicrobial treatment demonstrated milder pleocytosis (183/3 × 10⁶/L). On the first follow‐up radiological examination done with a head CT angiography, 3 months after antimicrobial treatment, the intracranial arteries were of unchanged appearance. The patient's neurological examination 10 months after antimicrobial treatment was unremarkable. Serum and CSF analysis done at the same time showed a significant decrease of TP antibodies in titer of 1:2560 and 1:80, respectively, while other serum and CSF findings were normal. On the brain MRI and MRA performed 1 year after the onset of symptoms, most intracranial arteries displayed substantial regression of the stenoses, without new affected segments, and progression of existing stenoses (Figure 2E–H).

3. DISCUSSION

Syphilis is a sexually transmitted disease that can cause neurological complications. Neurosyphilis has an early and late form. In the early form of neurosyphilis, the meninges and brain blood vessels are dominantly affected, causing meningitis, vasculitis, or meningovascular syphilis. In the later form of neurosyphilis, the disease spreads to the brain parenchyma and spinal cord. ³

In this case, we presented a young immunocompetent patient with meningovascular syphilis who had the clinical picture of an acute stroke. ⁴ Stroke is the initial manifestation in 3% of all syphilis patients and 10% of neurosyphilis patients. ⁵ Neuroradiological examination revealed multiple ischemic brain infarcts with intracranial blood vessel changes due to vasculitis. The mentioned changes predominantly affected large intracranial arteries. The involvement of large intracranial arteries in different blood supply areas is one of the essential characteristics of neurosyphilis. ⁶ , ⁷ , ⁸ Multiple infarctions without other risk factors required a more detailed diagnostic assessment of this patient. Meningovascular syphilis most frequently occurs in the early stage of the disease, more often in homosexual men aged 20–35. ¹ Our patient was not homosexual and not HIV positive, which is also one of the risk factors for syphilis. ⁹ Vasculitis in patients with neurosyphilis occurs in two main forms: Heubner's arteritis, which affects medium and large blood vessels, and Nissl‐Alzheimer's arteritis, which affects the small blood vessels of the brain. ¹⁰ , ¹¹ The mentioned forms are based on a chronic infection that leads to inflammation and fibrous changes in the vascular adventitia, leading to mural thrombi formation and ultimately blood vessel occlusion with consequent stroke. The most common localization is the middle cerebral artery and afterward the basilar artery, as in the case of this patient.

Although parenteral penicillin G is generally recommended by treatment guidelines, ¹² our patient was treated with ceftriaxone i.v. as an alternative therapy due to availability problems of some penicillin medications in Bosnia and Herzegovina. Afterward, the treatment was continued with benzathine penicillin G i.m. weekly for additional 3 weeks. Such treatment resulted in an almost complete regression of stenoses that involved major intracranial arteries on a late follow‐up MRA done months after antimicrobial treatment. This is also in a line with previously described results, confirming the treatment effectiveness which could be used as a non‐invasive biomarker of treatment response. ¹³ Furthermore, in our patient corticosteroids were not applied, although some authors recommend them for meningovascular neurosyphilis treatment. ¹³ , ¹⁴ According to the treatment of our patient whom corticosteroids were not given, an antimicrobial treatment given only might guarantee a favorable therapeutic effect.

4. CONCLUSIONS

Several relevant messages arise from this case report. First of all, it is important that stroke patients have a comprehensive diagnostic work‐up aimed to determine less common stroke causes, such as signs of vasculitis on intracranial vessel examinations or brain strokes involving different blood supply areas in younger patients. Second, syphilis should be taken into consideration as a potential cause of stroke that can be treated and thereby prevent further strokes. Third, prompt initiation of antimicrobial treatment slows down disease progression and induces regression of existing changes, thereby preventing further complications. Finally, regular patient follow‐up with laboratory tests and neuroradiological examinations provides a valuable overview of the treatment effect.

5. AUTHOR CONTRIBUTIONS

Davor Batinić: Conceptualization; data curation; formal analysis; investigation; methodology; supervision; writing – original draft; writing – review and editing. Ronald Antulov: Conceptualization; data curation; formal analysis; investigation; methodology; writing – original draft; writing – review and editing. Inge Klupka‐Sarić: Conceptualization; data curation; investigation; methodology; writing – original draft. Anita Ivanković: Conceptualization; data curation; investigation; methodology; writing – original draft. Renata Jurina: Conceptualization; data curation; investigation; methodology; writing – original draft. Marijana Karlović Vidaković: Conceptualization; data curation; formal analysis; investigation; methodology; writing – original draft. Ivana Talić Drlje: Conceptualization; data curation; formal analysis; investigation; methodology; writing – original draft. Jurica Arapović: Conceptualization; data curation; formal analysis; investigation; methodology; supervision; writing – original draft; writing – review and editing.

7. FUNDING INFORMATION

No funding or financial support was received for the study.

8. CONFLICT OF INTEREST STATEMENT

The authors declare that they have no conflicts of interest.

10. CONSENT

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Batinić D, Antulov R, Klupka‐Sarić I, et al. Cerebral infarction as initial manifestation of meningovascular neurosyphilis in an immunocompetent patient – A case report with long term follow‐up. Clin Case Rep. 2023;11:e7021. doi: 10.1002/ccr3.7021

9.1. DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analysed during the current study