Syphilis is a sexually transmitted infection caused by the spirochete Treponema pallidum. For 500 years, it has been a significant contributor to neurological damage. Syphilis cases have been rising in tandem with the human immunodeficiency virus (HIV) epidemic in recent years (3).
The term Neurosyphilis is used to characterize T. pallidum's direct invasion of the neurological system. It has long been believed that neurosyphilis is a late symptom of syphilis; however, studies have shown that it can occur during any stage of the disease. Different degrees of central neurological involvement can be categorized as either affecting the meninges, blood vessels, or the brain tissue itself. The bacterium T. pallidum can potentially invade each of these locations directly (1, 3).
Between 0.3–2.4% of all syphilis patients develop meningovascular syphilis (4). It appears to occur more often in relation to HIV, and several research studies indicate that the co-occurrence results in an accelerated advancement of a more severe type of neurosyphilis (3). However, there have also been numerous instances of syphilitic vasculitis (SV) in young, immunocompetent stroke patients (5, 6).
The meningovascular complications of syphilis occur due to a condition called focal syphilitic endarteritis. This condition is characterized by inflammation and fibrous changes in the outer layer of blood vessels, as well as the growth of fibroblasts in the inner layer and weakening of the middle layer. As a result, it leads to the formation of blood clots and reduced blood supply to the brain, causing ischemic infarction or tissue damage due to a lack of oxygen (1).
In 3% of all syphilis patients and 10% of neurosyphilis patients, the first symptom is a stroke (1). There have been multiple instances documented in medical literature where neurosyphilis has been observed to manifest as a stroke or a syndrome resembling a stroke (4).
In a case similar to ours, there was a case report that described a young man who initially presented with an ischemic stroke and was later diagnosed with both HIV and neurosyphilis (2). Similarly another case report described a patient with a comparable set of symptoms and clinical presentation with a significant presence of high-risk sexual behavior. Where Magnetic resonance imaging later revealed an area of subacute pons ischemia and partial thrombosis of the basilar artery with endarteritis (7). Additionally, there have been reports of several brainstem disorders linked to neurosyphilis (4). Furthermore, a singular case has been documented where a cerebral aneurysm resulting from syphilitic vasculopathy occluded in a patient with an aneurysm of the posterior communicating artery (8).
The magnitude and location of the infarction are related to the neurological impairments. Although the anterior circulation is more frequently affected, meningovascular syphilis can also affect the posterior circulation (4). Both CT and MRI can identify cerebral infarctions as tiny deep focal lesions. Cerebral infarctions in meningovascular syphilis are usually highly distinct due to the involvement of a single artery, in contrast to atherosclerotic cerebrovascular disease (9). There have been several reported cases of cerebral infarctions in the past. In the analysis of 14 new cases of meningovascular syphilis, 71% of the patients had cerebral infarction, which was present in two patients in multiple territories and in a deep region in 28% of all patients (10).
CSF abnormalities occurring in neurosyphilis include pleocytosis (45 WBC per high-power field), low glucose (< 2/3 serum glucose), and elevated protein (445 mg/dl). In up to 4% of patients with symptomatic neurosyphilis, CSF protein, glucose, and WBC count may be entirely normal, especially in advanced stages of the disease, such as in patients with tabes dorsalis (4). In the case presented here, the patient's CSF showed no pleocytosis.
When interpreting CSF results in HIV-positive and syphilis-positive individuals, care must be taken. Patients with HIV may exhibit a variety of CSF abnormalities, including an increase in CSF protein, WBC count (mostly lymphocytes), and immunoglobulin (both of intrathecal and extrathecal origin). Some have proposed a higher cutoff rate for CSF WBCs in the diagnosis of neurosyphilis, with 20 cells/ml being used in one study, as patients with HIV have been observed to have elevated WBC counts in their CSF attributable to HIV infection alone (4). In the absence of significant blood contamination of the CSF sample, a positive CSF VDRL or RPR test is regarded as indicative of neurosyphilis. The CSF VDRL test is extremely specific, even in situations when serum VDRL or RPR titers are high (up to 1:256). The results will yield a false-positive outcome only if there is sufficient blood contamination that affects the CSF (1).
The suggested treatment for patients with neurosyphilis or ocular syphilis consists of administering aqueous crystalline penicillin G at a daily dose of 18–24 million units. This can be given either through continuous infusion or in divided doses, and the treatment duration typically spans 10–14 days in our case. Alternatively, intramuscular (IM) procaine penicillin G with oral probenecid can be used (11). Ceftriaxone taken intramuscularly (IM) or intravenously (IV) is a suitable alternative therapy, According to the rates of complete clinical response at one month and serological response at six months, ceftriaxone was shown to be just as effective as the gold standard, benzylpenicillin, for the treatment of neurosyphilis (12).
Although parenteral penicillin G is generally recommended by treatment guidelines, our patient was treated with ceftriaxone IV as an alternative therapy due to the scarce availability of penicillin medications. Following that, the treatment was continued for an additional 3 weeks with benzathine penicillin G IM. Such therapy led to a virtual complete reversal of stenosed major intracranial arteries, which was evident on a late follow-up MRA done months after antimicrobial treatment (6).
Treatment for neurosyphilis is considered successful in patients when neurological symptoms improve, disappear, or stabilize, and CSF abnormalities return to normal. The CDC recommends patients to have another lumbar puncture every six months until the CSF WBC count returns to normal. Retreatment should be considered if the cell count has not dropped after six months or if the CSF cell count or protein is not normal after two years (11).
Additionally, there are no differences in the treatment of neurosyphilis between HIV-positive and non-HIV patients (4). However, it is important to note that HIV-positive patients with symptomatic neurosyphilis may have a higher likelihood of not responding to treatment, as determined by clinical and serological criteria. They may also face challenges in normalizing CSF abnormalities, even with adequate neurosyphilis treatment. As a result, routine follow-up with additional CSF testing is recommended for HIV-infected patients.