Neurosyphilis

Original Editor - User: Mahnoor Zubair
Top Contributors - Khloud Shreif, Mahnoor Zubair, Kim Jackson and Ewa Jaraczewska

Introduction

Neurosyphilis is caused by the bacterium “Treponema pallidum” subspecies pallidum (T. pallidum), which invades the central nervous system (CNS) early in the infection. CNS involvement often occurs when the infection is in its primary stage, when the initial sore, or chancre (an ulcer or sore, it begins at the entry point of Treponema pallidum, the bacterium that causes syphilis, into the body in the primary stage of syphilis) appears.

Although syphilis is essentially a sexually transmitted disease, it can invade the brain and spinal cord with accompanying tissue, leading to neurosyphilis if it is not treated. Most patients acquire an intense immune response that successfully eliminates the bacterial infection from the CNS, preventing complications over time. A percentage of patients either fail to eradicate the bacteria completely from their CNS or are recurrently invaded by the pathogens. This can lead to neurosyphilis presentations either asymptomatic or symptomatic and happens weeks, months, or even years after the primary infection.

The following video provides an easy understanding of the concept of Neurosyphilis.

Types and Clinical Presentation of Neurosyphilis

Neurosyphilis can be varied since its presentation will depend on at what stage of the infection it occurs and what parts of the CNS the infection has affected.

The four main neurosyphilis types are as follows:

1. Asymptomatic Neurosyphilis (ANS)

Asymptomatic neurosyphilis is an abnormality of the CSF which is in accordance with neurosyphilis in a patient with serological evidence of syphilis but without any neurological signs. Although such neurosyphilis may occur in early and latent syphilis, the incidence declines with the duration of infection. Such patients are asymptomatic but show certain abnormalities in CSF, such as increased white blood count or protein.

Key features:

• No neurological symptoms.
• CSF abnormalities.
• Can occur in both early and latent syphilis.

2. Early Symptomatic Neurosyphilis

Early symptomatic neurosyphilis typically manifests during the first 12 months of infection, primarily by inflammation of the meninges. This condition exhibits all of the classic symptoms of meningitis, including headaches, nausea, vomiting, photophobia or sensitivity to light, and cranial nerve palsies. Seizure can also develop if it becomes a serious condition. While this occurs in very large numbers of cases as part of an early infection, its pre-HIV serum diagnosis was rarely made.

Key features:

• Early onset (within 12 months of infection).
• Symptoms of meningitis (e.g., headache, photophobia, nausea)
• Cranial nerve involvement and potential seizures.

3. Meningovascular Syphilis

Meningovascular syphilis is by inflammation of the vessels within the CNS, resulting in endarteritis, or inflammation of the inner walls of the artery. This disease more commonly produces thrombosis and subsequent infarction and can present symptomatically as a stroke. It appears 5-12 years after infection has occurred and may affect any blood vessel in the cerebral or spinal cord.

Key features:

• Typically occurs 5-12 years after infection.
• Endarteritis of CNS vessels.
• Stroke-like symptoms due to vessel blockage and infarction.

4. Parenchymatous Syphilis

Parenchymatous syphilis refers to damage within the brain tissue itself and includes two major subtypes:

Paretic Neurosyphilis

This form presents a wide variety of neuropsychiatric symptoms. Early signs include irritability, forgetfulness, personality changes, and headache. In its later stages, it causes emotional instability, impaired judgment, memory loss, confusion, as well as severe psychiatric disturbances such as depression, hallucinations, or psychosis. It could start slowly or abruptly.

Tabetic Neurosyphilis (Tabes Dorsalis)

In Tabes Dorsalis, damage occurs to the dorsal columns of the spinal cord and the posterior roots and results in severe loss of sensation. Inability to walk properly; lightning pains, which are sharp pains, sudden, and transient; paresthesia or tingling sensations; dysfunction of the bladder; visual impairment due to optic atrophy. Diminished reflexes, loss of vibratory sense, and characteristic Argyll Robertson pupils which accommodate but do not react to light.

Key features:

• General paresis: Cognitive decline, personality changes, psychiatric symptoms.
• Tabes dorsalis: Sensory loss, unsteady gait, bladder dysfunction, optic atrophy.

Epidemiology

The epidemiology of neurosyphilis parallels closely that of syphilis in general. Cases decreased dramatically in the early 1950s, primarily as a result of enhanced public health programs and the ready availability of antibiotics. The incidence then started to increase with the advent of the AIDS pandemic, when HIV coinfection enhanced the progression of neurosyphilis. With increased awareness and adoption of safe sex, rates have been erratic but tend generally to keep pace with syphilis transmission.

Diagnostic Procedures

Clinical, serologic, and cerebrospinal fluid (CSF) findings are used in diagnosing symptomatic neurosyphilis. In contrast, asymptomatic neurosyphilis is diagnosed based on serologic tests and CSF abnormalities in the absence of clinical symptoms.

Serologic Testing

There are two kinds of serologic tests used in diagnosing syphilis: nontreponemal and treponemal tests. Nontreponemal tests include those antibody measurements against cardiolipin, which are not specific to Treponema pallidum and may result in false positives if due to other causes. Treponemal tests detect the specific antibodies developed as a response to the infection by Treponema pallidum, hence, more precisely for syphilis.

According to one study, a proper diagnosis of neurosyphilis (NS) requires an overall assessment that takes into consideration clinical and biological factors. PCR and serological tests and Venereal Disease Research Laboratory (VDRL) testing along with immunoblot analysis are applied on cerebrospinal fluid samples.

Cerebrospinal fluid Pleocytosis

The CSF pleocytosis in syphilis is dominated by lymphocytes. During acute syphilitic meningitis, polymorphonuclear lymphocytes also may be predominant. Traditionally, ≥5 cells/mL has been the threshold defining pleocytosis. However, the specificity of this threshold is lower in co-infected patients with HIV, because the abnormalities caused by the HIV infection themselves are nonspecific. Emerging evidence suggests that increasing the cutoff to 10 cells/mL for HIV-positive patients on antiretroviral therapy, and to 20 cells/mL for patients not on such therapy, may increase the specificity of the diagnosis for neurosyphilis.

PCR Assays

Although the advent of PCR has indeed improved significantly the diagnosis of early syphilis, CSF serological tests are still used most often to diagnose neurosyphilis. According to a meta-analysis of several studies, PCR had a sensitivity of 40 to 70% for definite neurosyphilis, with specificity varying between 60 and 100%. The most commonly used PCR test was for the Tp47 gene, which had a combined sensitivity of 68% and a specificity of 91.9%. In contrast to PCR, the respective CSF serology tests were found to be more sensitive than PCR.

Neuroimaging

Neuroimaging is very important in identifying abnormalities in the brain or spinal cord of patients with neurosyphilis. It forms an integral part of diagnosis, treatment, and continued follow-up of such patients.

Neuroimaging results are variable with the stage of the disease and usually not pathognomonic. Most symptomatic patients have either normal neuroimaging results or only slight abnormalities, which adds up to the need for a high index of suspicion for proper and early diagnosis, and, therefore, for awareness on the part of the clinicians about this condition.

Treatment

Intravenous penicillin G is the treatment of choice for all types of neurosyphilis and syphilitic eye disease. If patient adherence can be guaranteed, an outpatient regimen is intramuscular benzathine penicillin with oral probenecid. Newer agents that attain high cerebrospinal fluid levels, such as ceftriaxone or azithromycin, have not been studied adequately for neurosyphilis. Syphilis infection enhances the ability of the HIV virus to be transmitted; conversely, HIV increases the chance of acquiring syphilis, so all patients diagnosed with syphilis should be offered HIV testing.

In general, a course of 14 days with intravenous penicillin or ceftriaxone is recommended. Therapeutic response can be evaluated by the following criteria: clinical findings, serum VDRL levels, and CSF cell count.

The CDC recommends three weekly injections of benzathine penicillin at doses of 2.4 million units per injection as the treatment regimen for neurosyphilis. These are expected to halt progression of asymptomatic disease and eradicate active disease, although neurologic abnormalities are likely to continue evolving because of premorbid CNS damage.

Role of Physiotherapy

Physiotherapy intervention for neurosyphilis is more related to symptomatic management along with prognostic improvement in cases where there are neurological impairments.

There is not much evidence that physical therapy could be used effectively in managing symptoms or improving quality of life, but some case studies on patients who have received physical therapy and rehabilitation protocols along with medication showed considerable improvement.

Some ways Physiotherapy can play its role in:

Neuromuscular Re-education Techniques: To enhance coordination, balance and proprioception, especially for patients with gait disturbances.

Strength Training: Exercises to strengthen affected muscle groups and strengthen the overall muscle tone, thereby improving mobility and stability.

Range of Motion Exercises: Passive or active exercises to maintain or improve joint flexibility and minimize stiffness.

Pain Management: Modalities such as heat, cold, or electrical stimulation may be helpful to manage the pain associated with the neurological symptoms.

Postural Training: Education to a patient on proper posture and body mechanics to prevent further injury and improvement in function.

Functional Training: Activities designed to promote improvement in everyday activities, mobility, and increased independence of the individual.

Education and Counseling: Providing information about the condition, self-management strategies, and the importance of adherence to medical treatment.

Multidisciplinary Approach: Consultation with other healthcare professionals, such as neurologists and occupational therapists, to gather all disciplines and create a comprehensive treatment plan.

The treatment plan should vary according to the individual's specific symptoms and needs, taking into consideration the severity of the condition and whether other health issues exist.