Neurosyphilis presenting as cranial nerve palsy, an entity which is easy to miss

Abstract

Neurosyphilis is a rare disease that until the 2000s was almost eradicated due to population awareness of HIV and efficient treatment. Since then, the prevalence of the entity is rising due to risk-associated behaviour such as unprotected intercourse. Neurosyphilis is still a difficult entity to diagnose especially when combined with acute HIV infection which can influence the usual clinical course of disease. In rare occasions, both acute HIV and early syphilis infection can present as mono or multiple cranial nerve palsies. This case demonstrates a rare manifestation of misdiagnosed early syphilis infection combined with acute HIV infection in a 34-year-old man with prior history of unprotected sex with men.

Background

Neurosyphilis is a rare disease that is rising in prevalence in the last decade due to risk-associated behaviour. Neurosyphilis is still a difficult entity to diagnose especially when combined with acute HIV infection. In rare occasions, syphilis infection can present as mono or multiple cranial nerve palsies. This case demonstrates a misdiagnosed early syphilis infection that initially presented as hearing loss followed by facial nerve palsy in a 34-year-old man with prior history of unprotected sex with men.

This case is important for the following reasons:

1. Since syphilis is a re-emerging entity, awareness is crucial for early diagnosis.

2. Syphilis should be in the differential diagnosis for patients at risk, with involvement of even a single cranial nerve.

Case presentation

A 34-year-old Caucasian man with no prior medical history developed a slight left-sided hearing impairment. Two months later, he developed left facial plegia, and was diagnosed with Ramsey Hunt syndrome. He was treated with oral prednisone 60 mg and acyclovir 200 mg for 10 days with improvement of left facial plegia but without significant change in hearing loss. A day following discontinuing steroidal treatment, left facial hemiplegia reoccurred, resulting in treatment renewal with prednisone 20 mg for additional 5 days without significant improvement.

On the fifth day of steroid treatment, he presented to our department due to the addition of acute right facial plegia combined with dysarthria and dizziness. Vital signs were in the normal range and neurological examination revealed a fully aware patient with dysarthria, bilateral facial plegia (more profound on the right side) and left hearing loss. The rest of his neurological examination was normal. Initial laboratory test results showed mild lymphocytosis and borderline C reactive protein (7 mg/dL, normal range <5 mg/dL).

Brain MRI showed slight diffuse enhancement of the facial and vestibulocochlear nerves complex, mainly on the left side (figure 1A) and enhancement of the left facial nerve on axial view (figure 1B). There was no evidence of pachymeningitis on MRI. Cerebrospinal fluid (CSF) analysis demonstrated normal glucose level, high protein level of 95 mg/dL (normal range <60 mg/dL) and lymphocytic pleocytosis with white blood cell count of 187×10^-6/L (85% mononuclear cells, normal range <5/μL). Blood test was positive for HIV antibody, which was confirmed with positive HIV PCR, with normal CD4 level. Further CSF and blood testing were positive for Treponema pallidum particle agglutination assay and Venereal Disease Research Laboratories, with titter level of 1:2 in blood and 1:1 in CSF. Intrathecal synthesis of oligo clonal bands was confirmed. Further investigations of patient’s CSF such as flow cytometry, cytology, PCR for herpes simplex virus 1, 2 and varicella zoster virus, tuberculosis testing (PCR, culture and Ziehl-Neelsen Stain), India ink for Cryptococcus, gram stain and culture, were all negative. Level of angiontensin converting enzyme were in the normal range of 36 U/L (normal range of 20–70) and Chest X-ray was normal. Based on these findings, a diagnosis of neurosyphilis was made and treatment was initiated with intravenous penicillin G at dose of 4 million units every 4 hours for 14 days with major improvement of facial bi-plegia and mild improvement of hearing loss. Treatment for chronic HIV infection was initiated on the day of discharge.

Figure 1.

Brain MRI. (A) Axial postgadolinium T1-weighted images showing slight diffuse enhancement of Left facial nerve (B) Coronal postgadolinium T1-weighted images showing slight diffuse enhancement of facial cochlear nerves complex (arrows).

Outcome and follow-up

A diagnosis of neurosyphilis was made and treatment was initiated with intravenous penicillin G at dose of 4 million units every 4 hours for 14 days with major improvement of facial bi-plegia and mild improvement of hearing loss on 6 months follow-up. Repeated CSF test revealed 4 white blood cells (normal range ≤5) with normal glucose (59 mg/dL) and protein (28 mg/dL). Repeated brain MRI was normal, and no enhancement was demonstrated. Treatment for chronic HIV infection was initiated on the day of discharge.

Discussion

We present a young man with subacute hearing loss and left facial drop that was initially diagnosed as Ramsey Hunt syndrome and only deterioration to bilateral facial plegia on steroidal treatment led to further investigation.

Bilateral facial nerve palsy is an exceedingly rare condition, accounting for less than 2% of all cases of facial palsy.¹ While facial mono-plegia, is usually idiopathic, facial bi-plegia usually has an inflammatory, infectious, neoplastic, traumatic or metabolic aetiology,.² Previously, it has been reported as a very rare presentation of acute HIV or syphilis infection,.^{3 4}

Syphilis is a sexually transmitted disease caused by the spirochete bacterium T. pallidum. With the advent of penicillin treatment and an aggressive public health approach, the annual incidence rate of syphilis in the USA decreased by about 95% between 1943 and 2000. Since 2000, however, the number of cases of syphilis infection in the USA has more than doubled,.⁵

An early symptomatic isolated neurosyphilis manifested as cranial nerve palsy is rare, with very few cases reported around the world in the last 40 years (table 1). The central nervous system may become involved during any stage of syphilis from several weeks to several years after the initial infection.⁶ While symptomatic neurosyphilis is most frequent after 2 years, syphilitic meningitis, the earliest manifestation of neurosyphilis, usually occurs less than 2 years following infection. However, early neurosyphilis is rarely diagnosed as most patients are asymptomatic, and therefore neurosyphilis is usually diagnosed in the tertiary stage.⁷

Table 1.

Reported cases of neurosyphilis with cranial nerves involvement as first presentation in the last 40 years

Study	Number of patients	Cranial nerve involvement
Li X et al 2017	1	Unilateral oculomotor nerve
Young AS et al 2017	1	Unilateral vestibulocochlear and facial nerve
Honorio GLF et al 2017	1	unilateral trigeminal nerve
Eda Kılıç Çoban et al 2016	1	Unilateral oculomotor. Bilateral trigeminal, facial, vestibulocochlear nerves
Maeda T et al 2015	1	Unilateral facial and Vestibulocochlear nerves
Park HI et al 2015	1	Unilateral Oculomotor Nerve
Ting et al 2015	1	Bilateral facial nerve
Alqahtani S 2014	1	Bilateral vestibulocochlear and facial nerves
Hong JH et al 2014	1	Trigeminal, facial and vestibulocochlear nerves
Klein TA et al 2014	1	Unilateral vagus nerve (left vocal cord paresis)
El Alaoui TK et al 2013	1	Unilateral trochlear nerve
Hess CW et al 2013	1	Unilateral Oculomotor Nerve
Jang JH et al 2012	2	A. Unilateral trigeminal nerve B. Unilateral oculomotor nerve
Hadrane L et al 2008	1	unilateral trigeminal nerve
Blok FA et al 2005	1	unilateral facial nerve
Takakura Y et al 2004	1	unilateral oculomotor nerve, trochlearis nerve and abducens nerve
Seeley WW et al 2004	1	Unilateral Oculomotor Nerve
Smith MM et al 2000	1	Bilateral Facial and Vestibulocochlear Nerves
Nunes da Silva MJ et al 2000	1	unilateral facial and Vestibulocochlear Nerves
Vogl T et al 1993	1	unilateral oculomotor nerve
Satoh J et al 1989	1	Unilateral facial and Vestibulocochlear Nerves
Betkowski A et al 1988	1	Unilateral vestibulocochlear nerves
Verduijn PG et al 1982	1	Unilateral facial nerve
Hungerbühler JP et al 1978	1	Unilateral vestibulocochlear nerves
Total	25	Oculomotor nerve—8 Trochlear nerve—2 Trigeminal nerve—5 Abducens nerve—1 Facial nerve—11 vestibulocochlear nerves—10 Vagus nerve—1

Patients with concomitant HIV and syphilis often present differently than syphilis patients without HIV. They may present with a more fulminant course, overlapping disease stages, multiple chancres, atypical skin rashes and a more rapid progression to neurosyphilis or like in our case as isolated neurosyphilis.^6–8 Interestingly, initially the patient reported improvement on steroidal regimen without penicillin. The benefit of steroidal treatment on ocular and otologic syphilis has been described.^{9 10} To our knowledge, there are no reports regarding improvement with steroids in other cranial nerve syphilitic involvement. It is possible that treatment with steroids in the acute phase may reduce the secondary inflammatory process which causes clinical improvement.

This case presents a misdiagnosis and delayed treatment of neurosyphilis. Due to potential neurological sequel that can be easily prevented, screening for neurosyphilis and HIV infection at health clinics and emergency departments, may be beneficial in patients at risk for sexually transmitted diseases that present with isolated (such as Bell’s palsy) as well as multi cranial nerve palsies.

Learning points.

• Syphilis is a re-emerging entity, awareness is crucial for early diagnosis.

• Patients with concomitant HIV and syphilis often present differently than syphilis patients without HIV.

• Further investigations are needed to examine the potential benefits of combined treatment with steroids and penicillin in acute neurosyphilis involving cranial nerves.

• Screening for neurosyphilis and HIV infection in patients at risk for sexually transmitted diseases that present with isolated cranial nerve palsy (such as Bell’s palsy) may be beneficial.