Background

Syphilis is a common sexually transmitted infection (STI) caused by the spirochete bacterium Treponema pallidum. Syphilis is endemic in low/middle-income countries and incidence is increasing in developed countries over the past 20 years.1 2 Incidence is highest among individuals residing in endemic areas, men who have sex with men, sex workers and intravenous drug users.2 Concurrent human immunodeficiency virus (HIV) infection and other STIs are common. Clinical manifestations can be varied, making clinical recognition and diagnosis challenging. When detected, syphilis is effectively treated with penicillin with no known cases of documented resistance.2 We report a case of neurosyphilis presenting as multiple cranial neuropathies in an HIV-negative individual.

Case presentation

A 37-year-old woman presented with a 2-week history of progressive neurological complaints. Symptoms started with a sensation of disequilibrium and unsteadiness on her feet, and subsequently difficulty closing both eyes, right lip numbness, sequential bilateral hearing impairment (right, followed by left) and slurred speech. She denied limb weakness or numbness, headache, neck stiffness, photophobia, nausea, vomiting or visual changes. She also denied fever, rash, lymph node swelling or night sweats. She did note 10 kg weight loss in the few months prior to presentation in the context of recently diagnosed type 2 diabetes mellitus. She had since commenced metformin, gliclazide and dulaglutide which improved the diabetic control. Other comorbidities included morbid obesity (weight 96 kg, body mass index 40 kg/m²), asthma and eczema. She had not been taking steroids or immunosuppressant medication. She was born and raised in a subtropical region in Australia and denied significant travel history. She had been engaging in unprotected sex but denied intravenous drug use.

On the examination, there were bilateral cranial neuropathies involving trigeminal (V), abducens (VI), facial (VII), vestibulocochlear (VIII) and hypoglossal (XII) nerves. Lateral gaze was restricted bilaterally and there was bilateral upper and lower facial weakness with impaired eyebrow raise, eye closure and inability to smile. Weber’s test lateralised to the left ear and Rinne’s test demonstrated air conduction greater than bone bilaterally. Tongue was weak but midline on protrusion. Sensation was decreased to light touch and pinprick in V2 distribution on the right side. The remained of the neurological examination was unremarkable. There was no palpable lymphadenopathy or splenomegaly.

Investigations

Initial laboratory tests were consistent with mild inflammation; elevated C reactive protein of 12 mg/L (<10 mg/L), erythrocyte sedimentation rate 21 mm/hour (<12 mm/hour) and thrombocytosis of 447×10⁹/L (150–400 x 10⁹/L). The remainder of the full blood examination, renal function, electrolytes and liver function tests were unremarkable. Serum beta human chorionic gonadotropin was <1.2 IU/L and haemoglobin A1c was 8.7% (72 mmol/mol). Cerebrospinal fluid (CSF) examination demonstrated normal opening pressure of 13.5 cm H20 (10–25 cm H₂O), elevated protein of 1.28 g/L (<0.45 g/L) with normoglycaemia (CSF 3.8 mmol/L, serum 5.4 mmol/L) and lymphocyte predominant (76%) leucocytosis of 0.441×10ˆ9/L (<0.005×10ˆ9/L). Magnetic resonance imaging (MRI) scan of the brain with gadolinium demonstrated enhancement of the trigeminal nerve at the pons, as well as facial and vestibulochoclear nerves at the geniculate ganglion (figure 1A,B). There was no evidence of recent infarct or leptomeningeal enhancement. Contrast-enhanced MRI of the spine was unremarkable. Computed tomography (CT) scans of the neck, chest, abdomen and pelvis were negative for malignancy or lymphadenopathy. Serum T. pallidum particle agglutination assay (TPPA) and chemiluminescent microparticle immunoassay (CMIA) IgG and IgM were positive, with a rapid plasma reagin (RPR) titre of 1:32, consistent with active syphilis infection. Further CSF analysis showed positive TPPA, venereal disease research laboratory test (VDRL) titre of 1:8 and negative T. pallidum PCR. Workup for other infectious, autoimmune and neoplastic disorders was negative (table 1).

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Figure 1

Postcontrast enhancement of cranial nerves V, VII, VIII. A. Bilateral trigeminal nerves exiting pons, T1 Fast Spin Echo; B. facial and vestibulocochlear nerve at the geniculate ganglion, T1 Gradient Recall Echo.

Differential diagnosis

The differential diagnosis of multiple cranial neuropathies is broad. In this case, based on the clinical presentation of cranial neuropathy and ataxia, our initial working diagnosis was Miller-Fisher syndrome. This was rapidly revised to infectious (fungal, viral or atypical bacterial, eg, syphilis, tuberculous, borreliosis) autoimmune (sarcoid, behcet, systemic lupus erythematosis (SLE)) or malignancy (leptomeningeal carcinomatosis, lymphoma) when the CSF results were obtained. Further discussion on differential diagnoses for meningitis associated with cranial neuropathies can be found in table 2. Neurosyphilis was confirmed based on positive treponemal and non-treponemal tests on serum and CSF. Potential differentials of sarcoid, SLE, viral, fungal and atypical bacterial infections as well as malignancy were excluded or rendered less likely based on imaging, serology, PCR and pathology tests as outlined in table 1. Meningitic and meningovascular forms of syphilis were both considered. Despite the absence of leptomeningeal enhancement on MRI brain scan, given the widespread bilateral cranial neuropathies, lack of clinical seizures, marked CSF pleocytosis and radiological absence of stroke, early syphilitic meningitis was considered more likely.

Treatment

On further history, she denied a primary syphilitic chancre. During screening for concurrent STIs, Chlamydia trachomatis was detected on first-pass urine PCR.

Our patient was diagnosed with early syphilitic meningitis with multiple cranial neuropathies and commenced on intravenous benzylpenicillin 1.8 g 4 hourly according to local therapeutic guidelines (Electronic Therapeutic Guidelines, Australia) for a 15-day course. Given her comorbidies of poorly controlled diabetes and morbid obesity, a decision was made in consultation with the infectious diseases team not to treat prophylactically with steroid medication. Initiation of antibiotic treatment was closely monitored in the inpatient setting and she did not develop Jarisch Herxheimer reaction. Her cranial neuropathies improved dramatically by the eighth day of treatment. Concurrent chylamydia infection was treated with a 7-day course of 100 mg doxycycline two times per day.

Outcome and follow-up

The patient was discharged home to complete her course of antibiotic therapy. She is scheduled for outpatient review with the local infectious diseases team for serological monitoring of RPR titre and consideration of repeat CSF examination to confirm adequacy of neurosyphilis treatment.