From the Department of Sexual Health and HIV, Whittall Street Clinic, University Hospitals Birmingham NHS Foundation Trust, Whittall Street, Birmingham, UK
The authors thank Rachael McGrath for the translation of the French paper by El Quessar et al. (J Neuroradiol. 2000; 27(3): 207:210).
Source of funding: Nil.
Conflict of interest: None declared.
Correspondence: Divya Dhasmana, MRCP, Department of Sexual Health and HIV, Whittall Street Clinic, University Hospitals Birmingham NHS Foundation Trust, Whittall Street, Birmingham, B6 4DH, United Kingdom. E-mail: email@example.com.
Received for publication December 16, 2012; and accepted April 11, 2013.
A 40-year-old Malawian gentleman presented with a 3-month history of progressive generalized headache, nausea, photophobia, lower backache (worse on coughing), and lower limb weakness (worse on the left than the right). For 1 month, he had increasing difficulty standing and, as a result, had become bed ridden. He denied any other symptoms.
In Malawi, aged 19 years, he had presented with genital ulceration and received treatment of syphilis with oral and parenteral antibiotics. He has no recall of follow-up to assess treatment.
Neurological examination demonstrated hypotonia of the lower limbs. Power in the legs was reduced bilaterally, predominantly distally, and mainly in the flexors, in the range of 1 to 4/5. Knee and ankle reflexes were absent bilaterally, and he had flexor plantar responses. There was reduced light touch sensation in his left leg at L3 to S1 with no saddle anesthesia. Rectal examination demonstrated good anal tone. Proprioception was intact. Vibration sense was not recorded. Romberg test and coordination of his legs could not be assessed because of leg weakness. The remainder of the general examination was unremarkable.
The differential diagnosis at this stage included primary central nervous system neoplasia, opportunistic infection secondary to HIV, granulomatous disease, or syphilitic infection.
Full blood count revealed a microcytic anemia, with a hemoglobin level of 13 g/dL (13.5–18 g/dL) and a mean corpuscular volume of 68.2 fL (80–99 fL). C-reactive protein and aspartate transferase were slightly elevated at 22 mg/L (reference value, <10 mg/L) and 48 U/L (reference value, 5–43 U/L), respectively, and remained so during his admission. Hemoglobin electrophoresis showed probable α-thallasemia. Other routine blood tests were normal.
Syphilis serology was requested and showed positive results (Table 1). Result of urine nucleic acid amplification test for chlamydia and gonorrhea was negative. Results of the investigation for autoimmune, paraneoplastic autoimmune, or vasculitic etiologies were negative. HIV test result was negative, as was serum cysticercosis immunoblot.
At lumbar puncture, the cerebrospinal fluid (CSF) was noted to be of a thick yellow appearance. Syphilis serology in the CSF was strongly suggestive of neurosyphilis (Table 1). Gram stain, India ink, and bacterial cultures were repeatedly negative on 3 occasions. Findings from viral polymerase chain reaction for herpes simplex types 1 and 2, varicella zoster, and enterovirus were negative. Findings from microscopy and culture for tuberculosis were also negative. There was no definite evidence of malignant cells in the CSF.
Findings from computed tomography of the thorax, abdomen, and pelvis were normal. Magnetic resonance imaging (MRI) revealed a mass lesion in the right cingulate gyrus of the frontal lobe of the brain (Fig. 1) and 3 further lesions of the spinal cord (Fig. 2). The remainder of the cord appeared normal.
Biopsy of the brain lesion showed nonspecific changes, but plasma cell infiltration suggestive of syphilis was noted. No specific treponemal staining or polymerase chain reactin was performed. There was no evidence of granulomatous lesions or malignancy. Findings from microscopy and culture for tuberculosis were negative.
Treatment of neurosyphilis with cerebral and spinal involvement was commenced with intravenous benzyl penicillin 24 MU daily: 4 MU every 4 hours for 17 days. Oral prednisolone 40 mg was also prescribed 24 hours before the start of penicillin and was continued for 3 days.
The patient showed a dramatic response with a reduction in lower back and left thigh pain, with clinical improvement in the distal power of ankle flexion to 3/5 over the 48 hours posttreatment. Cerebrospinal fluid and serological analysis after the completion of penicillin treatment at day 18 showed a 4-fold fall in rapid plasma reagin (RPR), consistent with effective syphilis treatment, with continued improvement at 7 months (Table 1). A repeat HIV test at this stage showed a negative result.
Repeat brain MRI 4 weeks after the completion of treatment showed a small area of cavitation at the site of the initial lesion (Fig. 3). Magnetic resonance imaging of the spine also demonstrated significant improvement, with resolution of the mass lesions (Fig. 4). Six weeks after the completion of treatment, the patient was able to walk independently, with some persisting weakness in both legs, more pronounced on the left. At 6-month follow-up, he described residual weakness of ankle flexion and extension only, grading 1/5.
The patient reported a monogamous relationship for 14 years. His wife was asymptomatic with no history of syphilis or other sexual partners. Her serology showed a Treponema pallidum particle agglutination of 1:5120 and an RPR of 1:32 with negative immunoglobulin M antibody, a pattern more in keeping with early syphilis, but also similar to her partner’s titers. In the absence of previous serology, she received treatment successfully for late latent syphilis. The couple has 2 healthy children in Malawi, for whom syphilis testing has been advised.
Clinical, serological, and histopathological features of the present case suggest neurosyphilis as the cause for the cerebral and spinal lesions. The radiological appearances strongly suggest the presence of syphilitic gummata at both neurological sites.
Syphilitic gumma is a pathognomonic feature of tertiary syphilis and is believed to evolve from untreated or inadequately treated syphilis. This gentleman’s sexual history is in keeping with the development of tertiary syphilis.
Gummata are granulomatous lesions triggered by a hypersensitivity reaction to the spirochete. They typically have a gum-like necrotic core, surrounded by epitheloid cells, lymphocytes, and Langhans giant cells, and are characterized by an abundance of plasma cells and by vascular endothelial proliferation.
Bramwell,1 in 1888, considered syphilitic gummata to be the most common form of cerebral tumors in adults. With improved diagnosis and increased use of antibiotics for treatment of syphilis and other infections, gummata have become increasingly rare. In 2009, Fargen et al.2 conducted a literature search and found 156 previous cases of reported isolated cerebral gummata and described their clinical and radiological appearances in detail. There have been 8 published case reports of cerebral syphilitic gummata in the last 10 years.3–10
A literature search revealed 3 published reports of spinal cord gummata, of which it was possible to obtain 1.11 A 25-year-old HIV-negative woman had an intramedullary nodular lesion at C3 detected at MRI, which was biopsied and confirmed syphilis, although there is no clarification on the latter. Marked improvement of the lesion was noted at 1 month after treatment, which is similar to the observations made in the present case.
This patient who presented 21 years after an initial presentation of syphilis, possibly incompletely treated or reinfected after initial treatment, presented with signs of a radiculopathy and lower motor neurone lesions. The cerebral lesion caused no apparent symptoms apart from headaches. The CSF demonstrated significant evidence of inflammation with high protein and lymphocyte titers consistent with neurosyphilis. Magnetic resonance imaging demonstrated evidence of 4 mass lesions of the central nervous system, which resolved 4 weeks after treatment. No other etiological agent or process was noted. Clinical improvement occurred rapidly at first, possibly because of a reduction of edema secondary to steroids, and then more slowly over several weeks, possibly because of a combination of reversible ischemia and resolution of gummatous tissue.
We have presented a very unusual case of a 40-year-old HIV-negative Malawian gentleman with clinical features in keeping with concurrent intracerebral and spinal cord syphilitic gummata, which showed remarkable response to treatment of neurosyphilis. It illustrates that gummatous disease can be a potentially reversible condition compared with other manifestations of tertiary syphilis, and failure to diagnose it can be associated with considerable morbidity and mortality.
1. Bramwell B. Intracranial Tumors. Edinburgh: Y.J. Pentland, 1888.
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4. Lee CW, Lim MJ, Son D. A case of cerebral gumma presenting as brain tumor in a human immunodeficiency virus (HIV)–negative patient. Yonsei Med J 2009; 50: 284–288. doi:10.3349/ymj.2009.50.2.284
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11. El Quessar A, El Hassani R, Chakir N, et al. Syphilitic spinal cord gumma. J Neuroradiol 2000; 27: 207–210. Article in French.