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Table of Contents    
BRIEF REPORT
Year : 2020  |  Volume : 68  |  Issue : 4  |  Page : 889-893

Neurosyphilis - A Forgotten Disease: Case Reports with Ten Years Follow-Up and Review of Literature


1 Department of Neurology, Fortis Escorts Hospital, Malviya Nagar, Jaipur, Rajasthan, India
2 Department of Radiodiagnosis, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India

Date of Web Publication26-Aug-2020

Correspondence Address:
Dr. Neetu Ramrakhiani
Department of Neurology, Fortis Escorts Hospital, JLN Marg, Malviya Nagar, Jaipur - 302 017 Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.293488

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 » Abstract 


Neurosyphilis is a rare disease. We describe two patients of neurosyphilis with their clinical course and long-term follow-up. Our first patient was a 47-year-old male who presented with ataxia, headache, papilledema, sensorineural hearing loss, and myelopathy. Investigations revealed pachymeningitis and cervicodorsal myelitis. Cerebrospinal fluid (CSF) was reactive with positive CSF Venereal Disease Research Laboratory (VDRL) and blood Treponema pallidum hemagglutination (TPHA). His clinical, laboratory, radiological findings, and follow-up of the last 10 years are discussed with serial imaging. Case 2 was a 61-year-old male, who presented with neuropsychiatric symptoms, which resolved with treatment. We have reviewed the Indian case reports of this disease. It is easy to confuse neurosyphilis with tubercular meningitis in an Indian setting. The role of steroids in myelitic form has also been discussed. Worldwide reported cases of syphilitic myelitis are tabulated with their outcomes.


Keywords: Deafness, neurosyphilis, neuropsychiatric features, pachymeningitis
Key Messages: Neurosyphilis although very rare in today's era should continue to be in our list of differential diagnoses in appropriate clinical settings.


How to cite this article:
Ramrakhiani N, Sukhani PK, Dubey R. Neurosyphilis - A Forgotten Disease: Case Reports with Ten Years Follow-Up and Review of Literature. Neurol India 2020;68:889-93

How to cite this URL:
Ramrakhiani N, Sukhani PK, Dubey R. Neurosyphilis - A Forgotten Disease: Case Reports with Ten Years Follow-Up and Review of Literature. Neurol India [serial online] 2020 [cited 2020 Sep 25];68:889-93. Available from: http://www.neurologyindia.com/text.asp?2020/68/4/889/293488




Neurosyphilis is a rare disease that is seen on an infrequent basis in today's antibiotic era. Spinal cord involvement and pachymeningitis are very rare presentations of this uncommon disease. We report two such cases with follow-up of nearly 10 years in one patient.

Case 1

A 47-year-old male first presented in 2008 with low-grade fever and sensorineural deafness in the right ear for which he underwent stapedectomy without benefit. He was a diabetic, non-smoker, without any history of drug or alcohol abuse. One and a half months later he developed headache, diplopia, and imbalance on walking and paraesthesia on neck flexion. He gave a history of unprotected intercourse with commercial sex workers two years previously. On examination, he had normal memory, pupils showed normal response to light and accommodation. Bilateral papilledema with bilateral sixth and right eighth nerve palsies were present. Lower limbs revealed asymmetrical, predominantly proximal weakness right more than left with hypertonia and extensor plantar responses, sensory level to pinprick at D-10 and impaired in lower limb proprioception. His cerebrospinal fluid (CSF) testing done outside had revealed lymphocytic meningitis [Table 1]. Blood Venereal Disease Research Laboratory (VDRL) and Treponema palladium hemagglutination (TPHA) were found to be positive. Test for antinuclear antibody (ANA), cytoplasmic antineutrophil antibodies (C- ANCA), perinuclear antineutrophil cytoplasmic antibodies (P-ANCA), brucella, and human immunodeficiency virus (HIV) were negative. High resolution computed tomography (HRCT) of the chest was done to exclude alternative causes like tuberculosis, sarcoidosis, and granulomatosis with polyangiitis (GPA). Contrast-enhanced magnetic resonance imaging (CEMRI) of brain and spine revealed leptomeningeal enhancement in the cervicodorsal cord [Figure 1]a and intense dural enhancement/pachymeningitis in the posterior fossa [Figure 2]a and [Figure 2]b. The patient was started on crystalline penicillin and steroids. Echocardiography was done to rule out aortitis. Serial CSF examinations were done till his CSF became acellular and VDRL became negative with near-complete improvement in his power and 60% improvement in his hearing. His magnetic resonance imaging (MRI) cervicodorsal spine done in 2009 showed a reduction in meningeal enhancement [Figure 1]b. He continued to be on annual follow-up for the next 7 years. In 2013 June, he developed headache with severe neck pain, difficulty in walking, bilateral hearing difficulty with the reappearance of pyramidal signs. Neuroimaging revealed significant meningeal enhancement posterior to clivus extending till foramen magnum and cervical cord [Figure 1]c and [Figure 3]a. Repeat CSF showed increased cellularity [Table 1]. He was given a course of ceftriaxone (2 weeks), doxycycline, and low dose of dexamethasone (6 weeks). Two months later, he developed left vocal cord palsy and marked worsening of hearing in the right ear with diffuse pachymeningitis. Meningeal biopsy was refused by the patient. The patient was maintained on corticosteroids and immunosuppressants (methotrexate) till 2015. Follow-up MRI spine [Figure 1]d and brain [Figure 3]b scan showed significant resolution of meningeal thickening when steroids were reduced and stopped. He had waxing waning of symptoms for one year till 2015 with pachymeningeal thickening with enhancement and extrinsic compression of cervical cord C2-3/3-4 [Figure 1]e. Steroid dosage was increased followed by gradual tapering. No fresh episode has been recorded in the last 5 years and the patient continues to be on maintenance steroids and immunosuppressants.
Table 1: Serial CSF reports of case 1

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Figure 1: (a) 20/9/2008 sagittal post contrast MRI scan shows thick meningeal enhancement along surface of cervicodorsal cord. (b) 25/2/2009 sagittal post contrast T1 MRI scan shows reduction in meningeal enhancement. (c) sagittal T2 scan 23/7/2013 showing hypointense meningeal thickening. (d) follow up scan sagittal T2 2/7/2015 showing significant resolution of meningeal thickening after treatment. (e) post contrast T1 images on 22/8/2015 reappearance of meningeal thickening and enhancement causing cord compression

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Figure 2: (a) axial post contrast- T1 MRI showed enhancement along right 7,8th nerve complexes and cochlea, (b) 20/9/2008, axial post contrast T1 MRI showed thick meningeal enhancement along posterior fossa convexity aspects

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Figure 3: (a) 23/7/2013- sagittal post contrast T1 MRI Brain Images showing enhancement along clivus with thick enhancement extending up to foramen magnum. (b) sagittal post contrast T1 MRI showing significant resolution of meningeal enhancement in follow up scan dated 2/7/2015

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Case 2

Patient aged 61 years old, ex-serviceman presented in 2009 with decreased appetite, fever, and change in behavior for 15 days. The patient started muttering to self, had slurred speech, visual hallucinations with picking behavior, change in sleep-wake cycle, bladder bowel incontinence, and imbalance while walking. The patient was a chronic smoker, had a history of social drinking and no history of substance abuse. There was no history of myoclonic jerks, seizures, or any episode of cognitive or behavioral problems prior to this episode. HIV 1 and 2 were non-reactive. Blood VDRL and TPHA were positive. On admission, patient's mini-mental state examination (MMSE) was 11. MRI brain revealed gliotic areas in periventricular white matter and frontal subcortical white matter. Electroencephalogram (EEG) and metabolic parameters were normal. CSF examination had lymphocytic meningitis with raised proteins, positive CSF VDRL, and negative Ziehl–Neelsen staining for acid-fast bacilli, KOH (Fungal stains), and gram stain [Table 2]. ANA, c ANCA, p-ANCA were negative and ACE/TSH/antithyroid antibodies were found to be within normal limits. Contrast-enhanced computed tomography (CECT) chest was unremarkable. He was treated with ceftriaxone and benzathine penicillin and had good improvement in cognitive function. One-week later CSF examination was repeated [Table 2]. On follow-up after three months, repeat MMSE score was 22/30 with 2-point loss each in orientation, recall, copying, and writing.
Table 2: Serial CSF reports of case 2

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Review of literature

Neurosyphilis is caused by infection of the central nervous system by Treponema Pallidum. It is usually seen in association with HIV infection with low CD4 + counts. It can be subclassified into early and late neurosyphilis. Early neurosyphilis usually involves the meninges, CSF, and vasculature. It includes asymptomatic neurosyphilis, symptomatic meningitis, and meningovascular syphilis. Late neurosyphilis involves the brain and spinal cord. It includes general paresis and tabes dorsalis. Blood tests for syphilis can be classified into treponemal and nontreponemal tests. Rapid plasma reagin and VDRL test is a non-treponemal test. They are used for initial screening and subsequent follow-up. VDRL test remains positive indefinitely in tertiary syphilis. Blood VDRL can be falsely positive in conditions like malignancy, autoimmune disease, malaria, and non-venereal treponemal infections like yaws and pinta. Treponemal tests like FTA-ABS carry a high degree of sensitivity and specificity in secondary, latent, tertiary, and quaternary syphilis. [Table 3] reveals Indian case reports with the diagnosis of neurosyphilis. The largest Series was by Srinivasan et al[1] with more than 100 cases of neurosyphilis. [Table 4] reveals the worldwide reported cases of syphilis meningomyelitis, clinical details, treatment, and their outcome.
Table 3: Indian case reports of Neurosyphilis

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Table 4: Reported cases of syphilitic myelitis

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Neurosyphilis is defined as a CSF white blood cell (WBC) count of 20 cells/microliter or greater and/or a reactive CSF VDRL test result, and/or a positive CSF intrathecal T. pallidum antibody index.[24] There are very few false-positive causes for CSF VDRL unless the CSF sample is contaminated by blood, unlike positive blood VDRL which can be positive in other diseases.[25] The interpretation of CSF VDRL is quite complex. It is a test that has very high specificity although it has low sensitivity. It may be absent in late stages.[26]


 » Discussion Top


Case 1 is very unusual with clinical manifestation of meningomyelitis/pachymeningitis as a presentation of neurosyphilis. Ten years follow-up with serial radiology imaging has not been described so far. Confusion with tubercular meningitis is common as the latter is far more common in the Indian subcontinent. Otosyphilis although well described in syphilis literature is not well recognized.[23] Ear can also continue to be the reservoir for infection after the treatment of initial meningitis.

Patient two presented with a meningeal form of syphilis with neuropsychiatric manifestations, positive CSF VDRL, and had significant improvement after treatment. A high index of suspicion toward this rare disease would help in diagnosis. A statement by Stokes[27] in his 1944 text said, “The frequency of neurosyphilis in general medical practice depends to a large extent on the thoroughness of the search for signs of neuraxis involvement and the frequency with which the spinal fluid examination is employed”. This statement remains true till date.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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Matijisaitis V, Vaitkus A, Pauza V, Valiukeviciene S, Gleizniene R. Neurosyphilis manifesting as transverse myelitis. Medicina (Kaunas) 2006;42:401-5.  Back to cited text no. 14
    
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Chilver-Stainer L, Fischer U, Hauf M, Fux CA, Sturzenegger M. Syphilitic myelitis: Rare, nonspecific, but treatable. Neurology 2009;72:673-5.  Back to cited text no. 15
    
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Lee CB, Choi SM, Kim SJ, Chae BG, Kim JH, Jin SS, et al. A case of acute transverse myelitis associated with neurosyphilis. Infect Chemother 2012;44:446-9.  Back to cited text no. 18
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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