EMERGENCY:A young person with stroke symptoms, unexplained dementia, severe shooting limb pains, or acute meningitis where syphilis serology has not been checked —call040-46324365immediately — 24 hours, 7 days— 24/7
Neurosyphilis in Hyderabad: The Great Neurological Mimic That Returns — Diagnosed With a Blood Test, Cured With Penicillin
Expert assessment of the five forms of neurosyphilis — asymptomatic, meningeal, meningovascular, general paresis, and tabes dorsalis — with VDRL/TPHA serology, CSF VDRL/TPHA, MRI brain, and IV benzylpenicillin G 18–24 million units/day for 10–14 days as the gold-standard treatment at KIMS Neuroscience, Secunderabad, Hyderabad.
Neurosyphilis is CNS invasion by Treponema pallidum in untreated or inadequately treated syphilis. Five clinical forms: asymptomatic (CSF abnormalities only); meningeal (1–2 years after primary; headache, fever, CN palsies); meningovascular (5–10 years; stroke in a young person from obliterative endarteritis); general paresis/GPI (10–20 years; progressive dementia, personality change, grandiosity, tremor, Argyll Robertson pupils); and tabes dorsalis (10–30 years; lancinating pains, sensory ataxia, areflexia, Charcot joints, AR pupils). The Argyll Robertson pupil (small, irregular, accommodates but does NOT react to light) is pathognomonic of neurosyphilis affecting the midbrain. Treatment: IV benzylpenicillin G 18–24 million units/day for 10–14 days — the only treatment proven to achieve treponemicidal CSF levels. Syphilis is re-emerging in India; syphilis serology should be checked in ANY unexplained neurological presentation in a person under 60.
- The Argyll Robertson pupil
- Small, irregular, accommodates (near response preserved) but does NOT react to light. One of the most specific neurological signs in all of medicine. Found in late neurosyphilis affecting the Edinger-Westphal nucleus + pretectal nuclei. Never attribute small pupils to ageing, glaucoma, or diabetes without checking syphilis serology.
- Check syphilis serology in any unexplained neurology
- VDRL + TPHA in any: unexplained dementia under 60, young-onset stroke without conventional risk factors, unexplained meningitis, unexplained CN palsy, psychiatric symptoms in a young adult. Neurosyphilis is treatable. Missing it is unforgivable.
- Five forms with timelines
- Asymptomatic (months–years) · Meningeal (within 1–2 years): headache, CN VI/VII/VIII palsies · Meningovascular (5–10 years): stroke-like in young person with weeks of prodrome · GPI (10–20 years): dementia, grandiosity, tremor · Tabes dorsalis (10–30 years): lancinating pains, sensory ataxia, Charcot joints
- IV penicillin ONLY — oral does not work
- IV benzylpenicillin G 18–24 million units/day for 10–14 days. Oral penicillin does NOT achieve adequate CNS levels. Not a lower-dose alternative. Not a 7-day course. The full IV protocol is the only treatment with proven evidence.
- Jarisch-Herxheimer reaction
- Within 6–12 hours of first penicillin dose, ~25–30% develop fever, rigors, hypotension, and transiently worsening neurological symptoms. Self-limiting (12–24 hours). Managed with paracetamol + IV fluids + observation. Anticipate and monitor for all neurosyphilis patients.
- HIV co-infection changes the rules
- HIV significantly increases risk of neurosyphilis. High-titre VDRL (≥32) in any HIV-positive person: LP mandatory regardless of neurological symptoms. Serology may be false-negative at very high HIV titres (prozone phenomenon).
- Post-treatment monitoring
- CSF re-examined at 6 months: cell count should normalize (less than 5 cells/mm3) · Serum VDRL/RPR titre should decline 4-fold by 6–12 months · TPHA/FTA-ABS remain reactive lifelong: NOT a monitoring test
| Fact | Details |
|---|---|
| Five forms | Asymptomatic (CSF only) · Meningeal (CN palsies) · Meningovascular (young stroke) · GPI (progressive dementia) · Tabes dorsalis (lancinating pains + sensory ataxia) · All treatable with IV penicillin |
| Argyll Robertson pupil | Small + irregular + accommodates + does NOT react to light = pathognomonic neurosyphilis · Midbrain Edinger-Westphal nucleus + pretectal nuclei damage |
| Serology | Screening: VDRL or RPR (non-treponemal, declines with treatment, use for monitoring) · Confirmation: TPHA or FTA-ABS (treponemal, remains reactive lifelong) · CSF VDRL reactive = diagnostic |
| Treatment | IV benzylpenicillin G 18–24 million units/day for 10–14 days · Only proven treatment · Oral penicillin inadequate · Then IM benzathine penicillin G weekly x3 as consolidation |
| Jarisch-Herxheimer | 25–30% within 6–12 hours · Fever + rigors + hypotension + transient neurological worsening · Self-limiting 12–24 hours · Paracetamol + IV fluids + observation |
| HIV co-infection | LP mandatory in HIV+ with VDRL ≥32 · Neurosyphilis can occur earlier and present atypically · False-negative serology risk · Co-test HIV in all neurosyphilis patients |
| Post-treatment CSF | Re-examine CSF at 6 months · Cell count normalises within 6 months if treatment effective · Failure to normalise = retreatment · TPHA remains reactive lifelong (cannot use to monitor) |
About This Condition
Neurosyphilis at a Glance
The essential facts that shape how neurosyphilis is recognised, diagnosed, and treated at KIMS — from its definition as the great neurological mimic and its re-emergence in India, through the diagnostic rule of checking syphilis serology in any unexplained neurological presentation, to the IV benzylpenicillin gold-standard treatment.
What it is
Neurosyphilis refers to infection of the central nervous system by Treponema pallidum, the bacterium that causes syphilis. It occurs when inadequately treated or untreated syphilis disseminates to the brain and spinal cord. Neurosyphilis can occur at any stage of syphilis — even in the early weeks after primary infection (early neurosyphilis) or decades later (late neurosyphilis producing dementia or tabes dorsalis). It is one of the great mimics in neurology, capable of presenting as meningitis, stroke, dementia, psychosis, or spinal cord disease.
Re-emerging in India
Syphilis incidence is increasing globally, including in India, driven by changing sexual behaviour, reduced condom use, and inadequate syphilis screening in antenatal and general health settings. The NACO (National AIDS Control Organisation) surveillance data shows syphilis prevalence of 0.3–1% in India’s general population and higher rates in high-risk groups. As syphilis rates rise, neurosyphilis presentations — which occur after inadequate or absent syphilis treatment — are increasing in neurology clinics across India including at KIMS.
The diagnostic rule
Syphilis serology (VDRL or RPR for screening; TPHA or FTA-ABS for confirmation) should be checked in ANY unexplained neurological presentation — particularly unexplained dementia in a person under 60, young-onset stroke, unexplained meningitis, psychiatric symptoms in a young adult, or acute cranial nerve palsy. Neurosyphilis is entirely treatable with IV penicillin, but permanent neurological damage accumulates the longer treatment is delayed.
Treatment
IV benzylpenicillin G 18–24 million units per day (3–4 million units every 4 hours) for 10–14 days. This is the only proven treatment for neurosyphilis. Oral penicillin does not achieve adequate CNS levels. Doxycycline is an alternative for penicillin-allergic patients but has lower evidence. After IV penicillin, IM benzathine penicillin G 2.4 million units once weekly for 3 weeks is given as consolidation.
Emergency
040-46324365
Appointment
040-44885000
Dementia in a 38-Year-Old
A 38-year-old man is brought to KIMS by his family because his behaviour and thinking have deteriorated over the past 8 months. He was a functioning professional; now he is forgetful, disinhibited, making poor decisions, and has developed grandiose beliefs — claiming to be exceptionally wealthy and important, making inappropriate financial decisions. His family thought it was a psychiatric condition and had him assessed by a psychiatrist, who started antipsychotic medications with no improvement.
At KIMS, the neurological examination adds important findings: mild tremor of the hands and tongue, dysarthria (slurred speech), and abnormal pupils. The pupils are small and irregular, react to accommodation (near response is preserved) but not to light. This is the Argyll Robertson pupil — one of the most specific neurological signs in all of medicine, pathognomonic of neurosyphilis affecting the midbrain. MRI brain shows frontal and temporal cortical atrophy. VDRL is sent.
VDRL returns reactive at 1:64. TPHA is strongly reactive. CSF VDRL is reactive, CSF TPHA reactive, CSF shows 42 lymphocytes and protein 0.9 g/L. Diagnosis: general paresis of the insane (GPI) — the parenchymatous form of neurosyphilis producing progressive dementia from treponema invasion of the brain parenchyma.
IV benzylpenicillin 4 million units every 4 hours for 14 days is started. The family are counselled that the dementia will not reverse — but that progression will be arrested. Partners are notified and screened. This man’s primary syphilis occurred years earlier and was either unrecognised or inadequately treated. He has been harbouring active neurosyphilis for the past decade.
Book a Consultation
Speak directly with our neurosyphilis specialist team — neurology, infectious diseases, and serology/CSF diagnostics coordinated under one roof for unexplained young-onset dementia, stroke, meningitis, or psychiatric presentations. No referral required. Monday to Saturday.
040-44885000Emergency line: 040-46324365Clinical Forms of Neurosyphilis
Neurosyphilis presents as five clinically distinct forms — asymptomatic, meningeal, meningovascular, general paresis (parenchymatous), and tabes dorsalis — each with a characteristic timeline after primary syphilis, CSF profile, and outcome with IV penicillin treatment.
Asymptomatic neurosyphilis
Months to years after primary · CSF abnormalities onlyClinical features: None.
CSF: CSF abnormalities only — pleocytosis, raised protein, reactive VDRL.
Timeline: Months to years after primary infection.
Outcome with treatment: Excellent with treatment.
Meningeal neurosyphilis
Within 1–2 years of primary · headache, fever, neck stiffness, CN palsiesClinical features: Headache, fever, neck stiffness, CN palsies (especially CN VI, VII, VIII).
CSF: Lymphocytic pleocytosis, raised protein.
Timeline: Within 1–2 years of primary.
Outcome with treatment: Good with IV penicillin.
Meningovascular neurosyphilis
5–10 years after primary · stroke-like syndrome in a young personClinical features: Stroke-like syndrome in a young person; preceded by weeks of headache, behaviour change.
CSF: Meningitis pattern + ischaemia on MRI.
Timeline: 5–10 years after primary.
Outcome with treatment: Partial — residual stroke deficits possible.
General paresis (parenchymatous)
10–20 years after primary · progressive dementia, personality changeClinical features: Progressive dementia, personality change, psychiatric features, tremor, dysarthria, seizures.
CSF: Lymphocytosis, very high protein, reactive CSF VDRL.
Timeline: 10–20 years after primary.
Outcome with treatment: Arrests progression; limited reversal of established dementia.
Tabes dorsalis
10–30 years after primary · lancinating pains, AR pupils, sensory ataxiaClinical features: Lancinating pains, Argyll Robertson pupils, sensory ataxia, areflexia, Charcot joints.
CSF: Often minimal CSF changes; serology reactive.
Timeline: 10–30 years after primary.
Outcome with treatment: Arrests progression; pain treated separately.
Key Clinical Features of Neurosyphilis
The clinical signature of neurosyphilis spans the pathognomonic Argyll Robertson pupil, stroke in a young person from meningovascular syphilis, the dementia of general paresis, the spinal cord syndrome of tabes dorsalis, and the accelerated, atypical pattern seen in HIV co-infection — each of which is specifically assessed at KIMS.
The Argyll Robertson pupil — pathognomonic of late neurosyphilis
The Argyll Robertson (AR) pupil is small, irregular (often oval or asymmetric), reacts to near effort (accommodation) but NOT to light — the accommodation-light dissociation. It is caused by damage to the Edinger-Westphal nucleus and the pretectal nuclei in the midbrain. When found on examination, neurosyphilis is the leading diagnosis until excluded. The AR pupil does not occur in healthy ageing, glaucoma, or diabetes and should never be attributed to these conditions without syphilis serology.
Meningovascular syphilis — stroke in a young person
Meningovascular neurosyphilis produces stroke-like episodes from obliterative endarteritis — the blood vessels of the brain become inflamed and occluded. It typically occurs 5–10 years after primary syphilis. The presentation is a stroke in a young or middle-aged person (often 30–50 years), frequently preceded by weeks to months of headache, psychiatric change, or meningism. Any stroke in a person under 55 without the usual risk factors (hypertension, diabetes, smoking, atrial fibrillation) should have syphilis serology checked as part of the stroke workup at KIMS.
General paresis — the dementia of syphilis
GPI (general paresis of the insane) is treponema invasion of the brain parenchyma producing progressive dementia. Features: memory impairment, personality change, disinhibition, grandiosity (classically), and psychiatric symptoms. Accompanied by the AR pupil, tremor (particularly tongue tremor visible on protrusion), dysarthria, and hyperreflexia. It occurs 10–20 years after primary syphilis and is completely preventable by adequate treatment of primary or secondary syphilis.
Tabes dorsalis — spinal cord syphilis
Tabes dorsalis results from degeneration of the posterior columns and dorsal roots of the spinal cord, producing: lancinating (lightning) pains — sudden, severe, shooting pains in the limbs, abdomen, or face lasting seconds to minutes; sensory ataxia — wide-based gait worsening with eye closure (Romberg positive), from proprioceptive loss; areflexia (absent deep tendon reflexes); Argyll Robertson pupils; Charcot joints — painless joint destruction from loss of protective pain sensation. Lancinating pains respond partially to carbamazepine or gabapentin, but the nerve damage itself does not reverse with treatment.
HIV co-infection — accelerated and atypical neurosyphilis
HIV significantly increases the risk of neurosyphilis in syphilis-infected individuals, and changes its presentation: neurosyphilis can occur earlier (even in secondary syphilis), present atypically, and may not be reliably detected by standard serology (false-negative VDRL in high-titre HIV patients). Every HIV-positive patient with syphilis at KIMS receives CNS evaluation including LP, and lower thresholds are used for diagnosing and treating neurosyphilis. High-titre VDRL (≥1:32) in an HIV-positive person warrants LP regardless of neurological symptoms.
Diagnosis at KIMS
Diagnosis at KIMS — Serology, CSF Analysis, MRI, and Post-Treatment Monitoring
Neurosyphilis diagnosis at KIMS combines screening serology (VDRL/RPR) with confirmatory treponemal testing (TPHA/ FTA-ABS), CSF analysis with CSF VDRL and TPHA, MRI brain for damage and alternative diagnoses, and structured post-treatment CSF and serum monitoring at 6 months.
Serology — the essential first test
Screening: VDRL (Venereal Disease Research Laboratory) or RPR (Rapid Plasma Reagin) — non-treponemal tests that become reactive in active syphilis and decline with treatment (useful for monitoring). Confirmation: TPHA (Treponema pallidum Haemagglutination Assay) or FTA-ABS (Fluorescent Treponemal Antibody Absorption) — treponemal-specific tests that remain reactive lifelong after syphilis, regardless of treatment. A reactive TPHA in a patient with neurological symptoms and no previous documented syphilis treatment is sufficient indication to proceed to CSF analysis.
CSF analysis — for confirming neurosyphilis
LP for: cell count (lymphocytic pleocytosis ≥5 WBC/mm³ supports neurosyphilis); protein (elevated supports neurosyphilis); CSF VDRL (highly specific for neurosyphilis when reactive — a reactive CSF VDRL essentially confirms the diagnosis; negative CSF VDRL does not exclude it); CSF TPHA (sensitive but less specific than CSF VDRL for neurosyphilis). The combination of reactive serum TPHA + CSF pleocytosis + reactive CSF VDRL is diagnostic of neurosyphilis. Asymptomatic neurosyphilis: CSF abnormalities without symptoms — still requires IV penicillin treatment.
MRI brain — assessing damage and ruling out alternatives
MRI brain shows: cortical atrophy in GPI; ischaemic changes in meningovascular syphilis (small vessel lacunar infarcts or larger arterial territory infarcts); meningeal enhancement in meningeal neurosyphilis; gumma (rare — mass lesions from granulomatous inflammation, mimicking tumour). MRI also excludes alternative diagnoses.
Post-treatment monitoring
CSF is re-examined at 6 months after IV penicillin: cell count should normalise within 6 months; VDRL titre should decline 4-fold within 6–12 months. Serum VDRL/RPR is monitored at 6, 12, and 24 months. Failure of CSF pleocytosis to normalise at 6 months indicates treatment failure and requires retreatment. The TPHA/FTA-ABS in serum remains reactive lifelong — it cannot be used to monitor treatment success.
Treatment
Management at KIMS — IV Benzylpenicillin G, Penicillin Alternatives, Symptomatic Care, Jarisch-Herxheimer Watch, and Partner Notification
IV Benzylpenicillin G — The Gold Standard
KIMS neurosyphilis treatment protocol: IV benzylpenicillin G 18–24 million units per day, administered as 3–4 million units every 4 hours by continuous or intermittent IV infusion, for 10–14 days.This is the only treatment proven to achieve treponemicidal levels in the CSF. Oral penicillin does NOT achieve adequate CSF levels and is not acceptable for neurosyphilis.
After the IV course: IM benzathine penicillin G 2.4 million units once weekly for 3 doses (to ensure any residual peripheral infection is treated). All patients are counselled on partner notification and all current sexual partners are screened.
For Penicillin-Allergic Patients
Doxycycline 200mg twice daily for 28 days is the alternative for mild penicillin allergy (rash).
For true penicillin anaphylaxis, penicillin desensitisation followed by IV penicillin is the preferred approach — doxycycline has lower CSF penetration and limited evidence for neurosyphilis. This is arranged at KIMS in conjunction with the allergy/immunology team.
Symptomatic Management Across the Five Forms
• Lancinating pains (tabes dorsalis): Carbamazepine 200–400mg twice daily or gabapentin 300–900mg three times daily.
• Dementia (GPI): Cognitive support, occupational therapy, caregiver counselling. Treatment stops progression but rarely reverses established dementia.
• Seizures: Levetiracetam or valproate, managed per KIMS epilepsy protocols.
• Psychiatric features: Low-dose antipsychotics for agitation or psychosis while awaiting IV penicillin to take effect. Psychiatric symptoms often improve partially with IV penicillin.
The Jarisch-Herxheimer Reaction — Anticipate and Manage
Within 6–12 hours of the first penicillin dose, approximately 25–30% of patients develop fever, rigors, hypotension, and worsening neurological symptoms — the Jarisch-Herxheimer reaction (JHR), caused by the massive release of treponemal antigens from dying spirochaetes.
It is self-limiting, lasting 12–24 hours. At KIMS, patients are monitored for JHR and managed with paracetamol, IV fluids, and observation. JHR is more common and potentially more severe in early syphilis than in neurosyphilis, but should be anticipated.
Related Conditions
Neurosyphilis belongs to the family of infectious and post-infectious neurological disorders evaluated and managed at KIMS Neuroscience:
FAQs
Frequently Asked Questions
The Argyll Robertson pupil on examination. An unexplained stroke at 38. Dementia in a 42-year-old professional. Neurosyphilis is still here. Still mis-diagnosed. Still perfectly treatable with 14 days of IV penicillin.
At KIMS Neuroscience, Secunderabad, Hyderabad, syphilis serology is part of every unexplained neurological workup, CSF analysis is arranged when indicated, and IV penicillin is started promptly when neurosyphilis is confirmed. Call 040-44885000.
International enquiries: info@kimsneurosciences.com