Diagnosis Of Neurosyphilis Research Articles

Treponemal Tests for Neurosyphilis—Less Accurate Than What We Thought?

Treponema pallidum subsp. pallidum (hereafter termed T. pallidum) is the bacterium that causes syphilis. Neuroinvasion by T. pallidum occurs early in the course of disease (1-3) and can lead to asymptomatic meningitis that, untreated, can progress to symptomatic neurosyphilis. Early forms of symptomatic neurosyphilis include meningitis, hearing loss, vision loss, and stroke. Late forms include dementia (general paresis) and sensory ataxia (tabes dorsalis). Cerebrospinal fluid (CSF) analysis is crucial for diagnosis of asymptomatic and symptomatic neurosyphilis, but there is no perfect “gold standard” diagnostic test. Typical CSF abnormalities include mild mononuclear pleocytosis and elevated protein concentration. The CSF-Venereal Disease Research Laboratory (VDRL) test is specific but not sensitive, and particularly in early neurosyphilis, may be nonreactive. The “party line” has been that CSF treponemal antibody tests, while lacking the specificity of the CSF-VDRL, are diagnostically sensitive and can be used to rule out the diagnosis of neurosyphilis in equivocal cases. A systematic review by Harding and Ghanem (4) published in this issue of Sexually Transmitted Diseases challenges this tenet. In their review, the authors assessed studies that described the performance of CSF treponemal tests. They focused on the negative predictive value of these tests and restricted the analysis to studies in which controls were individuals who had syphilis but not neurosyphilis, an approach that is most relevant to clinical practice. Perhaps not surprisingly for a disease that lacks a gold standard diagnostic test, the authors found that the sensitivity of the CSF treponemal tests varied with how neurosyphilis was defined. If CSF-VDRL reactivity was used to establish the diagnosis, the sensitivity of the CSF treponemal antibody tests consistently approached 100%, but if broader criteria were used, particularly including clinical manifestations, the sensitivity was lower and more variable (22.2%-100%). Treponemal antibodies are directed against T. pallidum proteins, as detected by the fluorescent treponemal antibody absorbed (FTA-ABS) test, the T. pallidum particle agglutination (TPPA) test, the T. pallidum hemagglutination (TPHA) test or various enzyme immunassays (EIAs). Another treponemal test included in the analysis, the microhemagglutination-T. pallidum (MHA-TP), is no longer commercially available. The FTA-ABS, TPPA and TPHA tests measure IgG and IgM antibodies to native T. pallidum antigens, while the EIA assays detect IgG and IgM antibodies to recombinant treponemal proteins, usually TpN15, TpN17, and TpN47. For the FTA-ABS, TPPA and TPHA tests, the patient's serum or CSF is mixed with sorbent to remove cross-reactive antibodies to non-pathogenic treponemes. CSF samples that are nonreactive by FTA-ABS test are often reactive when the absorption step is omitted (5). Because EIA does not require the pre-absorption step, it could potentially be a more accurate test. However, there are no currently published studies using EIA on CSF to test this hypothesis. In the studies analyzed by Harding and Ghanem, it is difficult to determine whether the treponemal antibodies measured in the CSF were made intrathecally or in the periphery. Some investigators have argued that CSF:serum treponemal antibody ratios or indicies corrected for CSF and serum albumin or IgG concentrations can differentiate between intrathecal and peripheral antibody production and thus distinguish true CNS infection from passive diffusion of antibody from the peripheral blood (6-8). Sera from patients with reactive CSF FTA-ABS and CSF-TPPA tend to have higher treponemal antibody titers than sera from those with non-reactive tests, suggesting that a reactive CSF FTA-ABS or CSF-TPPA may simply be a surrogate for higher antibody concentration in sera (6, 9, 10). A study of the diagnostic utility of the CSF-TPHA suggested that a CSF titer >1:320 was as good as an elevated antibody index for neurosyphilis diagnosis (8), suggesting that there may be a CSF treponemal antibody concentration above which intrathecal antibody production is more likely. Distinguishing the source of CSF treponemal antibodies is important in assessing the accuracy of CSF treponemal tests. However, Harding and Ghanem did not include studies using such indices in their review. Syphilis and HIV co-infection occurs commonly worldwide (11, 12). Diagnosing neurosyphilis in HIV-infected patients continues to be a challenge because HIV infection itself can cause CSF pleocytosis and elevated protein concentration. Only four of the studies (1, 3, 7, 13) assessed by the authors included HIV-infected patients, and one of the four studies had very small patient numbers (7), making it difficult for the authors to assess the accuracy of CSF treponemal tests in this patient population. This article highlights the challenges clinicians caring for patients with syphilis continue to face – imperfect tests for neurosyphilis that are neither very sensitive nor specific. As the authors point out, while a positive CSF-VDRL “rules in” neurosyphilis, a negative CSF FTA-ABS does not necessarily “rule out” the diagnosis, especially when patients have neurological symptoms or signs. As the incidence of syphilis continues to increase, especially among HIV-infected patients, further work to develop better neurosyphilis diagnostic tests is sorely needed.

Neurosyphilis with optical involvement in an immunocompetent patient: a case report

BackgroundNeurosyphilis became a rare disease after the introduction of antibiotics. The resurgence of syphilis in association with human immunodeficiency virus infection in the past decades increased the incidence of this tertiary form of the disease. However, in immunocompetent patients neurosyphilis remains uncommon and accurate diagnosis is challenging as the clinical presentation is unspecific and the validity of supportive laboratory tests is unclear.Case reportWe describe the case of a 60-year-old man who presented with a 6-month clinical picture of depression-like symptoms and recent sudden unilateral blindness. Medical history uncovered a primary syphilitic event 20 years before. The investigation led to the diagnosis of neurosyphilis with optical involvement in a patient who did not present with any signs of secondary syphilis. Treatment with penicillin G and topical steroids resulted in significant clinical improvement and resolution of the visual loss.ConclusionIn the well-established natural history of syphilis, primary syphilis is almost always followed by manifestation of the secondary form, which in turn precedes a period of latency. This case emphasizes the need for a high index of suspicion of neurosyphilis in an immunocompetent patient with nonspecific neuropsychiatric manifestations and an atypical course of syphilis infection.

A case report and DSA findings of cerebral hemorrhage caused by syphilitic vasculitis

Syphilis is now rare and easily misdiagnosed because of the wide use of antibiotics in the clinical. We report a case of cerebral hemorrhage in a patient with hypertension who was first diagnosed as hypertensive cerebral hemorrhage. However, treponema pallidum particle agglutination and rapid plasma regain tests of cerebrospinal fluid revealed the existence of neurosyphilis. Interestingly, digital subtraction angiography (DSA) showed severe stenosis in both middle cerebral arteries and right anterior cerebral artery. The case reminded us to pay attention to syphilitic vasculitis in patients with cryptogenic stroke. DSA sometimes may play a critical role in differential diagnosis of neurosyphilis.

Late-stage neurosyphilis presenting with severe neuropsychiatric deficits: diagnosis, therapy, and course of three patients

Neurosyphilis is an infectious disease that has reappeared over the past two decades. It is caused by Treponema pallidum subspecies pallidum that can affect the central nervous system (CNS) during any stage of the disease. Besides early CNS involvement predominantly presenting with symptoms of meningitis, a parenchymal affection of the brain leading to severe neuropsychiatric symptoms particularly emerges at later stages, but is rarely seen nowadays due to early antibiotic treatment. Together with the clinical findings, a characteristic combination of serological and cerebrospinal fluid (CSF) abnormalities leads to the diagnosis of neurosyphilis and is required to assess its activity. However, particularly at later stages of disease and after antibiotic treatment, serological and CSF abnormalities may become ambiguous and, therefore, difficult to interpret. This can be accompanied by persisting or fluctuating neuropsychological deficits. To this day, no well-controlled clinical data exists concerning the treatment of late-stage neurosyphilis, neither on type, optimal dosage, duration, and long-term efficacy of antibiotic therapy. Therefore, treatment and follow-up of late-stage neurosyphilis are challenging tasks. Here, we present three cases of neurosyphilis with severe neuropsychiatric symptoms in non-immunocompromised patients and a review of the recent literature.

Laboratory diagnosis of Treponema pallidum infection in patients with early syphilis and neurosyphilis through a PCR-based test

Syphilis is a sexually transmitted disease caused by Treponema pallidum. The diagnosis is based mainly in clinical presentation and non-specific assays. PCR-based diagnosis has been suggested as an attractive alternative method. The aim of this study was the validation of a PCR-based test for the diagnosis of early syphilis (ES) and neurosyphilis (NS). Clinical samples of mucocutaneous lesions and cerebrospinal fluid (CSF) specimens from patients previously diagnosed for ES and NS respectively using an enlarged gold standard, were tested by PCR. The reaction was done using primers targeting the tpN47 gene. Twenty out of 21 mucocutaneous samples from patients diagnosed with ES were positive by PCR, with a clinical sensitivity of 95%. Four out of 8 CSF samples from patients previously diagnosed with NS were positive by PCR, with a clinical sensitivity of 50%. The clinical specificity for both ES and NS was 100%. The PCR sensitivity and specificity for mucocutaneous samples allowed us to implement this assay in our laboratory for routine diagnosis. Although the sensitivity of the PCR in CSF was low, it may be useful to support clinical diagnosis.

Diagnóstico de la infección por Treponema pallidum en pacientes con sífilis temprana y neurosífilis mediante reacción de la polimerasa en cadena

Syphilis is a sexually transmitted disease caused by Treponema pallidum. The diagnosis is based mainly in clinical presentation and non-specific assays. PCR-based diagnosis has been suggested as an attractive alternative method. The aim of this study was the validation of a PCR-based test for the diagnosis of early syphilis (ES) and neurosyphilis (NS). Clinical samples of mucocutaneous lesions and cerebrospinal fluid (CSF) specimens from patients previously diagnosed for ES and NS respectively using an enlarged gold standard, were tested by PCR. The reaction was done using primers targeting the tpN47 gene. Twenty out of 21 mucocutaneous samples from patients diagnosed with ES were positive by PCR, with a clinical sensitivity of 95%. Four out of 8 CSF samples from patients previously diagnosed with NS were positive by PCR, with a clinical sensitivity of 50%. The clinical specificity for both ES and NS was 100%. The PCR sensitivity and specificity for mucocutaneous samples allowed us to implement this assay in our laboratory for routine diagnosis. Although the sensitivity of the PCR in CSF was low, it may be useful to support clinical diagnosis.

The great pretender

In November, 2009, a 40-year-old man presented to us because of diffi culty in walking, facial asymmetry, and numbness in both legs. His symptoms had begun 6 weeks earlier with a sensation of pins and needles in both thighs spreading distally. At the same time he noticed a left facial droop, with involvement of the right side soon after. There was no change in bladder or bowel function. He had diabetes mellitus and was receiving insulin. He had no history of signifi cant exposure to toxins or alcohol misuse. There was no family history of neurological problems. He had recently been found HIV negative on testing after starting a new heterosexual relationship and reported no symptoms of sexually transmitted infections. Physical examination showed no rash or lymphadenopathy. His left conjunctiva was injected; both pupils reacted normally. On neuro logical examination he had bilateral lower motor neuron facial weakness and mild proximal leg weakness with 4– power in hip fl exion, 4+ at the knees, with full power elsewhere. Tone was normal but refl exes were globally absent with fl exor plantar responses. There was no muscle wasting or fasciculations. Loss of pain sensation was elicited in both legs in a high stocking distribution extending to the upper thigh. Position sense was intact. A clinical assessment of subacute sensorimotor polyneuropathy was made, and the diagnosis of GuillainBarre syndrome was considered. Although diabetes can present with chronic predominantly sensory peripheral neuropathy, cranial mononeuropathy, and radiculoplexus neuropathy, we thought the last less likely in view of the bilateral facial weakness and the absence of pain. Cerebrospinal fl uid (CSF) analysis showed a high protein concentration and lymphocyte count (fi gure). Because Guillain-Barre syndrome is rarely associated with CSF pleiocytosis in immunocompetent patients, we did a VDRL test on CSF; the result was positive, as was that for serum (titre 1 to 128), confi rming an unexpected diagnosis of neuro syphilis. Our patient was treated with intravenous benzyl penicillin 5 mU every 6 h. After 14 days of treatment his sensory symptoms had resolved, and within a month after discharge he had regained full power, including of the facial muscles. At fi nal follow-up in November, 2010, a repeat HIV ELISA was negative and he had made a full recovery. He had disclosed the diagnosis to his sexual partner who underwent screening and treatment. Neurosyphilis can be divided into early and late forms. In our patient, a cellular response in the CSF, rapid symptom onset, and strongly positive serum VDRL favoured early disease with meningeal involvement. Late neurosyphilis manifests as tabes dorsalis and syphilitic paresis resulting from brain and cord parenchymal infection. There is evidence that the clinical spectrum of neurosyphilis has changed in the post-antibiotic era, with early forms now predominating. Diagnosis of neuro syphilis can be challenging and requires a combination of tests. Although CSF-FTA assays are reactive in more cases than the CSF-VRDL in all stages of syphilis, their specifi cities are less well established and they are not regarded as a valid basis for the diagnosis of neurosyphilis in isolation. By contrast, VDRL is highly specifi c in the CSF and is regarded as the standard serological test, but it reportedly has lower sensitivity. Immunocompetent patients with positive serum treponemal tests and compatible clinical signs should be treated for neurosyphilis if the CSF shows a raised protein concentration or leucocyte count. Syphilis is a great mimicker in clinical medicine, and neurosyphilis can occur early after infection, in many cases without accompanying peripheral manifestations. The diagnosis should be considered in patients presenting with symptoms and signs resembling Guillain-Barre syndrome and CSF pleiocytosis.

Étiologies des perforations de la cloison nasale observées dans un service de médecine interne

The purpose of this study was to describe and evaluate neuroimaging findings of patients with neurosyphilis.The neuroimaging studies of 14 patients with documented neurosyphilis were reviewed. Diagnosis was established in 14 patients with cerebrospinal fluid for a Treponema Pallidum Particle Agglutination (TPPA) test. All patients had reactive TPPA and Unheated Serum Regain test (USR) in their sera. Imaging studies included plain, contrast-enhanced CT of the brain, plain and gadolinium-enhanced MR, and MR angiography.In the 14 HIV-negative patients with neurosyphilis, CT and MR showed the presence of cerebral infarction in six cases, arteritis in four cases, nonspecific white matter lesion in three cases, acute syphilitic meningitis in one case and normal neuroimaging finding in one case. In addition, 4 in 14 patients had general paresis, and MRI showed high signal intensity on T2 -weighted images involving frontotemporal lobes, hippocampus and periventricular area. Treatment with penicillin significantly diminished the size of these high signal intensity on T2-weighted images with general paresis.These results suggest that MR and CT images have some characteristic manifestations in patients of neurosyphilis. Because early diagnosis and treatment of neurosyphilis are crucial to avoid persistent brain damage, the neuroimaging findings are valuable adjunct to clinical diagnosis and to provide useful information to follow-up after therapy.

Failure of knee osteotomy in a case of neuropathic arthropathy of the knee

Neuropathic arthropathy (Charcot’s joint) is a degenerative process that affects peripheral or vertebral joints as a consequence of a disturbance in proprioception and pain perception. The knee is one of the most frequently affected joints, but even when the diagnosis is made at an early stage there is no consensus on the best treatment options. An early diagnosis of neurosyphilis was made in a 55-year-old woman presenting a delayed union of an asymptomatic Schatzker type IV fracture of the proximal tibia. A medial opening wedge tibial osteotomy was performed to achieve fracture healing, to correct the medial depression of the articular surface, and possibly to avoid an early arthritis typical of the disease. To our knowledge, a knee osteotomy has never been reported at an early stage of neuropathic arthropathy. Even though the clinical and radiographic evaluation performed at 4 months follow-up showed a good stage of healing of the osteotomy and no typical features of neuropathic joint degeneration, at 8 months follow-up the knee was markedly deranged.

Neurosyphilis presenting with psychotic symptoms and status epilepticus

The widespread use of antibiotics in recent years has considerably modified the clinical features of neurosyphilis. Presently, atypical or masked forms of this disease often occur and obscure diagnosis, despite a thorough history and clinical work-up. Here, we report a patient with neurosyphilis presenting with psychotic symptoms who then developed status epilepticus and left limb weakness. Diffusion-weighted magnetic resonance imaging showed hyperintensity involving the right parietal, occipital and temporal lobes and the thalamus. Subsequent serological and cerebrospinal fluid tests confirmed the diagnosis of neurosyphilis. The coexistence of meningovascular syphilis, syphilitic meningitis, and general paresis resulted in the complex manifestation of this patients' condition, as described here in terms of the unusual presentation, evolution, and final diagnosis.

The Usefulness of Toluidine Red Unheated Serum Test in the Diagnosis of HIV-Negative Neurosyphilis

We retrospectively analyzed the Venereal Disease Research Laboratory test, Treponema pallidum particle agglutination test, and toluidine red unheated serum test (TRUST) in 41 cases of HIV-negative neurosyphilis and 34 non-neurologic syphilitic patient and found that serum-TRUST titers could be the indication of lumbar puncture in syphilitic patients and a reactive cerebrospinal fluid-TRUST is considered diagnostic to neurosyphilis.

Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis

The potential mechanisms for altered matrix metalloproteinase (MMP) or tissue inhibitors of matrix metalloproteinase (TIMP) function in patients with syphilis and HIV-1 co-infection (HIV-S) was unclear. To determine the expression of MMP-2, 9 and TIMP-1, 2, 4 in the serum and cerebrospinal fluid (CSF) of HIV-S patients, a total of 20 HIV-S patients and 8 controls were enrolled in a HIV-1 clinical cohort for diagnosis of neurosyphilis in Taiwan.Serum and CSF concentrations of MMP-2, 9, and TIMP-1, 2, 4 were determined by ELISA. Gelatin zymography was used to detect the expression of MMP-2 and MMP-9 in the CSF. Neurosyphilis was defined as a CSF white blood cell count ⩾20 cells/μL or a reactive CSF Venereal Disease Research Laboratory (VDRL). All the patients with HIV-S were males. Most (85%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ⩾1:32. The median age was 35years (IQR 30–43). The median CD4 T cell counts at the time of the diagnosis of syphilis were 270cells/μL (IQR 96–484). Ten patients (50%) had neurosyphilis based on a reactive CSF VDRL test (n=8) or increased CSF white cell counts ⩾20/μL (n=2). The concentrations of CSF MMP-9, TIMP-1, and TIMP-2 were significantly higher in patients with HIV-S than the controls (P<0.05). The CSF TIMP-4 concentrations were significantly lower in those with HIV-S (452pg/ml) than controls (3101pg/ml), P<0001. There were no significant differences in serum concentrations between the groups. The only finding that distinguished HIV-1 patients with from those without neurosyphilis is a significant higher expression of CSF MMP-9. In conclusion, the MMP/TIMP system was found to be dysregulated in patients with HIV-S regardless of whether they met the laboratory definition of neurosyphilis. The CSF level of MMP-9 was the only measure that distinguished those with or without neurosyphilis.

Comparisons of several laboratory tests in the diagnosis of neurosyphilis

Objective To compare the sensitivity and specificity of venereal disease research laboratory （VDRL） test versus several other laboratory tests in the diagnosis of neurosyphilis. Methods Lumber puncture was conducted to obtain cerebrospinal fluid （CSF） from untreated outpatients with latent syphilis （LS） or serofast outpatients with LS. Then, VDRL test, rapid plasma regain （RPR） test, Treponema pallidum particle agglutination （TPPA） assay, fluorescent treponemal antibody-absorption （FTA-ABS） test and protein quantification were performed on these CSF samples. The sensitivity, specificity, positive predictive value and negative predictive value were compared between VDRL test and four other laboratory tests in the diagnosis of neurosyphilis. Results Totally, 61 cases of latent syphilis were included in this study. The sensitivity, specificity,positive predictive value and negative predictive value were 93.44% （57/61）, 99.32%（293/295）, 96.61%（57/59）, 98.65% （293/297）for CSF-RPR, respectively, 91.80% （56/61）, 82.71% （244/295）, 52.34% （56/107）,97.99 （244/249） for CSF-TPPA, respectively, 93.44% （57/61）, 82.71% （244/295）, 52.78%（57/108）, 98.39%（244/248） for CSF-FTA-ABS, respectively, and 49.18%（30/61）, 97.29% （287/295）, 78.95% （30/38）,90.25% （287/318） for CSF protein quantification, respectively. Conclusions CSF-VDRL cannot be replaced by CSF-RPR, -TPPA, -FTA-ABS, or CSF protein quantification in the diagnosis of neurosyphilis. CSF-RPR shows a high sensitivity and specificity in the diagnosis of neurosyphilis, with an increased diagnostic capability （area under the receiver operating characteristic curve） compared with CSF-TPPA, CSF-FTA-ABS or CSF protein quantification. Key words: Neurosyphilis; Syphilis serodiagnosis; Sensitivity and specificity; Area under curve

The Changing Face of Neurosyphilis

The incidence of syphilis has increased over the past decade, particularly among HIV-positive patients, and the presenting clinical features have changed since the beginning of the HIV epidemic. The clinical manifestations of neurosyphilis are protean, and include acute stroke. In patients with HIV, the diagnosis and treatment of neurosyphilis is challenging. We review the clinical presentation, pathophysiology, and treatment of neurosyphilis, with emphasis on neurosyphilis in the HIV population, and neurosyphilis as a cause of acute stroke.

Symptomatic and asymptomatic early neurosyphilis in HIV-infected men who have sex with men: a retrospective case series from 2000 to 2007

The rise in serious complications of early syphilis, including neurosyphilis, particularly in those with HIV infection and in men who have sex with men (MSM), is of concern. To review the manifestations and management of neurosyphilis in a population of HIV-infected MSM. Retrospective review of patients with HIV and early neurosyphilis in three centres in Melbourne, Australia, in 2000-07. Eighteen male HIV patients met the criteria for diagnosis of early neurosyphilis. Thirteen patients (72.2%) had neurological symptoms: six with headache (33.3%), four with tinnitus (22.2%) and five with impaired vision (27.8%), and one patient each with ataxia, leg weakness and anal discharge with faecal incontinence. Five patients (27.8%) reported no neurological symptoms. All had serum rapid plasma reagin (RPR) titres ≥1:32 and all except one had cerebrospinal fluid positive for syphilis fluorescent treponemal antibodies-absorbed. After treatment with 14-15 days of 1.8 g intravenous benzylpenicillin 4-hourly, 12 of 17 patients (71%) demonstrated a four-fold drop in serum RPR titre over 6-12 months and were considered successfully treated. A rise in RPR was noted in three patients during the 12-month follow-up period, suggesting re-infection or recurrence. HIV-infected patients found to have syphilis either because of symptoms or by routine screening should be carefully assessed for neurological, ophthalmic and otological symptoms and signs. A low threshold for a diagnostic lumbar puncture to exclude the diagnosis of neurosyphilis enables appropriate administration and dose of penicillin for treatment, which appears successful in ~75% of cases.

Deterioration of MRI findings related to Jarisch–Herxheimer reaction in a patient with neurosyphilis

Syphilis is a systemic infection that can involve the central nervous system at any stage. In patients with syphilis, Jarisch–Herxheimer reaction (JHR) usually occurs within 24 h after antibiotic treatment [5]. Although status epilepticus (SE) due to JHR has been reported in some patients with neurosyphilis [2, 3], neuroradiological findings related to JHR have not been well described. Here we report the case of a patient with parenchymatous neurosyphilis who developed SE due to JHR, which was accompanied by deterioration of MRI findings in the acute phase of the reaction. A 48-year-old man presented with simple partial seizures 4 months before admission to our hospital. The seizures were well controlled by carbamazepine in the local hospital. He was admitted to our hospital with gradually worsening unsteady gait for a 2 weeks duration. On neurologic examination, homonymous hemianopia of the left lower quadrant, anisocoria, and truncal ataxia were observed. Neuropsychological examination showed impaired memory and attention; he was HIV negative. Cerebrospinal fluid (CSF) examination showed a mononuclear WBC count of 26/mm with elevated total protein levels (70 mg/dL). There were no atypical cells in CSF. Rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS) titers in the serum and the CSF were positive (serum RPR 1:16, serum FTA-ABS 1:1,280, CSF RPR 1:8, CSF FTA-ABS 1:1,024). MRI of the brain showed hyperintense lesions on T2-weighted images in the frontal, temporal, and occipitoparietal lobes; corpus callosum; and cingulate gyrus (Fig. 1a). The cerebral cortices in these lesions were partially enhanced on contrast-enhanced T1-weighted images (Fig. 1d, g). Consequently, a diagnosis of parenchymatous neurosyphilis was made, and the patient was started on a treatment with intravenous penicillin G at a dose of 24 million units daily for 2 weeks. However, the patient developed chills and fever 7 h after initiation of treatment, and these constitutional symptoms were followed by nuchal rigidity and fluctuations of consciousness. Subsequently, 16 h after treatment, the patient developed continuous seizures of the right upper extremity with severely impaired consciousness. The condition was diagnosed as developing complex partial SE. Repeat MRI study showed that pre-existing hyperintense lesions on T2-weighted images were enlarged in the frontal lobes (Fig. 1b). Furthermore, intense cortical enhancement in the frontal lobes, left occipitoparietal lobe, cingulate gyrus, and insula was demonstrated (Fig. 1e, h). Intravenous methylprednisolone (250 mg/day for a day) was administered on the day following commencement of the new set of symptoms. The seizures were well controlled with carbamazepine. Although visual field deficits persisted, unstable gait and cognitive dysfunction were significantly improved. Contrast enhancement in the cerebral cortices J. Kobayashi (&) Y. Nakagawa S. Tobisawa E. Isozaki R. Koide Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan e-mail: j3737@tmnh.fuchu.tokyo.jp

Ocular Perineuritis Secondary to Neurosyphilis

Syphilis is a condition caused by the spirochete Treponema pallidum (T. pallidum). Because of its ubiquitous nature, it has been coined as "the great masquerader." Syphilis can present with a wide array of clinical symptoms and manifestations, making it difficult to diagnose. The spectrum of visual system manifestations is broad and involves the anterior and posterior segments. We report a rare case of ocular perineuritis in an HIV-positive patient with neurosyphilis. A 33-year-old HIV-positive white male presented with blurred vision and floaters of 2 weeks duration. He reported coinciding neurological symptoms including headaches, nausea, and extreme weight loss. He also manifested an erythematous rash on his scalp. Fundoscopy revealed bilateral disc edema. Syphilitic ocular perineuritis is a condition that manifests with swollen optic discs in the absence of raised intracranial pressure or visual disturbance. This condition is due to inflammation of the optic nerve sheath and is often mistaken for papilledema or papillitis. Optic perineuritis is an infrequently reported complication of syphilitic disease. Early diagnosis of neurosyphilis and its complications is critical, because it is easily treated with penicillin when initiated early on.

REVIEW: Neurosyphilis: A Historical Perspective and Review

Treponema pallidum subspecies pallidum, the causative agent of syphilis, disseminates to the central nervous system within days after exposure. Clinical manifestations can occur during any stage of the infection, and include asymptomatic neurosyphilis, acute meningeal syphilis, meningovascular syphilis, paretic neurosyphilis, and tabetic neurosyphilis. The majority of cases are reported in HIV-infected patients but the epidemiology of modern neurosyphilis is not well defined because of the paucity of population-based data. Decreasing reports of late neurosyphilis have been countered with increasing reports of early neurologic involvement. This review summarizes the clinical manifestations, diagnosis, and therapy of neurosyphilis, focusing on areas of continued controversy, and highlighting several important questions that remain unanswered. Since 2000, the rates of syphilis continue to increase. Given the effectiveness of penicillin therapy, these trends suggest a failure of prevention. Regrettably, rather than become an infection of historical significance, syphilis in the era of HIV continues to challenge researchers and clinicians.

CXCL13 as a Cerebrospinal Fluid Marker for Neurosyphilis in HIV-Infected Patients With Syphilis

Asymptomatic neurosyphilis is more difficult to diagnose in human immunodeficiency virus (HIV)-infected patients because HIV itself can cause cerebrospinal fluid (CSF) pleocytosis. The proportion of CSF lymphocytes that are B cells is elevated in neurosyphilis, suggesting that the CSF concentration of the B cell chemoattractant, chemokine (C-X-C motif) ligand 13 (CXCL13) concentration may also be elevated. CSF and blood were collected from 199 HIV-infected patients with syphilis and neurosyphilis. Serum and CSF CXCL13 concentrations were determined. Patients with neurosyphilis had higher CSF and serum CXCL13 concentrations compared to patients with syphilis but not neurosyphilis. The odds of having symptomatic neurosyphilis were increased by 2.23-fold for every log increase in CSF CXCL13 concentration and were independent of CSF white blood cell and plasma HIV RNA concentrations, peripheral blood CD4+ T cell count and use of antiretroviral medications. A cut-off of 10 pg/mL CSF CXCL13 had high sensitivity and a cut-off of 250 pg/mL or evidence of intrathecal synthesis of CXCL13 had high specificity for diagnosis of both symptomatic and asymptomatic neurosyphilis. CSF concentrations of CXCL13 declined after treatment for neurosyphilis. CSF CXCL13 concentration may be particularly useful for diagnosis of neurosyphilis in HIV-infected patients because it is independent of CSF pleocytosis and markers of HIV disease.

Meningovascular neurosyphilis: a report of stroke in a young adult

A young adult patient with meningovascular neurosyphilis in the form of acute ischemic stroke with right hemiparesis and speech disturbance is reported. CT scan showed features of ischemic infarct and extensive laboratory studies were made before the diagnosis ultimately was revealed. Such cases could result in confusion for the clinician, and high index of clinical suspicion of this condition is required since syphilis is not routinely tested, as routine screening is seen to be of low diagnostic yield. As clinical practice indicates, it remains a difficult problem approaching diagnosis of neurosyphilis, and this is achieved through exclusion of neurosyphilis as a clinical possibility.