Certain physical signs and symptoms in neurosyphilis may cause suspicion of a somatoform disorder; they include lancinating pain, transient hemiparesis, transient sensory deficit, paresthesias, headache, ataxia, dysphasias, and multiple sclerosis-like symptoms. The paretic patient may exhibit histrionic behavior with grandiosity, raising suspicion of a primary conversion disorder rather than a neuro-organic etiology. To summarize, the typical neuropsychiatric presentations of neurosyphilis include delirium, mania, hallucinosis or psychosis, dementia, and depression. Std Screening nearest North Carolina. Coexistent meningovascular syphilis, syphilitic meningitis, and general paresis has been reported. It presents with complex evolving manifestations. 31
Ocular syphilis is a new epidemic. Ocular involvement 32 often includes anterior uveitis or panuveitis (granulomatous or nongranulomatous), retinitis, retinal vasculitis, vitreitis, and papillitis. 33 , 34 Symptoms of photophobia and dimming of vision obviously could develop. All symptoms can resolve with typical treatment of neurosyphilis, namely, intramuscular procaine penicillin-G. This is a relatively common manifestation of late syphilis. Adhesions of the iris to the anterior lens (synechiae) may be present, which may produce a fixed pupil; this should not be confused with Argyll Robertson pupil. Bilateral tonic pupils have been noted, with light-near dissociation and denervation hypersensitivity. A particular condition—acute syphilitic posterior placoid chorioretinitis (ASPPC)—distinct from ocular syphilis has been reported. 35 Angiographically, there is hyperfluorescence in the area of the perineuritic lesion, often with scattered focal hypofluorescence(leopardspotting). 36
Syphilis and HIV are frequently found in the same patient, given the epidemiologic risk factors. Thus, each should be tested for after receiving consent. CSF abnormalities in patients with the concomitant infections include a higher protein content and more impressive pleocytosis. Std screening closest to North Carolina. Additionally, the response to treatment is less pronounced. Therapeutically, some authors purport that highly active antiretroviral therapy to reverse immunosuppression from HIV may help mitigate neurologic complications of syphilis. North Carolina std screening. 14 , 37 , 38 , 39 , 40 , 41 , 42 , 43
CSF abnormalities include elevated protein levels and pleocytosis, which are found in up to 70% of patients. In addition, the CSF VDRL result is reactive. CSF examination is recommended in all patients with untreated syphilis of unknown duration or of duration greater than 1 year. Because standard PCN-G benzathine therapy for early syphilis does not achieve treponemicidal levels in the CSF, some experts advise lumbar puncture in persons with secondary and early latent syphilis, with follow-up examinations for patients with abnormalities.
Perform lumbar puncture in the evaluation of latent syphilis of more than 1-year duration, in suspected neurosyphilis, and in late complications other than symptomatic neurosyphilis because asymptomatic neurosyphilis may coexist with other late complications. A serum RPR titer of 1:32 seems to be the best cutoff point to decide whether or not to perform a lumbar puncture. 46 Abnormal CSF findings can then be serially monitored as a guide to therapy. Overall, CSF pleocytosis continues to define disease activity. Documentation of resolution of CSF findings following therapy is required to confirm curative treatment.
Syphilitic infection produces 2 types of antibodies, the nonspecific reaginic (immunoglobulin E-mediated) antibody (ie, anticardiolipin) and specific antitreponemal antibody, which are measured by the nontreponemal and treponemal tests, respectively. Of note, cardiolipin is a substance extracted from heart tissue that is used as the antigen in flocculation and precipitation tests for syphilis. Test results can be reactive in persons with any treponemal infection, including yaws, pinta, and endemic syphilis (ie, bejel, which is due to another strain). The VDRL test and the rapid plasma reagin (RPR) test are nontreponemal tests, whereas FTA-ABS and microhemagglutination assay-T pallidum (MHA-TP) are treponemal tests.
The RPR test is preferred over the VDRL test in an office setting. The 2 tests are equally sensitive. They may be used for initial screening and for serial follow-up. In tertiary syphilis, the VDRL test remains, for the most part, positive indefinitely. Response to treatment can be assessed quantitatively by evaluating the antibody titers of dilution. For example, the VDRL titers usually reach 1:32 or higher in secondary syphilis; a persistent fall in titer following treatment of early syphilis provides essential evidence of an adequate response to therapy. A rising titer may indicate reinfection or inadequate treatment. VDRL titers do not correspond directly to RPR titers, and sequential quantitative testing must consistently use the same test.
The cardiolipin antigen used in the nontreponemal tests is found in other tissues, resulting in false-positive serologic test results. These false-positive results can be found in persons with nonvenereal treponemal infections (eg, yaws, pinta, bejel), those who have received certain immunizations (eg, smallpox), pregnant women, patients with acute or chronic infections (eg, infectious mononucleosis, malaria), or those with certain chronic conditions (eg, aging, intravenous drug usage, autoimmune disorders, malignancy). False-positive RPR test results are identified by excluding syphilis with a nonreactive treponemal test. Std screening near me North Carolina. Biological false-positive CSF reagin test results may result from tuberculosis or pyogenic or aseptic meningitis. However, even with sufficient treatment, patients sometimes have a persistent low-level positive nontreponemal test, which is referred to as a serofast reaction.
More sensitive and specific markers for neurosyphilis have been investigated. These include oligoclonal bands and certain intrathecally produced antitreponemal immunoglobulin M and immunoglobulin G antibodies. Polymerase chain reaction for detection of treponemal nucleic acids in the CSF has been suggested to also be useful and confirmatory. 52 A new, experimental diagnostic approach involves relying on a CSF marker—known as a B-cell chemotactant—termed chemokine CXC motif ligand 13. Laboratory verification of CNS involvement in syphilis remains a challenge. Detection of anticardiolipin and antitreponemal antibodies in CSF in patients with neurosyphilis is problematic. A new commercially available test, the INNO-LIA Syphilis Score molecular test may serve as a new generation of valid tests to identify patients with silent neurosyphilis as well as patients with active intrathecal synthesis of IgG antibodies. 53 Generally, these have not reached a clinical level of usebecause theirroleremains unclear.
Some investigators have recommended that patients who are infected with HIV have a lumbar puncture to evaluate their response to treatment and that the lumbar puncture be performed at least 6 months after treatment, along with a clinical evaluation and periodic serologic testing for at least 3 years, if not for life, depending on the underlying process. Std Screening Near Me North Dakota. Std screening nearest North Carolina. CSF VDRL results may take years to revert to normal after successful treatment; therefore, normalization of CSF pleocytosis must be checked to monitor the response to therapy.
Patients with general paresis (parenchymatous neurosyphilis) have demonstrated frontocortical atrophy and disseminated frontal high-signal lesions. These patients have also been found to have cerebral atrophy (cortical thinning of the temporal and frontoparietal regions bilaterally, most prominent in the temporal regions); mesiotemporal (amygdalar) T2 hyperintensity; ventriculomegaly; and pathological T2 hypointensity of the globus pallidus, putamen, head of the caudate, and thalamus. In those with general paresis, MRI may be of prognostic value. 56 The iron (ie, ferritin) deposition and increased frontal atrophy correlate with the progression of neuropsychiatric disturbances, apparently independent of CSF changes.
Also reported is newly diffuse white-matter T2 hyperintensity, which was seen to be partially reversible after therapy and thus thought to be due to edema and gliosis. 57 It was not specific for neurosyphilis in that it has also been seen with Binswanger disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, progressive multifocal leukoencephalopathy, HIV encephalitides, and subacute sclerosing panencephalitis. Std screening near me North Carolina. Diffusion-weighted imaging (DWI) on MRI serves well to demonstrate cerebral syphilitic gumma, revealing findings that include juxtacortical lesional nodular enhancement, moderately restricted diffusion, and dural tail and surrounding vasogenic edema. 58 , 59
Single-photon emission computed tomography (SPECT) is a useful method for evaluating an inflammatory state and for assessing the effect of therapy on neurosyphilis. Increased cerebral blood flow is detectable by iodine-123 (123 I) N -isopropyl-p -iodoamphetamine SPECT, consistent with the active inflammatory state of neurosyphilis; its disappearance correlates with successful treatment with penicillin. North Carolina std screening. SPECT can be diagnostically sensitive in the setting of otherwise unremarkable MRI findings. 64 , 65
Reports of electrophysiologic features in tabes dorsalis indicate absent H reflexes and impeded tibial nerve sensory evoked potentials (with absent cortical potentials) consistent with pathologic involvement of the dorsal roots and the dorsal funiculi (stemming from secondary wallerian degeneration). Some investigators contend that posterior tibial somatosensory evoked potentials are a sensitive marker for detecting subclinical root damage in meningeal syphilis and may aid in evaluating the extent to which neurosyphilitic spinal root damage has developed. Normal findings on nerve conduction studies are usually expected because motor fibers are rarely involved; partial anterior horn cell dysfunction is known to occur. 67
A cure for neurosyphilis does not exist in patients infected with HIV. After treatment for syphilis, PCN fails to produce a biologic cure and relapse is prevented by the immunologic status of the host. In a way, neurosyphilis is considered an opportunistic infection. Prolonged survival despite depleted helper T cells is associated with a recrudescence of syphilis. The course of neurosyphilis is believed by some investigators to be more rapid in patients co-infected with HIV, consistent with a potentiating effect. Others maintain that the course is no more aggressive in HIV-positive patients, nor is it atypical or more refractory to treatment.
Corticosteroids (along with intravenous PCN) have been used in the clinical setting of cerebral gummata. 87 Massive doses (ie, dexamethasone at 12 mg/d intramuscularly for 1 mo, followed by methylprednisolone at 16 mg/d) have been prescribed. On occasion, neurosurgical decompression of coexistent hydrocephalus may be indicated. With treatment, the space-occupying lesions undergo complete resolution on neuroimaging studies and the clinical picture improves. If seizures are present, treat accordingly.
Syphilitic optic neuropathy (SON) (including iridocyclitis and posterior placoid chorioretinitis) has been recently reported to present as the sole and initial clinical manifestation of HIV and syphilis co-infection. 88 , 89 This should be considered upon presentation of bilateral uveitis of uncertain origin, especially if the patient has a rash and/or headache. Adjunctive steroid therapy is touted to be advantageous toward improvement in optic nerve functional outcomes with SON. More rigorous studies are required for validation of this pharmacologic approach. 90 Ocular symptoms in HIV+ patients should be treated as neurosyphilis whereas ocular symptoms in non-HIV+ patients can be treated as secondary syphilis. 91
Patients should be informed about the possibility of experiencing the adverse Jarisch-Herxheimer reaction. This is the transient febrile reaction after any therapy for syphilis. It occurs within the first few hours and peaks at 6-8 hours. The Jarisch-Herxheimer reaction follows a self-limited course; sedation (eg, with diazepam or haloperidol ) and general supportive measures are indicated. Admit the patient to the hospital if neurologic involvement is noted. Otherwise, treat with steroids and antipyretics, as indicated. 93
The pathogenesis of the Jarisch-Herxheimer reaction is unclear. Liberation of antigens from the spirochetes and/or activation of the complement cascade or obscure endotoxemia may be the cause. The theory of local Jarisch-Herxheimer reactions precipitating serious damage is undersupported; however, some experts report resultant coronary ostial occlusion or even rupture of an aortic aneurysm consequent to antibiotic therapy. In addition, the reaction might induce early-onset labor or cause fetal distress in pregnant women, but these possibilities should not prevent or delay treatment. 94
Prevention of this rare and alarming reaction involves aspiration into the syringe following insertion of the needle prior to intramuscular injection. Should any blood be present, the needle should be re-placed in a different site. In that the onset of symptoms is early, exclude anaphylaxis. If the patient is experiencing anaphylaxis, administer epinephrine and antihistamines. Advise the patient to calm down, and offer verbal reassurance. Restrain the patient if necessary. Prescribe diazepam at 10 mg per rectum, intramuscularly, or intravenously as needed for convulsions and/or overarousal.
Bactericidal concentrations are approximately 30 IU/L or 0.02 mg/L. Intravenous aqueous PCN, at a dose of 0.15 million IU/kg body weight per day, in divided doses, produces such concentrations. According to World Health Organization recommendations, the minimal treponemicidal CSF benzyl PCN serum concentration is greater than 0.018 mg/L. The maximum concentration, which is far higher, as set by the Clinical Effectiveness Group of the Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases, is 0.36 mg/L. This higher dose might be preferable because it results in more rapid elimination of treponemes. Intervals during which antibiotic levels are less than fully treponemicidal should not exceed 24-30 hours.
Treatment failures are reported; concomitant HIV infection may increase the failure rate. Benzathine PCN does not provide measurable levels of PCN in the CSF; therefore, examining the CSF in all patients with latent syphilis is advisable to exclude asymptomatic neurosyphilis, especially in patients who are HIV positive. The Centers for Disease Control and Prevention recommends re-treatment if clinical signs or symptoms of syphilis persist or recur, the titer of a nontreponemal test shows a sustained fourfold increase, or an initially high-titer nontreponemal test fails to show a fourfold decrease within a year.
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Other antibiotics, as alternative regimens, have not been studied sufficiently, and their routine use is not recommended. If patients are allergic to PCN, either tetracycline or doxycycline probably is effective. Std Screening Near Me New York. Pregnant women should not receive doxycycline. Typically, tetracycline hydrochloride at 500 mg orally 4 times per day or doxycycline at 100 mg orally twice daily for 4 weeks is prescribed. Defining the efficacy of azithromycin for early syphilis may simplify therapy. Incidentally, the emergence of azithromycin-resistant T pallidum has been reported.
Photosensitivity and/or hepatic dysfunction may be issues. Given the longer treatment schedule, encourage compliance and ensure follow-up. Desensitization (using escalating doses of phenoxymethylpenicillin see penicillin V ) to PCN may be a better alternative; this should be undertaken after skin testing confirms the allergic state. Std Screening in North Carolina. Parenteral ceftriaxone is reportedly successful for the treatment of symptomatic neurosyphilis in patients allergic to PCN; proven good CNS penetration and unusually long serum half-life (approximately 7 h) make it advantageous; CSF levels should be measured.