Use of cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis: a three-case report

Introduction: Previous retrospective studies have demonstrated that the concentration of chemokine ligand CXCL13 in cerebrospinal fluid (CSF-CXCL13) is a promising biomarker in the diagnosis of neurosyphilis and, additionally, in the monitoring of therapeutic efficacy. Objective: To describe three cases of patients with neurosyphilis (NS) treated at Hospital Universitário Gaffrée e Guinle, in Rio de Janeiro, Brazil, with suspected active syphilis with neurological symptoms. Case report: Three patients from Rio de Janeiro, Brazil, were investigated for symptomatic NS. The concentration of CSF-CXCL13 was prospectively performed by enzyme-linked immunosorbent assay (ELISA) in all participants at baseline and in follow-up visits at 3 months after therapy. CSF-CXCL13 concentrations were significantly higher in all three patients with established NS. The CSF-CXCL13 concentrations decreased after 3 months of therapy compared to baseline in all cases reported. The added high concentration of CSF-CXCL13 plus CSF-TPHA reactivity above 1:40 titer agreed with the diagnosis of NS in 100% of the cases. Conclusion: In this case series, we present three cases of NS diagnosed using CXCL13 in CSF as a complementary test. These case series suggest that the clinical use of CSF-CXCL13 is useful as a supplementary biomarker for NS and for monitoring the effectiveness of NS therapy, especially in patients with nonreactive CSF-VDRL, excluding other neurologic diseases

A comparison of nontreponemal tests in cerebrospinal fluid for neurosyphilis diagnosis: equivalent detection of specific antibodies / Uma comparação de testes não treponêmicos no líquido cefalorraquidiano para diagnóstico de neurossífilis: detecção equivalente de anticorpos específicos

ABSTRACT Syphilis is a re-emerging sexually-transmitted infection, caused by the spirochete Treponema pallidum, that may penetrate early into the central nervous system. The venereal disease research laboratory test (VDRL) on the cerebrospinal fluid (CSF) is the most widely used for neurosyphilis diagnosis. We evaluated the performance of two other nontreponemal tests (rapid plasma reagin [RPR] and unheated serum reagin [USR] tests) in comparison with the VDRL in CSF. Methods: We analyzed CSF samples from 120 individuals based on VDRL reactivity in the CSF and the clinical picture of neurosyphilis. Results: High inter-rater reliability was found among all three tests, with equivalent sensitivity and specificity. Intraclass correlation coefficient for absolute agreement was 1 for VDRL versus USR, 0.99 for VDRL versus RPR, and 0.99 for RPR versus USR. Conclusions: Rapid plasma reagin and unheated serum reagin tests were identified as excellent alternatives for neurosyphilis diagnosis.

RESUMO A sífilis é uma infecção reemergente sexualmente transmissível pelo espiroqueta Treponema pallidum, que pode penetrar precocemente no sistema nervoso central. O teste venereal disease research laboratory test (VDRL) no líquido cefalorraquidiano (LCR) é o mais amplamente utilizado para diagnóstico de neurossífilis. Avalia-se o desempenho de dois outros testes não treponêmicos (rapid plasma reagin - RPR and unheated serum reagin - USR tests) em comparação ao VDRL no LCR. Métodos: Foram analisadas amostras de LCR de 120 indivíduos com base no quadro clínico compatível com neurossifilis e reatividade no VDRL no LCR. Resultados: Os testes apresentaram elevada concordância. O coeficiente de correlação intraclasse para concordância absoluta foi de 1 para VDRL versus USR, 0,99 para VDRL versus RPR e 0,99 para RPR versus USR. Conclusões: Os testes rapid plasma reagin e unheated serum reagin foram identificados como excelentes alternativas para o diagnóstico de neurossífilis.

Neurosífilis e infección por el virus de inmunodeficiencia humana. Una puesta al día / Neurosyphilis and infection by the virus human immunodeficiency. Update

Medical literature shows that the co-infection of syphilis and human immunodeficiency virus (HIV) is increasing dramatically worldwide. HIV infection and syphilis have a synergistic relationship. Syphilis increases the risk of HIV transmission and acquisition, while HIV affects the presentation, diagnosis, progression and response to syphilis treatment. The diagnosis of syphilis is made with a non-treponemal reactive test (VDRL or RPR) confirmed with a treponemal test (FTA-ABS or MHA-TP). The opportune diagnosis of neurosyphilis is essential, particularly in the asymptomatic stages, given the high risk of serious sequels and lethality. All patients co-infected with HIV and syphilis with neurological symptoms must be studied with PL and other complementary tests. There is controversy about when to perform a lumbar puncture in co-infected patients who do not have neurological symptoms. However, there is consensus that a CD4 count lower than 350/µl or RPR title greater than 1/32 has indication for the study of cerebrospinal fluid. Therapy with penicillin G in high doses is the treatment of choice, in addition to clinical and serological follow-up that must be done to these patients. (AU)

Neurosyphilis and ocular syphilis clinical and cerebrospinal fluid characteristics: a case series / Características clínicas e liqúoricas de pacientes com neurossífilis e sífilis ocular: uma série de casos

ABSTRACT Background During the first decade of this century, a significant increase in the incidence of syphilis was documented. Objective To study clinical and laboratory characteristics of central nervous system and ocular syphilis. Methods A retrospective case series of 13 patients with a clinical and laboratory diagnosis of neurosyphilis and/or ocular syphilis who had been admitted to the Neurology and Neuro-ophthalmology Service of the Hospital de Clínicas, Federal University of Paraná. Results Nine patients had a diagnosis of neurosyphilis and two of them also had ocular syphilis. Four patients had a diagnosis of ocular syphilis alone. Among the patients with a diagnosis of neurosyphilis, six had symptomatic syphilitic meningitis, of whom one manifested as cranial nerve palsy alone, one as cranial nerve palsy plus ocular syphilis, two as transverse myelitis (syphilitic meningomyelitis), one as meningitis worsening the patient's myasthenia gravis symptoms and one as meningitis plus ocular syphilis. Additionally, we diagnosed three patients with meningovascular neurosyphilis. In the univariate analysis, patients without ocular syphilis showed greater levels of total protein and white blood cells in the cerebrospinal fluid than patients with ocular syphilis. Conclusion This Brazilian case series of patients with neurosyphilis and ocular syphilis highlights the wide variability of this disease. A high degree of diagnostic suspicion is necessary when facing neurological and ocular symptoms for rapid diagnosis and appropriate management of patients.

RESUMO Introdução Na primeira década deste século observou-se um aumento significativo da incidência de sífilis no mundo. Objetivo Estudar características clínicas e laboratoriais da sífilis no Sistema Nervoso Central e da sífilis ocular. Métodos Estudou-se, retrospectivamente, uma série de treze casos com diagnóstico clínico e laboratorial de neurossífilis e/ou sífilis ocular, admitidos aos Serviços de Neurologia ou Neuroftalmologia do Hospital de Clínicas da Universidade Federal do Paraná. Resultados Nove pacientes tiveram diagnóstico de neurosífilis e dois destes apresentaram concomitantemente sífilis ocular. Quatro pacientes tiveram somente o diagnóstico de sífilis ocular. Dos pacientes com diagnóstico de neurosífilis, seis apresentaram meningite sifilítica sintomática, dentre os quais um se apresentou com paralisia isolada de par craniano, um com paralisia de par craniano associada sífilis ocular, dois com mielite transversa (manifestação de meningomielite), um com meningite que agravou sintomas de Miastenia Gravis e um com meningite isolada associada a sífilis ocular. Houve 3 casos de neurosífilis meningovascular. Na análise univariada, pacientes sem manifestações oculares de sífilis apresentaram maiores níveis proteína total e leucócitos do que os pacientes com sífilis ocular. Conclusão Essa série brasileira de casos de pacientes com neurosífilis e sífilis ocular destaca a alta variabilidade clínica desta doença. Alto grau de suspeição diagnóstica é necessário quando em frente a sintomas neurológicos e oculares para rápido diagnóstico e adequado manejo dos pacientes.

O colapso de Turim: patografias de Nietzsche e racionalidades médicas / Turin's breakdown: Nietzsche's pathographies and medical rationalities

Resumo Aos 44 anos, após sofrer um colapso em Turim, o filósofo Friedrich Nietzsche recebeu o diagnóstico médico de neurossífilis. Devido à ausência de autópsia em seu corpo, tal diagnóstico médico vem sendo questionado historicamente. Realizou-se a revisão da literatura disponível sobre o diagnóstico médico de Nietzsche. Destacam-se três gêneros patográficos que emergiram sucessivamente como explicações para o colapso de Turim: (1) narrativas sobre a sífilis ("demoníaco-patológicas"); (2) narrativas sobre as psicoses funcionais ("heroico-proféticas"); (3) narrativas sobre outras doenças orgânicas, distintas da sífilis ("científico-realistas"). Estas últimas - que correspondem ao nosso objeto de estudo propriamente dito neste trabalho - empreendem diagnósticos retrospectivos, buscando extrair a "verdade" subjacente à doença e elucidar o "caso Nietzsche". Questionamos tal ímpeto detetivesco, exponenciado atualmente pela "medicina baseada em evidência", e denunciamos seu anacronismo. A sífilis tornou-se um fato científico somente após a morte de Nietzsche. Conclui-se que o diagnóstico por ele recebido mostra-se consistente com a racionalidade médica oitocentista e com o estatuto da sífilis como um fato cultural naquela época.

Abstract At age 44, after suffering a breakdown in Turin, philosopher Friedrich Nietzsche was diagnosed with neurosyphilis. There was no necropsy on his body, so this medical diagnosis has been questioned over the time. We conducted a literature review on the medical diagnosis of Nietzsche, which emphasizes three genres of pathographies that emerged successively as alternatives explanations for Nietzsche's breakdown in Turin: (1) narratives about syphilis ("demoniac-pathological"); (2) narratives about functional psychosis ("heroic-prophetic"); (3) other narratives about organic diseases, other than syphilis ("scientific-realistic"). The latter - which correspond to our study object in this work - undertake retrospective diagnostics, attempting to retrieve the "truth" underlying the disease and elucidate "Nietzsche's affair". We inquire this detective-like impetus, currently taken to the extreme by "evidence-based medicine", and we denounce its anachronism. Syphilis has become a scientific fact only after the death of Nietzsche. We conclude that the diagnosis he received is shown to be consistent with the nineteenth-century medical rationality and the syphilis status as a cultural fact at that time.

Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV+ patients with syphilis / El examen del líquido céfalo raquídeo puede ser útil en el diagnóstico de neurosífilis en pacientes VIH + asintomáticos con sífilis

ABSTRACT Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF), especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL), regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA) titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients.

RESUMO La punción lumbar (PL) en pacientes VIH+ neurológicamente asintomáticos es controversial. Existen diferentes criterios para detectar en el líquido cefalorraquídeo (LCR) neurosífilis (NS): el examen Venereal Disease Research Laboratory (VDRL) en primer lugar, en caso de negatividad: la celularidad y el tenor de proteinas. Sin embargo el diagnóstico de NS puede ser sostenido a pesar de la negatividad de las técnicas mencionadas. La titulación del Treponema pallidum hemagglutination assay (TPHA) y la aplicación del índice de TPHA en Albúmina e Ig G mejoran la sensibilidad asociando elevado grado de especificidad. 32 pacientes fueron seleccionados para este estudio, el VDRL fue positivo en 5. El diagnóstico se elevó a 14 cuando se sumaron el resto de las técnicas. No se evidenció que la celularidad y el aumento de proteínas fueran herramientas auxiliares para el diagnóstico. De acuerdo a nuestro trabajo el estudio del LCR con las técnicas señaladas puede ser de utilidad en el diagnóstico de NS en estos pacientes.

Síndromes neuropsiquiátricos causados por treponema pallidum / Neuropsychiatric syndromes caused by treponema pallidum

"Neumsyphilis" (NS) refers to infection of the central nervous system (CNS) caused by Treponema pallidum. NS can occur at any time after initial infection (syphilitic chancre). Most common early course of NS involve the cerebrospinal fluid (CSF), meninges, vasculature and uvea: asymptomatic meningitis, symptomatic meningitis, meningovascular disease. Late disease after 10 years, generally involves the brain and spinal cord parenchyma as general paralysis of the insane and tabes dorsalis. Each form has characteristic neuropsychiatric syndromes, but in some cases there is overlap between the clinical, and radiologic findings. Other forms such as gummas, diverse psychiatric manifestations and syphilitic amyotrophy, have also been described. Diagnosis and therapy are based on the cytochemical study of CSF, serology plays a key role (non-treponemal and treponemal tests). The most effective treatment is penicillin. This reviews also describes neuropathology and the atypical or masked forms of this complex disease including co-infection by human immunodeficiency virus.

"Neurosífilis" (NS) se refiere a las infecciones del sistema nervioso central (SNC) causadas por Treponema pallidum. La NS puede presentarse en cualquier momento después de la infección primaria o chancro sifilítico. Las formas tempranas implican la invasión del líquido cefalorraquídeo (LCR), las meninges, la vasculatura y la uvea: meningitis asintomática, meningitis sintomática, enfermedad cerebro vascular, uveítis anterior. Las formas tardías después de los 10 años, se caracterizan por la penetración del parénquima cerebral y/o la médula espinal, como demencia paralítica progresiva y tabes dorsal. Cada forma genera síndromes neuropsiquiátricos característicos, pero en algunos casos hay una sobreposición de los hallazgos clínico-radiológicos. Se describe también los gomas, alteraciones psiquiátricas diversas y la amiotrofia. El diagnóstico y la evolución del tratamiento se basan en el estudio citoquímico del LCR, pero la serología juegan un papel muy importante (análisis no-treponémicos y treponémicos). El tratamiento más recomendado son las penicilinas. Esta revisión repasa también la neuropatología, y las formas atípicas o enmascaradas de esta enfermedad compleja, incluyendo la coinfección por el virus de la inmunodeficiencia humana.

Indicação de punção lombar para diagnóstico da neurossífilis / Indication of lumbar puncture for neurosyphilis diagnosis

A sífilis é um agravo infectocontagioso causado pelo Treponema pallidum, de transmissão predominantemente sexual, que afeta 12 milhões de pessoas por ano no mundo. Se não curada em suas fases iniciais, predispõe a complicações potencialmente graves. Uma dessas complicações é a neurossífilis, caracterizada pela invasão do sistema nervoso central pelo T. Pallidum em qualquer fase da história natural da infecção, cuja mortalidade ultrapassa 60%. Em pessoas com HIV, essa complicação pode ser mais frequente, surgir após um menor período de latência e ser mais agressiva. Na maioria das vezes, a neurossífilis é assintomática ou se apresenta por meio de manifestações clínicas pouco específicas que demandam alto índice de suspeição e propedêutica laboratorial invasiva. O diagnóstico é feito através de provas sorológicas ou de biologia molecular no líquor. A controvérsia é sobre a indicação desse diagnóstico e respectivo tratamento nos casos assintomáticos, principalmente em se tratando de pessoas que vivem com o HIV. Esta revisão narrativa da literatura concluiu que a punção lombar propedêutica da neurossífilis está indicada em pessoas que apresentam sororreagência ao VDRL, associado a uma ou mais das seguintes condições: manifestações neurológicas na esfera motora, sensitiva ou cognitiva; sintomatologia sifilítica ou VDRL maior que 1:8 pós-tratamento, descartada reinfecção; pessoas com HIV na presença de CD4 menor que 351 células/mm3 e VDRL maior ou igual a 1:32; e evidência de doença sifilítica terciária não neurológica em atividade (goma ou aortite). Feito o diagnóstico a partir desses critérios, o tratamento específico deverá ser administrado mesmo nos casos assintomáticos.

Syphilis is an infect-contagious injury caused by Treponema pallidum, of predominantly sexual transmission, which affects 12 million people worldwide each year. If not cured in its early stages, predisposes to potentially serious complications. One of the complications is neurosyphilis, characterized by the invasion of the central nervous system by T. pallidum in any phase of the natural history of the disease, whose mortality exceeds 60%. In people with HIV, this complication may be more frequent, arising after a shorter period of latency and also be more aggressive. Most often, neurosyphilis is asymptomatic or presents itself by means of little specific clinical manifestations, which require high index of suspicion and invasive laboratory propaedeutics. The diagnosis is made by serological tests or molecular biology study on the cerebrospinal fluid. The controversy is about the indication of this diagnosis and respective treatment in asymptomatic cases, mainly in people living with HIV. This narrative review of the literature concluded that propaedeutic lumbar puncture of neurosyphilis is recommended for people who have serum-reactivity to the VDRL, associated with one or more of the following conditions: neurological manifestations on motor, sensory or cognitive sphere; syphilitic symptoms or VDRL greater than 1:8 post-treatment, discarded reinfection; persons with HIV at the presence of CD4 less than 351 cells/mm3 and VDRL greater than or equal to 1:32; and evidence of no neurological tertiary syphilitic disease inactivity (gumma or aortitis). Made the diagnose from these criteria, specific treatment should be given even in asymptomatic cases.

Ocular syphilis in spouses: diagnosis, treatment and medical confidentiality / Sífilis ocular em cônjuges: diagnóstico, tratamento e sigilo médico

The aim of this paper is to report two cases of neurosyphilis and uveitis diagnosed by an ophthalmologist in an immunocompetent couple. In addition to reporting cases the authors discuss ethical issues of communication of diagnosis to partners of patients (AU)

O objetivo do presente artigo é relatar dois casos de neurosífilis e uveíte diagnosticados por oftalmologista em casal imunocompetente. Além de relatar os casos, os autores discutem questões éticas da comunicação do diagnóstico aos parceiros dos pacientes (AU)

Syphilitic dementia presenting with Adie's tonic pupil and mesial temporal lobes hyperintensities / Demência sifilítica apresentando pupila tônica de Adie e hiperintensidades temporais mesiais

Syphilis became a rare cause of dementia in the present days. Screeningtests for syphilis are no longer recommended according to 2001.American Academy of Neurology guidelines. On the other hand, as itmay represent a potentially treatable cause in developing countries,the Academia Brasileira de Neurologia recommends laboratory screeningfor syphilis in patients with dementia. The diagnosis of neurosyphilisis established with basis on the clinical setting, along withtreponemal and non-treponemal serum antibodies, and cerebrospinalfluid pattern. Magnetic resonance imaging generally reveals cortical atrophy. Focal signs in the temporal lobes are rarely seen. A case of a young man diagnosed with neurosyphilis is presented, on the basis of neuropsychiatric symptoms, uncommon pupillary changes (Adie's tonic pupil), CSF with positive FTA-abs, and increased IgG index, and additionally mesial temporal lobes hypersignal changes.

Considera-se neurossífilis uma causa rara de demência atualmente.Testes para investigação de sífilis não são mais recomendados deacordo com as orientações da Academia Americana de Neurologia,de 2001. Por outro lado, como pode representar uma causa potencialmente tratável, a Academia Brasileira de Neurologia recomendaa investigação de sífilis em pacientes com demência. O diagnósticode neurossífilis é estabelecido pelo quadro clínico em associaçãocom anticorpos treponêmicos e não treponêmicos, e exame de LCR.Ressonância magnética revela, em geral, atrofia cortical. Presençasde sinais focais em lobos temporais são consideradas raras. É apresentado caso de homem jovem com diagnóstico de neurossífilis combase nas manifestações neuropsiquiátricas, alteração incomum aoexame pupilar (pupila de tônica de Adie), LCR com FTA-abs positivoe índice de IgG elevado, e ainda hipersinal nos lobos temporais mesiais.

Neurossífilis: uma breve revisão / Neurosyphilis: a brief review

A neurossífilis (NS) designa todas as formas de comprometimento do sistema nervoso central (SNC) causadas pela bactéria Treponema pallidum. Em pacientes imunocompetentes, ocorre principalmente no estádio terciário da sífilis (embora suceda em outros estádios), acometendo apenas 10 porcento dos pacientes com infecção primária não tratada. Apesar de um decréscimo significativo na incidência de neurossífilis nas últimas três décadas, a invasão do sistema nervoso humano ainda ocorre e a apresentação clínica não segue a evolução tradicional da era pré-antibiótica. Observa-se, atualmente, que a NS pode apresentar quadros clínicos muito similares aos de outras enfermidades do sistema nervoso, podendo ser confundida, mesmo após anos de acompanhamento, com doenças neurológicas ou psiquiátricas. Neste trabalho, fizemos uma revisão histórica, conceitual, epidemiológica, clínica e diagnóstica com o objetivo de ampliar o conhecimento sobre esta doença e melhorar a sua compreensão...

Neurosyphilis (NS) designates all the adverse effects on the central nervous system (CNS) caused by Treponema pallidum. It occurs at the third stage of syphilis in about 10 percent of patients with untreated primary infection. Despite a significant decrease in the incidence of neurosyphilis during the last three decades, the invasion of the human nervous system still takes place and the clinical presentation does not follow the traditional evolution of the pre-antibiotic era. At present, it is observed that NS may present clinical features very similar to those of other illnesses of the nervous system, and can be mistaken, even after years of follow-up, for neurological or psychiatric illnesses. In this work, we conducted an historical, epidemiological, conceptual, clinical and diagnostic review, with the purpose of expanding the knowledge and improving the understanding of this disease...

Manifestaciones neuropsiquiátricas de la neurolúes: presentación de un caso de parálisis general neurosifilítica / Neuropsychiatric manifestations of neurosyphilis: a case of general paresis

Introducción: La parálisis general se debe a la lesión tardía y degenerativa de la sustancia gris cerebral por el Treponema pallidum, caracterizada por demencia, signos oculares, neurológicos y humorales. Es frecuente su comienzo con manifestaciones delictuales. Caso clínico: Describimos el caso de un paciente de 61 años, masculino, sin antecedentes. Ingresa para comprobar imputabilidad (asesinó a su primo); atento, vigil, desorientado, disártrico, musita, pensamiento detallista y concreto. No sabe causa de acusación ni argumenta en su defensa; sin productividad psicótica. Signos vitales estables, exámenes de laboratorio normales. Se ingresa con diagnóstico de deterioro psicoorgánico. Se maneja con clorpromazina 12,5 mg en la mañana, tarde y 50 mg noche. Evoluciona con temblor, rigidez, enlentecimiento, alucinaciones visuales, auditivas y soliloquios. Por sospecha de impregnación se suspende la clorpromazina, se solicitan exámenes y se evaluó por neurólogo. Inatento, apráxico, marcha con aumento de base de sustentación, adiadococinesia, dismetría, Romberg (+) y pupilas de Argyll Robertson. VDRL de 1/512 sérico y 1/8 en el LCR. Se diagnostica parálisis general neurosifilítica. Se maneja con penicilina G acuosa 6 millones UI c/ 6 h IV por 14 días y olanzapina 20 mg c/noche con respuesta parcial. Conclusión: La parálisis general es poco frecuente pero debe ser sospechada en pacientes de edad media con demencia y signos característicos neuro-oculares.

Introduction: General Paresis is caused by a late and degenerative injury by Treponema pallidum to cerebral grey matter, characterized by dementia, as well as ocular, neurological, and mood changes. It generally first manifests in criminal activity. Clinical case: We describe the case of a 61-year-old male patient, with no past medical history. Admitted to prove imputability (he assasinated his cousin). Attentive, alert, disoriented. Dysarthria and murmured speech. Highly detailed and concrete thinking. He does not know the cause of the accusation, and he does not argue in his defense neither. No psychotic symptoms. Stable vital signs and normal laboratory exams. Admitted with a diagnosis of psycho-organic deterioration. Controlled with clorpromazine 12.5 mg BID and 50 mg/night. Evolution with tremor, rigidity, slowing. Visual and auditory hallucinations and soliloquy. On suspicion of neuroleptic impregnation we discontinue clorpromazina. Laboratory tests and neurologist evaluationare requested. Inattentive, apraxia, adiadochokinesia, dysmetria, Romberg (+) and Argyll Robertson pupils. Serum VDRL 1/512 and CSF1/8. Diagnose general paresis (neurospyhilisis). Treatment with aqueous penicillin G 6 million Ul every 6 hours IV for 14 days and olanzapine 20 mg every night with partial response. Conclusion: General paresis is infrequent but should be suspected in middle-aged patients with dementia and characteristic neuro-ocular signs.

Parálisis general sifilítica: presentación de 5 casos / Paretic neurosyphilis: report of five patients

We report five male patients, aged 35 to 63 years who suffered from paretic neurosyphilis. The clinical course was that of a subacute dementia with a frontal syndrome, with more apathy than euphoria. All were HIV negative and four were heterosexual. In all, the cerebrospinal fluid had a mononuclear pleocytosis and a positive VDRL. EEG was abnormal in the 3 cases in whom it was performed. One patient in whom a brain angiography was performed, had images of vasculitis. Treatment with 18-24 million units of penicillin per day during two weeks or more, was partially effective.

Diagnóstico de la infección por Treponema pallidum en pacientes con sífilis temprana y neurosífilis mediante reacción de la polimerasa en cadena / 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 tpN47gene. Twenty out of 21 mucocutaneous samples from patients diagnosed with ES were positive by PCR, with a clinical sensitivity of 95 percent. Four out of 8 CSF samples from patients previously diagnosed with NS were positive by PCR, with a clinical sensitivity of 50 percent. The clinical specificity for both ES and NS was 100 percent. 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.

La sífilis es una enfermedad de transmisión sexual producida por Treponema pallidum, cuyo diagnóstico se realiza presuntivamente basándose en aspectos clínicos y análisis de especificidad limitada. La reacción de la polimerasa en cadena (RPC) ha sido planteada como una alternativa diagnóstica de mayor sensibilidad y especificidad. El objetivo de este trabajo fue validar una RPC para el diagnóstico de sífilis temprana (ST) y neurosífilis (NS). Se utilizaron muestras de lesiones muco-cutáneas y de LCR de pacientes con sospecha de cursar ST y NS respectivamente, previamente diagnosticados, utilizando un estándar de oro ampliado. La RPC fue realizada con partidores dirigidos al gen tpN47. De las 21 muestras de pacientes con ST, la RPC resultó positiva en 20, lo que resulta en una sensibilidad clínica de 95 por ciento. De las 8 muestras de pacientes con NS, la RPC resultó positiva en 4, obteniéndose una sensibilidad clínica de 50 por ciento. La especificidad clínica para ST y NS fue de 100 por ciento. La excelente sensibilidad y especificidad de la RPC para muestras muco-cutáneas permitió la exitosa implementación de este análisis en nuestro laboratorio para el diagnóstico de rutina. Si bien la sensibilidad de la RPC en LCR es baja, es muy útil para apoyar el diagnóstico clínico.

Neurosífilis meningovascular y gomatosa cerebral concomitante, en paciente seronegativo para virus de inmunodeficiencia humana / Meningovascular neurosyphilis and concomitant syphilitic gummata in hiv-seronegative patients

Neurosyphilis (NS) is caused by the presence of Treponema Pallidum (TP) spirochete within the Central Nervous System (CNS), mainly affecting the meninges and cerebrospinal fluid (CSF). 5 percent to 10 percent of untreated syphilitic patients are deemed to develop symptomatic NSÕ. Its incidence and clinical spectrum have changed over the years with prevalence of early clinical stages of meningitic and meningovascular (MV) NS and exceptional occurrence of late clinical stages (tabes dorsalis, general paresis, and gummata) in the age of antibiotics. The case under analysis deals with aggressive MV and concomitant brain gumma (BG) NS. The case subject is a human inmunodeficiency virus (HIV)-seronegative, 44-year-old woman with 2-year symptomatic latency. Her medical record showed recurrent sensorimotor vascular involvement, fast cognitive damage and chronic, daily cephalea. She met clinical diagnosis, cerebrospinal fluid and serologic criteria for NS. Brain computerized tomography (CT) and magnetic resonance (MR) reported lenticulostriate artery infarction and bilateral ganglionic syphilitic gummata. She underwent Penicillin G-based treatment, making progress with neurological, cognitive-motor sequelae. Although NS has anticipated and speeded up its several clinical stages in connection with HIV/Syphilis co-infection, the peculiarity of this case is the concurrence of early and late NS manifestations in HIV-seronegative patient. The conclusion is that NS is a disease that still prevails and that appropriate diagnosis and treatment prevent irreversible neurological sequelae.

La Neurosífilis (NS) es causada por la invasión del Sistema Nervioso Central (SNC) por la espiroqueta Treponema Pallidum (TP), afectando primariamente las meninges y líquido cefalorraquídeo. Entre 5 a 10 por ciento de los pacientes sifilíticos no tratados desarrollarán una NS sintomáticaÕ. Su incidencia y espectro clínico ha cambiado a lo largo del tiempo, siendo las formas clínicas precoces meníngea y meningovascular (MV) las más prevalentes. En contraste, las formas tardías (tabes dorsal, parálisis general y gomas) son de ocurrencia excepcional en la era antibiótica. Se analiza un caso de NS menigovascular y gomas cerebrales concomitantes, de curso clínico agresivo. En una mujer de 44 años, seronegativa para virus de inmunodeficiencia humana (VIH), con latencia sintomática de dos años. Presentaba una historia de focalidad sensitivo-motor de perfil vascular recurrente, rápido deterioro cognitivo-motor y cefalea crónica diaria. Cumplía criterios diagnósticos clínicos, licuorales y serológicos para NS. La Tomografía computada (TC) y Resonancia Magnética (RM) cerebral mostró infartos arteriolares lentículo-estriados y gomas sifilíticas ganglionares bilaterales. Recibió tratamiento con Penicilina G, evolucionando con secuelas neurológicas cognitivas-motoras. Si bien, la NS actualmente, ha anticipado y acelerado sus diferentes formas clínicas en relación a co-infección VIH/Sífilis. Lo llamativo de este caso, es la presentación concomitante de con manifestaciones precoces y tardías de NS en paciente VIH seronegativo. Se concluye que la NS sigue siendo una enfermedad vigente y su diagnóstico y tratamiento oportuno previene secuelas neurológicas irreversibles.

A importância de incluir neurossífilis no diagnóstico diferencial de pacientes com déficit cognitivo e alteração do comportamento / The importance of including neurosyphilis in the differential diagnosis of patients with cognitive decline and behavior disturbances

É resultado da infecção do cérebro, das meninges ou medula espinhal pelo Treponema pallidum e desenvolve-se em cerca de 25-40% das pessoas que não são tratadas para a sífilis. A demência por neurossífilis é uma manifestação tardia da sífilis e era causa frequente de deterioração cognitiva antes do aparecimento e da disseminação do uso da penicilina no tratamento das fases iniciais da doença. Embora incomum nos dias de hoje, a demência por neurossífilis ainda constitui diagnóstico diferencial a considerar-se, diante de síndromes demenciais atípicas ou com manifestações frontais, particularmente em populações menos favorecidas socialmente. Esse caso destaca a importância do diagnóstico precoce da neurossífilis, e que os médicos devem se alertar para a possibilidade desta doença em pacientes que apresentam demência, principalmente por pertencer ao grupo das demências potencialmente reversíveis,pois o tratamento adequado pode reverter o declínio cognitivo. E ainda, pelo aumento no número de casos de sífilis na última década, particularmente pela coinfecção com HIV, que pode acelerar o curso e alterar a resposta ao tratamento da sífilis. Este aumento da incidência de sífilis, observado também na Europa e nos Estados Unidos, poderá traduzir-se num acréscimo do número de casos de neurossífilis observados na prática clínica.

Neurosyphilis results from infection of the brain, meninges or spinal cord by Treponema pallidum and develops in about 25-40% of persons who are not treated for syphilis. Dementia by neurosyphilis is a late manifestation of syphilis and was a frequent cause of dementia before the advent and widespread use of penicillin in the treatment of early stages of the disease. Although uncommon today, dementia of neurosyphilis still a differential diagnosis to consider in the face of atypical dementia or with manifestations front, particularly in socially disadvantaged populations socially. This case underscores the importance of early diagnosis of neurosyphilis, which clinicians should alert the possibility of neurosyphilis in patients who present with dementia, mainly belonging to the group of potentially reversible dementias, because proper treatment can reverse cognitive decline. And also, by increasing the number of syphilis cases in the last decade, particularly in combination with HIV, which can acelerate the course and alter the response to treatment of syphilis. This increasedincidence of syphilis, also observed in Europe and the United States, could result in an increase in the number of cases of neurosyphilis observed in clinical practice.