Multiple cerebral syphilitic gummas mimicking brain tumor in a non-HIV-infected patient: A case report.

We present a unique case of symptomatic early neurosyphilis in a non-HIV-infected patient. A 47-year-old man with a history of diabetes mellitus presented with generalized seizures. He did not manifest any neurological deficits. At first, multiple brain tumors were suspected based on findings from magnetic resonance imaging of the brain. However, serological and cerebrospinal fluid tests for syphilis yielded positive results, and the masses were reduced using amoxicillin. Multiple cerebral syphilitic gummas were therefore diagnosed. High-dose penicillin therapy was initiated and syphilitic gummas disappeared after five months. Treponema pallidum could invade the central nervous system at an early phase, and sometimes may be difficult to distinguish from malignant brain tumor. If intracranial lesions are identified in a syphilis-infected patient, cerebral syphilitic gumma should be considered as a differential diagnosis.

Síndrome extrapiramidal con corea generalizada como forma de presentación atípica de leucoencefalopatía multifocal progresiva / Extrapyramidal syndrome with generalized chorea as an atypical presentation of progressive multifocal leukoencephalopathy

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Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

BACKGROUND: Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS: Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE: Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

Penicillin Encephalopathy: An Unlikely Adversary in the Treatment of Neurosyphilis--Case Report and Review of the Literature.

UNLABELLED: Penicillin encephalopathy is a rare, potentially reversible phenomenon of drug-induced neurotoxicity. CASE: A 65-year-old female with a history of HIV was admitted with a three-day history of worsening headache, confusion, and lethargy. On examination she was awake but confused. Cerebrospinal fluid (CSF) and serum venereal disease research laboratory (VDRL) test returned positive and the patient was started on intravenous penicillin G with probenecid. On the second day of therapy, she developed myoclonic jerking, consistent with penicillin neurotoxicity. Repeat labs also showed new onset renal failure. Penicillin and probenecid therapy were stopped with a resolution of symptoms. Subsequently, therapy without probenecid was reinstituted uneventfully. DISCUSSION: Herein, we describe a female who developed penicillin neurotoxicity after initiation of intravenous penicillin therapy with probenecid for neurosyphilis. It is important that penicillin-induced toxicity be considered if characteristic myoclonic movements accompany encephalopathy. The presence of coexistent renal compromise should heighten the vigilance of clinicians.

Oral doxycycline for treatment of neurosyphilis in two patients infected with human immunodeficiency virus.

The frequency of syphilis has been increasing during the past 5 years primarily among men who have sex with men, many of whom are infected with the human immunodeficiency virus (HIV). Data on treatment options other than intravenous or intramuscular penicillin for syphilis are very limited. We describe two HIV-infected patients with asymptomatic neurosyphilis who were successfully treated with oral doxycycline. The first patient was a 45-year-old Hispanic man with well-suppressed HIV RNA who had a positive Venereal Disease Research Laboratory (VDRL) titer of 1:128. His cerebral spinal fluid (CSF) revealed a positive VDRL titer of 1:16, and an elevated white blood cell count of 96 cells/mm(3) and protein level of 89 mg/dl. He received high-dose doxycycline 200 mg twice/day for 28 days. Two months later, his CSF VDRL titer, white blood cell count, and protein level decreased to 1:4, 5 cells/mm(3), and 60 mg/dl, respectively. The second patient was a 37-year-old Caucasian man with complications from acquired immunodeficiency disease. A routine VDRL titer was found to be 1:64. Although the CSF VDRL was nonreactive, both his white blood cell count and protein level were elevated at 29 cells/mm(3) and 46 mg/dl, respectively. High-dose doxycycline 200 mg twice/day was prescribed for 28 days. Three months later, the patient's VDRL titer decreased to 1:2; his CSF white blood cell count decreased significantly to 1 cell/mm(3), and his protein level was within normal limits. Clinicians should be aware that an extended course of high-dose, oral doxycycline may be an effective and safe alternative regimen to intravenous or intramuscular penicillin, without requiring hospitalization or home health care, for the treatment of neurosyphilis in HIV-infected patients. Prospective trials are needed to assess the long-term efficacy oral doxycycline for neurosyphilis.

When infections collide--gummatous syphilis in an HIV-infected individual.

Syphilis and HIV are both transmitted sexually and have emerged as important co-pathogens with reciprocal augmentation in transmission and disease progression. HIV-positive patients tend to experience more aggressive symptomatology due to syphilis and are at greater risk of developing neurological disease. Similarly, standard therapy for syphilis may be inadequate in HIV-positive individual suggesting intensified treatment regimens may be required along with close follow-up. We report here the case of a 50-year-old HIV-positive male presenting with an unusual constellation of neurological findings. Although he had been treated appropriately 10 years previously for primary syphilis, investigations revealed multiple current intracranial gummas. Treatment with high-dose intravenous penicillin G resulted in clinical and radiographic resolution. Given the broad differential for HIV-positive patients presenting with neurological symptoms, the clinician must maintain a high index of suspicion for syphilis known for its varied and at times unusual manifestations. Further, prior treatment of syphilis does not ensure cure and so syphilis must be considered irrespective of treatment history.

Neurosyphilis presenting as schizophrenialike psychosis.

OBJECTIVE: The authors present a 30-year-old pregnant and previously healthy woman with sudden onset of agitation, delusions, and frontal lobe dementia. Serum and cerebrospinal fluid findings revealed the presence of untreated syphilis. BACKGROUND: Neurosyphilis can present a variety of behavioral symptoms, including mania, depression, and psychosis. METHOD: A neuropsychiatric and neurologic workup was performed before the start of antibiotic treatment. The status of the patient was observed throughout the course of her hospital stay for 7 months. Additionally, a neuropsychological evaluation was administered before treatment, and 2 weeks and 4 months after treatment. RESULTS: After treatment of neurosyphilis, steady improvements were noted in psychotic and cognitive symptoms. By the end of 7 months, and after discontinuation of antipsychotic medication, no psychiatric symptoms were evident. CONCLUSIONS: This case emphasizes the importance of considering neurosyphilis in the differential diagnosis of acute psychosis. Furthermore, this case shows the dramatic improvement in psychiatric symptoms and cognitive dysfunction in response to the treatment of neurosyphilis.

Oligosymptomatic neurosyphilis with false negative CSF-VDRL in HIV-infected individuals?

The true prevalence of neurosyphilis in HIV-infection is unknown, since a sufficiently sensitive and specific test is lacking. In a prospective study we found reactive serum TPHA and FTA-ABS IgG tests in 95 (31%) of 307 HIV-infected patients. Three of 11 patients with latent syphilis revealed reactive CSF-VDRL tests, six others only demonstrated CSF abnormalities. Resolution of CSF abnormalities during a six month follow up after high dose antibiotic therapy led to the diagnosis of oligosymptomatic or asymptomatic neurosyphilis in all nine patients. Thus, the specificity of the CSF-VDRL was 100%, but the sensitivity was only 33%. The overall prevalence of neurosyphilis was 2.9%, increasing to 9.5% in patients with a reactive serum TPHA. Our study emphasizes the importance of antibiotic therapy for presumptive neurosyphilis in HIV-infected patients with latent syphilis and CSF abnormalities but nonreactive CSF-VDRL tests, even if they are neurologically asymptomatic or present with complaints inconclusive of neurosyphilis.

The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS: Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS: In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS: In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

CT, MR, and SPECT findings in a general paresis.

CNS changes in a case with general paresis were investigated by X-ray computed tomography (CT), Magnetic resonance (MR), and single photon emission computed tomography (SPECT). CT and MR showed a mild degree of diffuse cortical atrophy and the dilatation of lateral ventricles with no signs of ischemic lesions or inflammations. On the other hand, SPECT using 123I-N-isopropyl-p-iodoamphetamine (123I-IMP demonstrated marked reduction of the cerebral blood flow especially in the bilateral frontal and temporal cortices. Moreover, the reduction of the blood flow was significantly improved after the antisyphilitic therapy, correlated with the improvement of the mental disorders. These observations suggested that the SPECT is a useful method to evaluate the brain dysfunctions, and to assess the effect of antisyphilitic therapy in the patients with general paresis.

[Development of dementia]. / Dementielle Entwicklung.

A 67-year old male patient was admitted to our clinic because of slowly developing dementia. Severe dysfunction of memory, confusional states and urinary incontinence were observed. A diagnosis of general paresis was made by positive serology for syphilis and CSF examination. The patient's condition improved markedly after high-dose penicillin G treatment.

[A case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies].

Here we described a case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies. A 56-year-old man was admitted because of left facial palsy and hearing loss of bilateral ears. He had a penile chancre five months before admission. Cerebrospinal fluid examination showed high pressure, pleocytosis predominantly with mononuclear cells and high protein content. STS and TPHA of serum and CSF were positive. High dose penicillin G was effective, and he was discharged with only mild hearing loss in the left. Considering the penetration of penicillin G into the CSF and the minimum fully treponemicidal concentration of penicillin, the administration of large doses of aqueous penicillin G intravenously or intramuscularly was effective in such a case to prevent permanent deafness, though CDC recommends relatively low dose.

[Neurosyphilis in HIV infection: persistence after high-dose penicillin therapy]. / Neurosyphilis bei HIV-Infektion. Persistenz nach hochdosierter Penicillintherapie.

Ten years after treatment of secondary syphilis a 44-year-old otherwise asymptomatic HIV-infected patient developed acute meningovascular syphilis with multifocal manifestations and neurological deficit. Whether it was a reactivation or new infection could not be established. High-dosage intravenous penicillin treatment failed to eliminate completely the CNS disease process. Inflammatory CSF findings with pleocytosis and demonstration of intrathecally formed specific antibodies, still present a year later, made it likely that the syphilitic infection was persisting. The concurrent HIV infection probably aggravated the course of the neurosyphilis. Serological tests for syphilis should be done in every HIV-infected patient, followed by CSF examination if the results are suspicious. Analogous to the known opportunistic CNS infections, a more extensive period of treatment should also be considered in the case of neurosyphilis in HIV-infected patients.

[High-dose intravenous penicillin therapy in neurosyphilis: study of 62 cases. II. Evaluation of cerebrospinal fluid]. / Penicilinoterapia intravenosa em altas doses na neurossífilis: Estudo de 62 casos. II. Avaliação do líqüido cefalorraqueano.

Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Forty-one patients had pleocytosis in the CSF before treatment. Six months and twelve or more months later, abnormal cell count was observed in 4 (9.8%) and in 3 patients (7.3%), respectively. The CSF protein level and the titers of Wassermann reaction in the CSF decreased slowly after treatment. The gammaglobulin concentration of the CSF and the immunoglobulin production inside the blood-brain barrier were still increased beyond the first year after treatment. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with lesser doses of intramuscular penicillin that were reported in the literature.

[High-dose intravenous penicillin therapy in neurosyphilis. III. Evaluation of antitreponemal antibodies of the IgM class in cerebrospinal fluid and serum]. / Penicilinoterapia intravenosa em altas doses na neurossífilis. III. Avaliação de anticorpos antitreponêmicos da classe IgM no líqüido cefalorraqueano e no soro.

IgM antibodies against Treponema pallidum were investigated in the serum and in the CSF of 9 patients with symptomatic neurosyphilis, before the treatment and in several occasions after the treatment. Tests used were the FTA-Abs test, the IgM-solid phase hemadsorption test and an IgM-Elisa test. Titers of reactions decreased after treatment but they were still reactive in the blood and in the CSF during the second year after the treatment.

Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos: II. Avaliaçäo do líquido cefalorraqueano / High-dose intravenous penicillin G in the treatment of neurosyphilis: a study of 62 patients: II. Cerebrospinal fluid evaluation

Sessenta e dois casos de neurossífilis sintomática foram tratados com penicilina G, na dose diária de 20 ou 24 milhöes de UI, por via intravenosa, durante 15 a 30 dias. O tempo médio de acompanhamento foi de 30 meses. Antes do tratamento, 41 pacientes apresentavam pleocitose ao exame do LCR. Seis meses e doze ou mais meses depois, foi constatada pleocitose em 4 (9,8%) e em 3 pacientes (7,3%), respectivamente. A proteinorraquia e os títulos das reaçöes de Wassermann do soro e do LCR reduziram-se lentamente depois do tratamento. O teor de globulinas gama do LCR e os índices de imunoproduçäo local do sistema LCR ainda encontravam-se elevados depois do primeiro ano após tratamento. Os resultados da penicilinoterapia intravenosa em altas doses constatados neste estudo näo diferiram daqueles obtidos com penicilinoterapia intramuscular em baixa doses registrados na literatura

Penicillin concentrations in serum and CSF during high-dose intravenous treatment for neurosyphilis.

Eight neurosyphilitic patients (two asymptomatic, six symptomatic) were treated with intravenously administered aqueous penicillin G, 0.15 million IU/kg body weight/24 hrs for 15 days. On the 8th day of treatment, penicillin concentrations were determined in serum and CSF samples collected at hourly intervals over a period of 8 hours, using a microbiological assay method. Serum concentrations ranged from 0.26 to 100 mg/l, while CSF concentrations ranged from 0.062 to 3.0 mg/l. These results indicate that, by ensuring penicillin concentrations in CSF, which are continuously above the minimal fully treponemicidal concentration during the course of treatment, this treatment regimen should provide an adequate therapy for asymptomatic and symptomatic neurosyphilis.

Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos; I. Avaliaçäo clínica / High-dose intravenous penicillin treatment in neurosyphilis: a study of 62 patients; I. Clinical evaluation

Sessenta e dois casos de neurossífilis sintomática foram tratados com penicilina G, na dose diária de 20 ou 24 milhöes de UI, por via intravenosa, durante 15 a 30 dias. O tempo médio de acompanhamento após o tratamento foi de 30 meses. Aparecimento de novos sinais neurológicos depois do tratamento foi constatado em 13 pacientes. As formas clínicas apresentadas por esses pacientes eram: paralisia geral progressiva (9), taboparalisia (2), tabes dorsal (1) e neurossífilis meningovascular (1). Trinta e seis pacientes (58,1%) apresentaram melhora do quadro clínico, 22 (35,5%) näo sofreram alteraçöes e 4 pacientes (6,4%) pioraram clinicamente depois do tratamento. Em dois pacientes houve progressäo para outras formas de neurossífilis. Os resultados clínicos da penicilinoterapia intravenosa constatados neste estudo näo diferiram daqueles obtidos com penicilinoterapia intramuscular clássica registrados na literatura