Clinical characteristics, diagnosis, and predictors of neurosyphilis patients with human immunodeficiency virus co-infection: A retrospective study at infectious diseases hospitals in two cities of China.

ABSTRACT: This study aimed to compare between the clinical and laboratory characteristics of neurosyphilis and those of syphilis in human immunodeficiency virus (HIV) positive and explore the risk factors associated with the occurrence of neurosyphilis in the HIV infected.In-patients diagnosed with HIV and syphilis co-infection who underwent a lumbar puncture and completed cerebrospinal fluid (CSF) examination were divided into neurosyphilis group and syphilis group. The demographic characteristics, symptoms and signs, and laboratory tests of the 2 groups were comparatively analyzed. Logistic regression analysis was used to explore the risk factors associated with the occurrence of neurosyphilis.Among 81 patients, 33 patients were assigned to the neurosyphilis group, and 48 to the syphilis group. There were no significant differences in the age, gender, marital status, acquired immunodeficiency syndrome course, opportunistic infections, serum HIV viral load, and history of syphilis treatment. The difference in HIV transmission route between the 2 groups was statistically significant (P = .010), and the patients from the neurosyphilis group were mainly infected via heterosexual contact. The proportion of serum toludine red unheated serum test (TRUST) titer ≥1:16 in the neurosyphilis group were 78.8%, which was significantly higher compared to the syphilis group (48.9%). The level of CSF white blood cell count, CSF protein, and CSF HIV viral load in the neurosyphilis group were significantly higher than those of the syphilis group. The proportion of patients with neurological symptoms and signs in the neurosyphilis group was significantly higher compared to the syphilis group (P < .001). Multivariate logistic regression analysis showed that heterosexual contact transmission route, not received antiretroviral therapy, lower CD4 cell count and higher serum TRUST titer, untreated with syphilis, and neurological symptoms and signs were risk factors associated with the occurrence of neurosyphilis.The serum TRUST titer, CSF white blood cell count, CSF protein level, CSF HIV viral load, and the percentage of neurological symptoms and signs in the neurosyphilis group were higher. Heterosexual transmission route, not received antiretroviral therapy, and untreated with syphilis prompted the possibility of neurosyphilis occurrence.

Cognitive impairment in syphilis: Does treatment based on cerebrospinal fluid analysis improve outcome?

BACKGROUND: Individuals with previous syphilis may experience cognitive impairment. The goal of this study was to determine if those at high risk for laboratory-defined neurosyphilis are cognitively impaired, and whether treatment based on cerebrospinal fluid (CSF) findings results in better outcomes. METHODS: Participants had a new syphilis diagnosis, serum RPR titer ≥ 1:32 or peripheral blood CD4+ T cells ≤ 350/ul (in persons living with HIV) and did not endorse neurological symptoms. They underwent computerized cognitive assessment with the CogState. Thirty-two were randomized to either undergo lumbar puncture (LP) or to not undergo LP and 14 underwent LP; 64 were not randomized and 48 opted to undergo LP. RESULTS: Demographics, cognitive complaints and cognitive impairment did not differ between randomized and nonrandomized participants. Two-thirds were cognitively impaired, and impairment was not more common in those with cognitive complaints. The adjusted odds of increased severity of impairment were 3.8 times greater in those with CSF pleocytosis compared to those without. Time to cognitive normalization, improvement or decline did not differ between those who did not undergo LP and those who underwent LP and whose treatment was based on CSF analysis. Taking into account pre-treatment cognitive impairment, the risk of cognitive decline was lower in those with CSF pleocytosis treated for neurosyphilis compared to those without CSF pleocytosis not treated for neurosyphilis, (HR 0.24 (95% CI 0.07-0.88], p = 0.03). CONCLUSION: In individuals at high risk for laboratory-defined neurosyphilis, cognitive complaints are not a good indicator of cognitive impairment. Severity of cognitive impairment was greater in those with CSF pleocytosis. Identification and treatment of those with neurosyphilis may mitigate subsequent cognitive decline.

Analysis of EEG Lemple-Ziv complexity and correlative aspects before and after treatment of anti-syphilis therapy for neurosyphilis.

Objective To investigate the diagnostic value of electroencephalogram (EEG) complexity in patients with neurosyphilis by comparing the changes of electroencephalogram Lempel-Ziv complexity (EEG-LZC) before and after anti-syphilis treatment. Methods The EEG complexity of neurosyphilis patients diagnosed in our hospital from July in 2015 to June in 2017 was analyzed and compared with other diagnostic results such as serology examination and cerebrospinal fluid examination. Results A total of 27 patients were diagnosed, including 19 males and 8 females, of which 6 were mesenchymal(cerebrospinal membrane and meningeal vascular), 16 were parenchymal(paralytic dementia, spinal cord tuberculosis and optic neuropathy), and 5 were asymptomatic. After intensive anti-syphilis therapy, the LZC increased significantly in all patients while the trend and degree of change were consistent with other diagnostic results. Conclusion The LZC can be used as one of the diagnostic indexes meanwhile the trend and degree of its change can be used as the reference index of curative effect to neurosyphilis.

Neurosyphilis presenting as cranial nerve palsy, an entity which is easy to miss.

Neurosyphilis is a rare disease that until the 2000s was almost eradicated due to population awareness of HIV and efficient treatment. Since then, the prevalence of the entity is rising due to risk-associated behaviour such as unprotected intercourse. Neurosyphilis is still a difficult entity to diagnose especially when combined with acute HIV infection which can influence the usual clinical course of disease. In rare occasions, both acute HIV and early syphilis infection can present as mono or multiple cranial nerve palsies. This case demonstrates a rare manifestation of misdiagnosed early syphilis infection combined with acute HIV infection in a 34-year-old man with prior history of unprotected sex with men.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Electroclinical and radiological observation of dysfunctional zones in a patient with neurosyphilis.

We report a 33-year-old Japanese man who suffered from repetitive generalized tonic-clonic seizures which were medically intractable. Neurosyphilis was serologically diagnosed in blood and cerebrospinal fluid, and penicillin G (PcG) was consequently effective. The EEG during PcG pre-treatment showed frequent right occipital spikes and right frontocentral slow waves, which disappeared after treatment. During pre-treatment, positron emission tomography with 18-fluorodeoxyglucose and Tc-99m ethyl cysteinate dimer single-photon emission computed tomography revealed occipital hypermetabolism and hyperperfusion ("hot" area) and fronto-temporo-parietal hypometabolism and hypoperfusion ("cool" area) over the right hemisphere. The spike sources of magnetoencephalography during pre-treatment were localized to "hot" areas, and the slow activities were distributed to the fronto-temporo-parietal region, corresponding to "cool" areas. The inflammatory seizure focus and reversible dysfunctional zone associated with neurosyphilis were clearly delineated using these techniques.

[Four-year follow-up of a neurosyphilis case presenting psychiatric symptoms]. / Pszichiátriai tünetekkel jelentkezo neuroszifilisz négyéves utánkövetése.

The authors present a case of neurosyphilis associated with predominant psychiatric symptoms. The elderly man was admitted because of confused behavior, maniform state, lack of critical judgement and grandiose delusions. On admission, right central facial nerve paresis, hand tremor and parkinsonism were also found. Acute brain imaging and routine laboratory tests failed to identify a firm etiology of the confusional state. The psychiatric treatment resulted in complete recovery from delirium. Afterwards, maniform psychosis dominated the clinical picture for which antipsychotics were administered. Later, rapid cognitive deterioration and progression of motor symptoms were observed. MRI revealed cortical and hippocampal atrophy and white matter hyperintensities. Lumbar puncture found pleocytosis and elevated cerebrospinal fluid protein levels. Neurosyphilis had been confirmed by serologic tests. The cognitive symptoms improved and the psychiatric symptoms remitted under penicillin treatment. Four years after diagnosis, there is a gradual progression in the cognitive decline. Two additional hospitalizations were necessary due to the relapses of psychiatric symptoms. Orv Hetil. 2018; 159(6): 234-238.

Diversity in clinical manifestations and imaging features of neurosyphilis: obstacles to the diagnosis and treatment (report of three cases).

OBJECTIVE: To explore the clinical manifestations and imaging features of neurosyphilis and to discuss the obstacles in the diagnosis and treatment of neurosyphilis. METHODS: We present this case study involving three cases of definite neurosyphilis, focusing on their clinical data. RESULTS: Case 1 is a patient with numb and weak left lower limb. Case 2 showed slow reaction and dementia behaviors including worse memory and the decrease of calculation and orientation ability in this patient. Case 3 is a peripheral incomplete left oculomotor nerve palsy patient. Magnetic resonance imaging findings of three patients are different. And single photon emission computed tomography showed the regional cerebral blood flow was all hypoperfused. There were some difficulties in diagnosing and treating the patients in these three cases. CONCLUSION: The clinical manifestations and imaging findings of neurosyphilis are diverse. Clinicians should pay attention to neurosyphilis. After clear diagnosis, patients would receive norm treatment in time.

Orofacial Involuntary Movements in Neurosyphilis: Beyond the Candy Sign.

BACKGROUND: Involvement of the central nervous system in patients with syphilis (neurosyphilis) may result in several neuropsychiatric symptoms. Rarely, patients with neurosyphillis may develop movement disorders with different phenomenology. Subtle orofacial dyskinesias have been reported in patients with neurosyphilis, known as the candy sign. CASE REPORT: We describe a patient with neurosyphilis who presented with severe orofacial involuntary movements. DISCUSSION: Our patient had orofacial movements at presentation and severity of the movements was much higher than the candy sign that has been reported in patients with neurosyphilis. This report contributes towards the ever-expanding clinical spectrum of neurosyphilis.

Early neurosyphilis presenting with facial palsy and an oral ulcer in a patient who is human immunodeficiency virus positive: a case report.

BACKGROUND: Neurosyphilis is the tertiary stage of Treponema pallidum infection that involves the central nervous system, which occurs within days or weeks after an initial syphilis infection, especially in immunocompromised patients. The diagnosis of neurosyphilis is quite challenging as it is uncommon and often presents with obscure symptoms since any organ system may be involved. CASE PRESENTATION: We describe a case of a 40-year-old African man who is human immunodeficiency virus positive with early neurosyphilis who presented with a stiff neck, headache, confusion, restlessness, and a left-sided chest pain; he did not respond to an empiric treatment of ceftriaxone and fluconazole for meningitis, and tramadol for headache. Ten days after admission, he developed generalized tonic-clonic convulsions; on examination he had ipsilateral facial nerve palsy and an oral ulcer, and responded well to benzathine penicillin treatment. CONCLUSIONS: Laboratory diagnosis of neurosyphilis is challenging because to date there is no single laboratory test which is considered sensitive enough for diagnosis of the disease, especially in resource-limited settings. Clinical judgment is still an important part of diagnosis; and neurosyphilis should be considered a diagnostic differential in patients with Human Immunodeficiency Virus presenting with central nervous system involvement and in other high-risk patients.

Clinical and Biological Characteristics of 40 Patients With Neurosyphilis and Evaluation of Treponema pallidum Nested Polymerase Chain Reaction in Cerebrospinal Fluid Samples.

BACKGROUND: Syphilis remains a significant public health problem. We conducted a prospective study to define more precisely the clinical and biological characteristics of patients with neurosyphilis (NS), and we assessed the diagnostic value of nested polymerase chain reaction (PCR) testing for Treponema pallidum in cerebrospinal fluid (CSF) samples. METHODS: From 2001 to 2013, we included 40 patients (90% men; 45% infected with human immunodeficiency virus) with NS, defined as syphilis with neurological and/or ophthalmological symptoms and CSF abnormalities. RESULTS: Thirty patients (75%) had early, 5 (12.5%) had late, and 5 had meningovascular NS. Twenty-four patients (80%) with early NS had ophthalmological symptoms, 14 (47%) had neurological symptoms, and 8 (26%) had both. All patients with meningovascular NS had only neurological symptoms. All patients with late NS had neurological symptoms, and 2 (40%) also had ocular symptoms. Ophthalmological symptoms were present in 65% of all patients with NS, and neurological symptoms in 60%. Seventeen patients (42.5%) had CSF white blood cell counts >20/µL (mean, 57/µL), and 27 (67.5%) had high CSF protein levels (>0.5 g/L; mean value, 1 g/L). CSF PCR results were positive in 42%, and CSF VDRL results in 30%. The nested PCR assay had an overall sensitivity of 42.5%, a specificity of 97%, a positive predictive value of 77%, and a negative predictive value of 86%. CONCLUSIONS: Early NS is the most frequent presentation, with an overrepresentation of polymorphous ophthalmological symptoms. PCR is highly specific and of potential value when used with other biological parameters.

Don't Forget What You Can't See: A Case of Ocular Syphilis.

This case describes an emergency department (ED) presentation of ocular syphilis in a human immunodeficiency virus (HIV) infected patient. This is an unusual presentation of syphilis and one that emergency physicians should be aware of. The prevalence of syphilis has reached epidemic proportions since 2001 with occurrences primarily among men who have sex with men (MSM). This is a case of a 24-year-old male who presented to our ED with bilateral painless vision loss. The patient's history and ED workup were notable for MSM, positive rapid plasmin reagin (RPR) and HIV tests and fundus exam consistent with ocular syphilis, specifically uveitis. Ocular manifestations of syphilis can present at any stage of syphilis. The 2010 Centers for Disease Control and Prevention guidelines now recommend that ocular syphilis be treated as neurosyphilis regardless of the lumbar puncture results. There is a paucity of emergency medicine literature on ocular syphilis. For emergency physicians it is important to be aware of iritis, uveitis, or chorioretinitis as ocular manifestations of neurosyphilis especially in this high-risk population and to obtain RPR and HIV tests in the ED to facilitate early diagnosis, and treatment and to prevent irreversible vision loss.

Neurosyphilis as a great imitator: a case report.

BACKGROUND: Neurosyphilis is defined as any involvement of the central nervous system by the bacterium Treponema pallidum. Movement disorders as manifestations of syphilis have been reported quite rarely. CASE PRESENTATION: We report a case of a 42-year-old Russian man living in Estonia with rapidly progressive dementia and movement disorders manifesting as myoclonus, cerebellar ataxia and parkinsonism. The mini mental state examination score was 12/30. After excluding different neurodegenerative causes, further diagnostic testing was consistent with neurosyphilis. Treatment with penicillin was started and 6 months later his mini mental state examination score was 25/30 and he had no myoclonus, parkinsonism or cerebellar dysfunction. CONCLUSION: Since syphilis is easily diagnosed and treatable, it should be considered and tested in patients with cognitive impairment and movement disorders.

Clinical and neuropsychological characteristics of general paresis misdiagnosed as primary psychiatric disease.

BACKGROUND: Neurosyphilis is caused by the invasion of Treponema pallidum into the central nervous system. General paresis (GP) is a type of neurosyphilis. The main manifestation of general paresis is dementia; however, this is different from the other types of dementia, which can be cured by adequate doses of penicillin in the early stage. Neurosyphilis is the "great imitator" because it can mimic many types of medical disorders. In addition, the manifestations of neurosyphilis are not typical. Psychiatric disorders as a cause of general paresis have become more common due to the use of antibiotics. Patients with a psychiatric manifestation are often misdiagnosed. The purpose of this study was to explore the differences in the clinical and neuropsychological characteristics of general paresis between patients misdiagnosed as having a primary psychiatric disease and patients diagnosed correctly upon seeing a doctor. The results may assist clinicians in the early identification of neurosyphilis with a mental disorder. METHOD: The demographic and clinical manifestations, laboratory tests, and neuroimaging and neuropsychological characteristics were analysed in 55 general paresis patients with psychiatric disorders, including 29 patients misdiagnosed as primary psychiatric disease and 26 patients diagnosed as having general paresis after being seen once by a doctor. RESULT: All of the patients had positive assay results for cerebral spinal fluid (CSF) Treponema pallidum hemagglutination (TPHA). Only 43.3 % of misdiagnosed patients and 30.8 % of general paresis patients had positive results for the CSF rapid plasma reagin (RPR) test; 96.4 % patients had abnormal neuroimaging. Mood disturbances were the most common psychiatric disorder in the general paresis patients, especially agitation, between the two groups (patients with general paresis who were misdiagnosed as having primary psychiatric disease and patients who had never been misdiagnosed) (p = 0.011). CONCLUSION: Our findings reinforce the importance of performing serologic testing for syphilis. This should be a part of the evaluation of patients with psychiatric disorders, especially patients with cognitive impairment. When the syphilis serology is positive, the patient should be examined thoroughly for neurosyphilis by lumbar puncture. Brain imaging could also aid the physician in discriminating these patients from those with a functional mental disorder.