In the early 20th century, new-onset psychosis secondary to neurosyphilis was common. With the advent of antibiotics, cases of neurosyphilis-induced psychosis became rare. A rise occurred in the late 20th century with the rise of HIV coinfection. Today, sexually transmitted infections are increasing in the US. The Centers for Disease Control and Prevention (CDC) stated in August 2018 that diagnoses of syphilis increased 76% from 2013 to 2017,1 which may be understated as many cases are not diagnosed. In a CDC report in 2016, rates of primary and secondary syphilis increased from 2.1 (2000-2001) to 8.7 (2015–2016) cases per 100,000.2

It would not be surprising in this context if neurosyphilis was also increasing. However, the clinical suspicion for neurosyphilis is as low as 36%, delaying diagnosis and treatment by as much as 24 months.3 For clinical neuropsychiatrists, syphilis testing is among the standard laboratory tests obtained during admission or changes in behavior or cognition.

Natural History

Syphilis is treatable and, when treated in the early stages, should not progress to neurosyphilis. With antibiotics, there is less disease progression, which may explain the low clinical suspicion. Neurosyphilis can occur at any stage of infection and take many different forms, from seemingly benign meningitis, to meningovascular disease leading to strokes, to tabes dorsalis, or general paresis. This has earned neurosyphilis the epithet of “the great imitator.” Although more severe manifestations typically occur 10 to 25 years postinfection, psychosis and general paresis can occur as early as 2 years postinfection; in the prepenicillin era, it was described at 8 months postinfection.4

Case Studies

We discuss 2 patients with different presentations in order to discuss testing considerations and to demonstrate the importance of carefully considering syphilis in presentations of cognitive decline, psychosis, and catatonia (Case 1 and Case 2).


Given the history of partial treatment for syphilis, clinical examination findings, and positive CSF VDRL, the patient was treated for neurosyphilis with IV penicillin G. For the catatonia secondary to neurosyphilis, he was continued on lorazepam, started on electroconvulsive therapy 3 times per week, and started on memantine and zolpidem. With treatment, his clinical picture greatly improved. He had improved alertness, responsiveness, speech, reality testing, and ambulation. He was able to play chess (frequently defeating medical students) and make artwork. He continued to have bradykinesia, hypertonicity (improved), left upper extremity flexor posturing with spasticity, hyperreflexia, intention tremor, and distal weakness.


The patient was eventually discharged home with a BFCRS score of 0 and no evidence of psychosis; however, he had residual difficulties with executive function and memory as well as a slowed gait and residual weakness in his left arm. His discharge medications were lorazepam 1 mg twice a day and zolpidem 10 mg at night for sleep. Repeat CSF analysis 6 months after presentation showed an appropriate decline in VDRL titer to 1:8. Repeat outpatient testing was scheduled for another 6 months later.


Both patients had partially treated syphilis and no history of psychotic illness or cognitive disorder. Per collateral reports, the patients did not have a family history of mental illness. Both were outside of the usual age for a first break psychosis. It is now clear that the history of the patient in Case 1 had a gradual progression of suspicious symptoms. It could be argued that the patient in Case 2 may have also showed symptoms prior to the psychosis. The cerebrovascular accident that occurred in his 40s could have been a product of meningovascular complications of neurosyphilis. The diagnoses of hypertension and diabetes, also increasing his risk of stroke, overshadowed consideration of syphilis as an underlying cause.

These cases emphasize the importance of testing for syphilis in new-onset psychotic and cognitive disorders, as well as ensuring complete treatment to prevent further complications and disability. The algorithm for testing varies depending on the institution, starting with either nontreponemal testing followed by treponemal testing or vice versa (Table).5-7 Careful review of a patient's clinical history is required to guide testing and treatment for syphilis.

High suspicion for neurosyphilis led to cerebrospinal fluid (CSF) analysis in both cases, allowing for appropriate diagnosis and treatment. It is notable that the patient in Case 2 had a negative CSF venereal disease research laboratory (VDRL) test. Considering only CSF VDRL, he may not have received treatment specifically for neurosyphilis. With appropriate treatment, both cases showed great clinical improvement. Antipsychotics were no longer needed for the patient in Case 1 and were minimized for the patient in Case 2. Impairments remained that may have had better outcomes if there had been earlier diagnosis and treatment of syphilis.

1. Centers for Disease Control and Prevention. 2018 New CDC analysis shows steep and sustained increases in STDs in recent years. https://www.cdc.gov/nchhstp/newsroom/2018/press-release-2018-std-prevention-conference.html.

2. Centers for Disease Control and Prevention. 2016 Sexually transmitted diseases surveillance. https://www.cdc.gov/std/stats16/syphilis.htm. Accessed December 10, 2018.

3. Zheng D, Zhou D, Zhao Z, et al. The clinical presentation and imaging manifestation of psychosis and dementia in general paresis: a retrospective study of 116 cases. J Neuropsychiatry Clin Neurosci. 2011;23(3):300-307.

4. Cadavid D. Handbook of Clinical Neurology: Bacterial Infections of the Central Nervous System. Philadelphia: Elsevier; 2010.

5. Cantor AG, Pappas M, Daeges M, Nelson HD. Screening for syphilis: updated evidence report and systematic review for the US Preventative Services Task Force. JAMA. 2016;315(21):2328.

6. Hart G. Diagnostic decision: syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med. 1986;104(3):368-376.

7. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1.