Neurosyphilis is defined as any infection of the central nervous system (CNS) by the bacterium T. pallidum. The annual incidence of neurosyphilis varies from 0.16 to 2.1 per 100,000 population (Sabre et al. 2016). Neurosyphilis is divided into four major categories: asymptomatic, meningovascular, parenchymatous, and gummatous (Dourmishev and Dourmishev 2005). Neurosyphilis develops by invasion of the pathogen into cerebrospinal fluid (Hagiya et al. 2015). T. pallidum invades the CNS early in the course of infection. Most patients clear the CNS infection spontaneously; however, those who do not clear the infection are at risk of progressing to neurosyphilis (Brown and Gray 2008).
Meningovascular neurosyphilis develops several years after T. pallidum infection. It typically manifests as meningism, intracranial hypertension, and cerebral infarction. Patients often have restlessness, emotional instability, personality changes, and other neuropsychiatric symptoms (Dourmishev and Dourmishev 2005). The most frequent clinical presentation of meningovascular syphilis is stroke (Feng et al. 2009), but in this case, there were no episodes of stroke. Histologically, the inflammation is mononuclear, specifically lymphoplasmacytic, as in the present case (Feng et al. 2009). Neurosyphilis also causes Heubner arteritis, which is characterized by thickening and lymphocytic infiltration of the intima, which can induce a stroke syndrome (Brown and Gray 2008; Sakai et al. 2014). However, there was no evidence of Heubner arteritis in the present case.
In 1985, meningovascular syphilis was reported to be the most common clinical variety of neurosyphilis, comprising 39 to 61% of all symptomatic neurosyphilis cases (Burke and Schaberg 1985). But in 2005, meningovascular syphilis was observed in only 10 to 35% of all neurosyphilis cases, occurring between 4 and 10 years after initial infection, with peak occurrence at 7 years (Dourmishev and Dourmishev 2005).
The widespread use of antibiotics in recent years, particularly penicillin, has considerably modified the forms and stages of syphilis and, subsequently, the clinical features of neurosyphilis (Nyatsanza and Tipple 2016). Symptoms once considered typical, such as those of the eyes (particularly the characteristic Argyll-Robertson pupil), VIII cranial nerves, and tabes dorsalis, have diminished significantly in recent years. Mental disorders and cognitive impairment are now the most common clinical manifestations of neurosyphilis (occurring in 85.7 and 64.3% of cases, respectively) (Yao et al. 2012; Ghanem 2010).
Although immunohistochemical staining of brain tissue sections was negative for T. pallidum, the real-time PCR assay detected low copy numbers. We concluded that the pathogens were most probably present in the brain parenchyma. However, we cannot completely rule out the possibility that the real-time PCR assay detected pathogens contained in a trace amount of blood remaining in the brain tissue samples.
The thromboemboli seen in the autopsy were fresh and were likely to have formed after physical restraints were implemented 4 days before death. The respiratory arrest event that occurred 2 days before death was possibly triggered by the pulmonary embolism. The risk factors for thrombosis in the present case included severe obesity and probable dehydration. In addition, the physical restraints implemented to control neurosyphilis-induced neuropsychiatric symptoms probably contributed to thrombosis. Physical restraint is considered a last resort treatment measure after other non-pharmacological or pharmacological approaches have been exhausted, and is sometimes used in psychiatric clinical practice to manage and treat patients with violent behavior (Cecchi et al. 2012).
Recent studies have reported a resurgence of syphilis worldwide (Hagiya et al. 2015; Centers for disease control and prevention 2016; Golden et al. 2003), which is sometimes discussed in the context of coinfection with HIV (Vaitkus et al. 2010; Feng et al. 2009; Kent and Romanelli 2008). In the USA, the total case count of reported syphilis in 2016 was the highest since 1993 (Centers for disease control and prevention 2016). In Japan, the number of reported syphilis cases continuously decreased from 1948 until 2010, though with slight fluctuations. Since 2010, however, reported cases have been on the rise (National Institute of Infectious Diseases and Tuberculosis and Infectious Diseases Control Division 2015).
In forensic autopsy cases involving neuropsychiatric conditions, forensic pathologists should consider the possibility that the condition was caused by infection of the CNS. Investigation of infectious causes can yield important clues to the immediate cause of death, and to the overall course of events leading to death. Importantly, the cadaver had no skin lesions in this case; we learned from the hospital laboratory that the patient had a syphilis infection. However, we had no information on when or how the patient acquired the infection.
We examined the case focusing on signs of late-stage syphilis. One forensic case of suicide associated with neurosyphilis has been reported (Sakai et al. 2014). The present case highlights the importance of collecting antemortem clinical data for successful autopsy diagnosis and documentation. Further, the likelihood of encountering undiagnosed neurosyphilis should be considered in the future (Sakai et al. 2014).
The diverse presentation of syphilis led William Osler to refer to syphilis as “a great imitator” of other diseases (Nyatsanza and Tipple 2016; Sabre et al. 2016; Dourmishev and Dourmishev 2005). As such, forensic pathologists should pay attention to its myriad of manifestations. This case highlights the need for forensic pathologists to perform a complete autopsy to determine the cause of death in cases of acute thromboembolism with neurosyphilis, including detailed histopathological examination, serological assessment, and genetic testing with PCR techniques, paying attention to the trend of infectious diseases.
