Although psychiatric symptoms are rarely encountered as the sole clinical manifestation of neurosyphilis nowadays, this case emphasizes that neurosyphilis should be considered as a potential differential diagnosis of neuropsychiatric syndromes in current psychiatric practice, even in HIV seronegative patients. Mitsonis et al. [6] reviewed the medical records of 81 hospitalized patients with neurosyphilis, from 1965 to 2005. During the period 1965–1984, only 27.4% of the patients with neurosyphilis exhibited psychiatric manifestations, whereas nearly 86% exhibited psychiatric symptoms during the period 1985–2005. In a previous retrospective review of neurosyphilis [5], the most common symptoms were personality change and memory impairment. Neurological abnormalities were also common, especially the absence of pupillary reaction to light and buccolingual masticatory movements. On the other hand, neurosyphilis presenting as paranoia, delusional thinking, and mood disorder has also been reported [7, 8]. Specific forms of hallucinations or schizophrenia-like symptoms as well as depressive and manic episodes were observed in patients with neurosyphilis [1, 8, 9]. Although there are no pathognomonic brain imaging findings that suggest neurosyphilis [4], several abnormal MRI findings, including generalized cerebral atrophy and foci of increased signal intensity on T2-weighted images, have been reported [10].
Interestingly, in the present case, prominent symptoms of psychotic mania were presented without any abnormalities in cognition, results of neurological examination, or brain MRI. Even though neurosyphilis may present with virtually any psychiatric symptom [1, 11], there has been only one case report of neurosyphilis presenting psychotic mania without any cognitive or neurological abnormalities [12]. Despite the patient fulfilling the diagnostic criteria for psychotic mania, some features of the case implied an organic cause of his manic-like episode with psychotic symptoms. Firstly, compared with over half the bipolar disorder patients having at least one family member with mood disorder [13], this case did not have any family history of psychiatric illness. Secondly, the patient showed the first manic-like episode in his late 40s, which is in contrast with the mean onset age of 30 years for bipolar disorder [14]. Moreover, given that patients with bipolar disorder typically show marked distractibility or hyperactivity during a manic episode, unimpaired cognition, particularly concentration, and absence of severe hyperactivity suggest an atypical feature of bipolar disorder, which emphasize the need to consider another disease as a differential diagnosis.
Penicillin has been considered as the treatment of choice for neurosyphilis [4]. The recommended regimen for neurosyphilis is 18–24 million units of intravenous aqueous penicillin G daily, either a continuous infusion or divided every 4 h, for 10–14 days [15]. In this case, the patient was administered blonanserin in addition to intravenous penicillin G, and after a few days, his psychiatric symptoms improved dramatically. To our knowledge, there has been no report as to the efficacy of blonanserin in the treatment of neurosyphilis. Blonanserin is a novel atypical antipsychotic drug which was approved for treatment of schizophrenia within the dose range of 8–24 mg/day in Japan and Korea [16, 17]. It has been shown to have potent antagonistic properties at dopamine D2 and serotonin 5-HT2A receptors, and is effective in alleviating positive and negative symptoms of schizophrenia [18, 19]. Although there are no specific guidelines to address psychiatric symptomatology, previous case series reported neurosyphilis-related psychotic symptoms to be treated successfully with typical or atypical antipsychotic drugs, concurrent with penicillin therapy [20]. The authors recommend that the lowest effective doses of antipsychotic agents could be utilized in severe cases requiring admission. Also, periodic attempts to reduce or withdraw these agents should be considered to minimize adverse events. Considering the rapid amelioration of psychotic mania-like symptoms, combination of blonanserin with penicillin may be more effective than penicillin monotherapy, suggesting a potential role of antipsychotic drugs in the treatment of psychiatric symptoms accompanied by neurosyphilis. Further, prognosis of the patient would be relatively good based on excellent treatment response, unimpaired cognition, and lack of neurological abnormalities.
This case report has several limitations. Although the possibility is thought to be low, it cannot be ruled out that the syphilis infection may have been caused by unrecognized manic symptoms of preexisting bipolar disorder. Moreover, given that the patient had experienced visual hallucinations, the MMSE may be insufficient for evaluation of cognitive function.
In conclusion, neurosyphilis remains a challenge in the field of clinical psychiatry because of its pleomorphic psychiatric symptomatology. Nevertheless, neurosyphilis is a treatable medical condition if it is accurately diagnosed early. The present case illustrates the difficulty in diagnosing neurosyphilis due to psychotic mania-like symptoms being the sole clinical manifestation. Thus, psychiatrists should keep in mind the need for a high index of suspicion and comprehensive laboratory work-up for possible syphilis when patients present with an abrupt onset of atypical psychiatric manifestation, especially in the absence of personal or family history of psychiatric illness. Also, this case suggests that combination of a low dose of blonanserin with antibiotic therapy may be an effective treatment option for psychotic mania-like symptoms associated with neurosyphilis.
