Schizophrenia-like psychosis as the presenting feature of neurosyphilis in a non-human immunodeficiency virus-infected Indian man: A reminder of a forgotten complication!

Syphilis is a great masquerader of several diseases. About 4%-10% of patients with untreated syphilis may develop neurosyphilis (NS). Psychiatric manifestations may rarely be the presenting feature of NS. We describe herein a case of an elderly man who presented with psychosis and after thorough workup was diagnosed to be a case of a NS. Schizophrenia-like psychosis as the presenting and the only manifested feature of NS in a nonhuman immunodeficiency virus-infected patient was a unusual and noteworthy feature in the present case.

INTRODUCTION

Syphilis, a great imitator of several diseases, has significant associations to neuropsychiatry for years.[1] Approximately 4%–10% of patients with untreated syphilis may develop neurosyphilis (NS).[2] It is generally considered to be a late manifestation of syphilis. However, some degree of acute or subacute septic meningitis is present even in primary syphilis. Therefore, in the broader sense, it begins early and may be present in any stage of syphilis.[3] The clinical presentation of NS seems to have largely changed in the recent era. An increasing number of cases have been reported in immunocompetent and heterosexual patients. In human immunodeficiency virus (HIV) patients, NS usually follows a more fulminant course. However, in immunocompetent individuals, the disease may remain asymptomatic or is more insidious, with nonspecific symptoms leading to underdiagnosis of this condition.[2] Several psychiatric and neurological manifestations take place in the setting of NS. We present here a patient with NS in a non-HIV infected patient in whom schizophrenia-like psychosis was the presenting and the sole manifested feature. The case is reported for its unusual and interesting clinical features.

CASE REPORT

A 44-year-old Hindu man, father of two children, was brought to us with a history of gradual onset of suspiciousness and aggressive behavior for the preceding 4 months. His symptoms were progressive in nature. He had a strong belief that his neighbors were planning to kill him and were closely watching his every movement.

He also had suspicion that his family members were also involved in the conspiracy. He used to hear a single male voice, which he could not see, and that was derogatory in nature (e.g., “you are finished,” “I will see you,” etc.). His family members also complained that the patient habitually used abusive languages to them and neighbors since starting of the disease, and often became violent and destructive. Frequently, the patient used to engage in fighting with other people even with a slightest provocation or sometimes without a valid ground. His sleep was very much disturbed. He almost remained awake since starting of the symptoms and was not interested to take food, daily bath, or to maintain his personal cleanliness. Moreover, he was gradually becoming absentminded, forgetful, and unable to handle money and/or business properly. He was married 10 years ago. Before marriage, he used to drink alcohol irregularly. The patient denied any history of high-risk sexual behavior. There was no history of head injury, convulsion, or any past or family history of psychiatric illness. Mental status examination (MSE) revealed a fairly well-kempt man who had poor eye contact and increased psychomotor activity. His speech was relevant, adequate but loud. He had second person auditory hallucination, delusion of persecution, delusion of reference, and poor insight and judgments.

He had poor attention, concentration, and recent memory. Systemic examination including detailed neurological examination was noncontributory except mild exaggeration of deep tendon reflexes. On the basis of history and MSE, he was diagnosed a case of schizophreniform disorder. He was put on risperidone 4 mg, trihexyphenidyl 2 mg, and clonazepam 1 mg and was improved a lot within 2 weeks of treatment. About 2 months later, he developed florid psychotic features due to drug discontinuation. We again started the same medicines.

At that time, he did not responded well rather he developed severe extrapyramidal symptoms (EPS). Subsequently, risperidone was replaced by olanzapine 10 mg/day. However, his EPS was not improving, and the forgetfulness was increasing day by day. At that time, we admitted him for thorough examination and investigation. On admission, his Mini–Mental State Examination (MMSE) score was 17/30, and score on Addenbrooke's Cognitive Examination-Revised was 44/100. Routine investigation including complete hemogram, sugar, urea, creatinine, sodium, potassium, liver function test, chest X-ray, and electrocardiography was within normal limits. Thyroid profile, Vitamin B12, and folic acid were also within the normal range. His magnetic resonance imaging (MRI) showed cerebral and cerebellar atrophy with small subacute infarct in the right putaminal and periventricular region and lacunar infarcts in the periventricular region [Figure 1]. Blood for HIV was negative, but serum venereal disease research laboratory test (VDRL) came to be positive in 1:16 titer. Subsequent TPHA examination was also positive. Cerebrospinal fluid (CSF) study showed high leukocytes count (40/cmm, all lymphocytes), low glucose (21 mg/100 ml), and high protein content (159 mg/100 ml). Gram stain and Ziehl–Neelsen stain were noncontributory. Cerebrospinal fluid VDRL test was reactive. On the basis of the clinical findings, imaging, and laboratory investigations, a diagnosis of NS presenting with schizophrenia-like psychosis was made.

Figure 1

(a and b) Magnetic resonance imaging showing cerebral and cerebellar atrophy with small subacute infarct in the right putaminal and periventricular region and lacunar infarcts in the periventricular region

We treated him with intravenous (IV) injections of 1 g of ceftriaxone once daily (after proper skin sensitivity test) for 2 weeks along with tablet olanzapine 7.5 mg and tapering doses of clonazepam. The patient showed signs of gradual improvement. After 6 weeks of treatment, his psychotic symptoms almost disappeared, and at that time, his MMSE score increased to 26/30, suggestive of significant improvement.

However, his extrapyramidal symptoms showed partial improvement. The VDRL test (blood) was nonreactive at this point. Later, with high confidentiality, he admitted that he had exposure with commercial sex workers before marriage.

DISCUSSION

NS may present with a wide gamut of symptoms and signs. However, a subset of patients may remain asymptomatic. Based on the dominant clinical manifestations, NS has three patient group classifications, namely neuropsychiatric, meningovascular, and myelopathic groups.[4] Early NS usually affects mesodermal structures (i.e., mainly meninges and vessels), whereas late NS affects the brain and spinal cord parenchyma. These syndromes may overlap, leading to combined forms.

Neurological symptoms of it may include ataxia, stroke, urinary incontinence, ophthalmic symptoms, lightning pain, dizziness, headache, hearing loss, and seizures. Clinical examination reveals several combinations of neurological signs including hyporeflexia, sensory impairment (e.g., decreased proprioception, loss of vibratory sense, otosclerosis, vertigo, sensory ataxia, chorioretinitis), pupillary changes (e.g., anisocoria and Argyll Robertson pupils), cranial neuropathy, positive Romberg sign, Charcot joint, hypotonia, and optic atrophy among others.[35]

On the other hand, a wide range of psychiatric manifestations may be present in NS. The occurrence of psychiatric signs and symptoms associated with NS reported in the literature ranges from 33% to 86%.

The most common (48%) presenting neuropsychological symptoms comprise personality change and hallucinations.[6] A significant number of patients with NS may have dementia, especially with temporoparietal lobe involvement. Mood symptoms including both depressive and/or manic features may be present.

Another manifestation of NS is psychosis, which may often be indistinguishable from psychotic features of schizophrenia. Schizophrenia-like psychosis as the presenting and the sole manifestation was a noteworthy feature in the present patient.

Patients may have altered personality, substance-related features, and sexual dysfunction. It is noteworthy that NS must be kept in the differential diagnosis of delirium when all other possible causes are excluded from the study.[7]

A reactive serologic test for syphilis and reactive VDRL in CSF confirms the diagnosis of NS.[389] Although VDRL-CSF is highly specific, it may be negative in up to 50% of samples from patients with NS.[9] Therefore, a negative VDRL-CSF result does not essentially rule out the diagnosis of NS.[9] In a patient with syphilis of any stage with a negative VDRL in CSF having clinical symptoms or signs consistent with NS without other known causes for these clinical abnormalities and elevated CSF protein or leukocyte count in the absence of other known causes of these abnormalities, the diagnosis of NS is probable.[8]

MRI findings of a patient with NS may show diffuse cerebral atrophy, parenchymal signal changes in the mesial temporal region and temporal and basifrontal regions, infarcts, and nonspecific white matter changes. Patients with meningovascular form showed infarcts, diffuse cerebral atrophy, signal changes in the mesial temporal region, sulcal exudates, progressive multifocal leukoencephalopathy, and a mass surrounding the carotid sheath. In consonance with the existing literature, MRI of our patient showed cerebral and cerebellar atrophy with small subacute infarct in the right putaminal and periventricular region and lacunar infarcts in the periventricular region. Spine imaging may reveal long-segment signal changes, contrast enhancement, and dorsal column involvement. However, imaging should be interpreted with caution as normal MRI is also commonly found in those cases.[4]

The first-line treatment options for NS is IV injection of aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4 h or continuous infusion, for 10–14 days. The alternative regimen might include injection Procaine penicillin G 2.4 million units IM once daily plus probenecid 500 mg orally four times a day, both for 10–14 days.[3]

Studies showed that IV ceftriaxone may be a reasonable alternative to penicillin for treatment of HIV-1-infected patients with NS and concomitant early syphilis.[10] In our patient, we have advised IV injection of ceftriaxone due to local unavailability of penicillin at that point of time.

CONCLUSION

Psychiatric symptoms are often overlooked as presenting features of NS. Clinicians may often fail to include syphilis in the differential diagnosis for psychiatric disorder.

In this article, we sought to emphasize that high degree of suspicion and relevant focused investigations are the key factors for the early diagnosis and hence appropriate treatment of such patients. In our case, there were neither any dermatological manifestations nor any other features of tertiary syphilis. Serological testing for HIV-I and HIV-II was also negative. Patients with early NS may respond better to therapy than those with a late presentation of the disease; thus, early diagnosis remains important for a good clinical outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.