Meningovascular and parenchymal neurosyphilis showing more extensive inflammatory lesions on ¹⁸F-THK5351 PET than MRI

Abstract

This manuscript complements the clinical course of the first case of neurosyphilis in our previous report (Kotani. et al. Clin Nuc Med 2024) which highlighted the utility of ¹⁸F-THK5351 positron emission tomography (PET), a marker of astrogliosis, to visualize neuroinflammation. The patient was a right-handed man in his early 60s who presented with a three-month history of forgetfulness and subsequent right hemiparesis. Neurological and neuropsychological examinations revealed the right pyramidal signs and impairments in attention, memory, executive function, visuospatial cognition, and verbal fluency. The patient was diagnosed with neurosyphilis based on positive tests for syphilis antibodies in the serum and cerebrospinal fluid (CSF) and elevated CSF cell and protein levels. MRI revealed multiple infarcted lesions that explained the pyramidal signs; however, the lesions responsible for cognitive impairment were not visualized. Two months after penicillin G treatment, the patient exhibited partial improvements in cognitive function, without obvious changes in MRI. To investigate the underlying neuroinflammation associated with astrogliosis, we performed PET imaging after treatment. ¹⁸F-THK5351 PET revealed increased uptake and ¹⁸F-fluorodeoxyglucose (FDG) PET showed decreased uptake in the left deep frontal white matter and thalamus. We believed that the right pyramidal signs were associated with infarctions contributed by meningovascular syphilis in addition to the arteriosclerosis, whereas cognitive impairment was associated with neuroinflammation due to parenchymal syphilis. Furthermore, the impairment of thalamocortical circuits may have compromised the widespread cortical excitability underlying cognitive impairments. This report highlights the utility of ¹⁸F-THK5351 PET imaging in understanding the pathogenesis of neurosyphilis, including cognitive impairment. Further longitudinal studies are required to elucidate the relationship between neuroinflammation and the clinical presentation of neurosyphilis.