64Cu-DOTATATE-PET Imaging for Lyme Neuroborreliosis

Background

Imaging of neuroinfections is well documented, however with several restrictions due to the heterogeneity of pathogens. Lyme neuroborreliosis (LNB) is a tick-borne infection, caused by Borrelia burgdorferi sensu lato complex (Bb) and among the most prevalent bacterial infections of the nervous system. Due to climatic and environmental changes, the incidence of tickborne diseases is increasing throughout Europe, in Denmark the annual incidence is estimated to 3-4/100,000. Adults mainly manifests as a self-limiting subacute painful meningoradiculitis, lymphocytic meningitis and/or cranial nerve palsy, symptoms of CNS involvement such as acute encephalitis and myelitis are rare. Over time, most cases of Bb infection is thought to be self-resolving, however antibiotics accelerate the process by eradicating the pathogen and reduces the risk of disseminated late infection and persistent symptoms. The response to antibiotics can be slow, but the majority of patients report marked improvement in symptoms after treatment, a proportion of patients, do however report to experience persistent residual symptoms including fatigue, pain or cognitive disturbances and studies have suggested that late diagnosis and the burden of symptoms at time of treatment initiation increases the risk of these symptoms.

If antibiotic treatment is initiated as early as possible, LNB has a very good prognosis, early diagnosis and treatment initiation are therefore of paramount interest.

As no markers in plasma can be used to diagnose or follow LNB, the diagnosis of LNB is based on clinical symptoms in combination with elevated white blood cell count in cerebrospinal fluid (CSF) and the detection of specific Bb intrathecal antibody production. However, Bb serology has several disadvantages in the ability to confirm active disease and monitor disease activity and response to antibiotic treatment. Bb antibodies in CSF are first detectable weeks after onset of the neuroinfection and they may persist for years even after the disease has been well-treated. In addition, symptoms can be unspecific, evolving over time and even mimic other neurological diseases potentially resulting in misdiagnosis, diagnostic delay and reduced patient outcome. The investigators recently reported a median duration of neurological symptoms before first hospital contact of 21 days in a Danish nationwide prospective cohort study of 194 LNB patients included between 2015-2018. Currently, the only way to monitor disease activity - although not ideal - is to to perform a re-lumbar puncture, which is an invasive procedure, not always possible or successful and with risk of post lumbar puncture headache which develops in 10-20% of the patients.

Improving diagnosis, ideally non-invasively, is therefore of great interest and new methods to confirm active disease and monitor the effect of treatment an important field of research which might promote a shift from empirical treatment to personalized medicine with expected improvement in patient outcome.