Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study

Kuriko Kagitani-Shimono,Jun Hatazawa,Ryoko Kuwayama,Shin Nabatame,Haruhiko Kishima,Hiroki Kato,Masako Taniike,Koji Tominaga

doi:10.1186/s12974-020-02055-1

Kuriko Kagitani-Shimono, Jun Hatazawa + Show 6 more

Open Access

https://doi.org/10.1186/s12974-020-02055-1

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Abstract

BackgroundNeuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [11C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy.MethodsPatients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [11C] DPA713. The PET image of [11C] DPA713 was co-registered to individual’s magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed.ResultsTwenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [11C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [11C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [11C] DPA713 uptake. The SUVr of [11C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [11C] DPA713 uptake was associated with microglial activation.ConclusionsThis study indicates that [11C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.

Highlights

Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet
A total of 20 patients underwent interictal FDG-positron emission tomography (PET), and 15 (75.0%) patients showed focal hypometabolism. [11C] DPA713PET, which was performed during the interictal period, was positive in the epileptogenic zone in 23 (85.1%) patients (Table 2)
In this study, we found that (1) neuroinflammation defined as translocator protein (TSPO) PET positivity was recognized in various child-onset foal epilepsies, including epileptic showed high intensity in the left frontal and right parietal cortex on FLAIR-magnetic resonance imaging (MRI), suggesting cortical tubers

Summary

Introduction

Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. A common chronic neurological disease, affects approximately 65 million people worldwide [1] and is the third contributor to the global burden in neurological disorders [2]. Etiologies, such as genetic structural abnormality, infection, metabolic abnormality, and autoimmune encephalitis [3], have been recognized, while the common pathophysiological mechanisms include (1) increased excitatory neurotransmission and/or reduced inhibitory neurotransmission at the epileptogenic zone and (2) recurrent seizures that may lead to further epileptogenesis or progression of epilepsy. In the last two decades, many new antiepileptic drugs have been developed; approximately 30% of patients still have refractory prognosis [4]. Because neuroinflammation plays an important role in epilepsy and other neurodegenerative disorders, specific in vivo markers for neuroinflammation are needed for therapeutic purposes

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