Imaging Inflammation in a Patient with Epilepsy Due to Focal Cortical Dysplasia

Abstract

Background and Purpose Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. PET using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans. We were interested in learning whether [C11]PK11195 PET (PK-PET) can identify areas of focally increased inflammation corresponding to seizure foci of patients with epilepsy. Methods A young woman with intractable epilepsy underwent PK-PET as part of an approved research study. PK-PET results were compared with results from other clinical studies. Results PK-PET revealed an area of focally increased radiotracer uptake in the right frontal lobe corresponding to this patient’s seizure focus as identified by ictal and interictal FDG-PET and a video-EEG. Routine brain MRI was considered normal, though high-resolution studies showed possible subtle dysplasia of the right frontal lobe. The patient underwent a right frontal lobe resection, and pathological evaluation showed focal cortical dysplasia with activated microglia. Conclusions PK-PET can identify neuroinflammation associated with subtle focal dysplasia, and may therefore have a clinical role in guiding epilepsy surgery for patients with difficult-to-localize seizure foci.

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain

“…This, however, does not argue against the possibility that they represent electrographic seizures. Monomorphic focal EEG seizures are not uncommon in patients with different types of epilepsy30, 31, 32 and have also been described in other animal models of acquired epilepsy, such as the perinatal hypoxia model of epilepsy 33, 34. Furthermore, the fact that HVSWs can be suppressed by rapidly acting ASDs such as DZP as shown by Klein et al10 in FVB/N mice and here for NMRI mice would be consistent with a nonconvulsive seizure definition as shown in Table 4.…”

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

“…The presence of peripheral immune cells in the brain tissue, and more recently the activation of the toll-like receptors (TLR) signaling pathway, have been demonstrated (Pernhorst et al, 2013;Zattoni et al, 2011). Studies using positron emission tomography (PET) with the C-PK11195 tracer (specific for activated microglia) confirmed these findings in patients with epilepsy secondary to encephalitis (Banati, 2002;Kumar et al, 2008) or with focal cortical dysplasia (Butler et al, 2013). These findings confirmed that the immune-inflammatory phenomenon is intrinsically linked to epilepsy, regardless of its etiology.…”

A Functional Role for Microglia in Epilepsy

“…They concluded that focal areas of neuroinflammation play an important role in refractory seizures associated with encephalitis, and using this imaging approach highlighted the region for surgical removal, and led to a successful recovery. This approach was used again and resulted in the treatment of another female patient with intractable epilepsy due to focal cortical dysplasia (Butler et al, 2011). One can easily imagine from these case reports how examining the time course of microglia activation over the development and progression of epileptogenesis in patients and animal models can truly shed light on the microglial contribution to pathology.…”