A new role of 11C‐Choline PET in localizing the epileptogenic foci in insular cortex in the patients

Abstract

Epilepsy has been acknowledged as a most common severe neuro‐ logical disorder, which affects more than 50 million people world‐ wide.1 The pathogenesis of epilepsy is complicated, ranging from single genetic point mutations to metabolic dysfunction, as well as developmental, neoplastic or acquired brain lesions. Despite appro‐ priate therapy with antiepileptic drugs, up to 30% of patients con‐ tinue to suffer from frequent seizures.2 For these patients, epilepsy surgery must be seriously considered since multiple studies have shown that cure of seizures may be achieved by removing the epilep‐ togenic zone. At present, the most epilepsy surgeries are performed in both temporal (50%‐75%) and frontal lobes (25%). However, these operations cannot completely control the induction of seizures, because insular epilepsy is misdiagnosed with temporal, frontal, or even parietal lobe epilepsy that is unfortunately operated in the wrong area,2 and the fact that a more complex epileptogenic net‐ work includes not only the temporal lobe but also the neighboring insula cannot be recognized comprehensively. The insular cortex, the fifth and smallest lobe of the brain, is a com‐ plex structure enclosed in the depth of the Sylvian fissure covered by the frontal, parietal, and temporal opercula. Due to the difficult ac‐ cess to insular cortex and the high density of blood vessels within the sylvian fissure, the method of electrode implantation has limitations. Moreover, scalp EEG is often misleading, as insular seizures could mimic seizures originating from frontal, temporal, and parietal areas. More recently, in clinical practices, the MRI and positron emission tomography (PET) as noninvasive diagnostic technologies have been widely used to localize the epileptogenic zone for years. However, MRI‐negative cases still account for up to 25% of all patients exposed to presurgical evaluation.3 In addition, the major drawback in clinical PET imaging is lack of specificity: In epilepsy, 18F‐FDG PET shows both the cause and consequence of seizure activity in the focus and projec‐ tion area of the seizure onset. This can make treatment decisions for surgery difficult. Moreover, due to the transient of the ictal state, the way to effectively and timely gather the information on the epilepto‐ genic zone by the technology of PET is inconvenient for the clinicians. So, the development of new specific PET radiotracers to identify focal abnormalities during the interictal state and inform surgical treatment has been a long‐term aspiration in epilepsy surgery. Choline, as an en‐ dogenous substrate, plays the main physiological role in participating into the processes of biochemistry, such as structural integrity and sig‐ naling roles for cell membranes.4 In addition, choline has been widely used as a radiotracer in the diagnosis of primary prostate cancer and low‐grade astroglioma, which suggests that the proliferation of tumor cells, astroglioma in particular, can contribute to the hypermetabolic level of choline. Therefore, based on the theory that neuronal loss or dysplasia always companies with astrogliosis in the epileptogenic zone, and choline can be conducive to synthesis of cell membrane during the process of astrogliosis,5 we selected 11C‐Choline as the new radio‐ tracer for diagnosis of insular epilepsy in the interictal state and further explored its clinical values for providing the new insight into accurately localizing the epileptogenic zone in the present study. We enrolled nine patients who were diagnosed as epilepsy and further suspected of insular epilepsy based on both scalp video‐EEG monitoring data and the typical clinical semiology (Table 1). Those met these following criteria: 1. At least one scalp video‐EEG spike sources were observed (anterior and/or posterior operculoinsular cluster, and/or diffuse perisylvian scatter); 2. All of those had suf‐ fered from at least one of the following symptoms: (a) the conscious‐ ness of patient was not lost completely at the beginning of the attack and could response to the surrounding environment; (b) somatosen‐ sory symptoms, such as the sensation of tingling, warmth, tension, or electrical current, could involve either large cutaneous territories or be restricted to an limited area; (c) visceral movement and vis‐ ceral sensory symptoms were shown, such as nausea, vomiting, the tightness of the throat, and a feeling of pressure behind the sternum and the abdomen, in accompany with a large amount of saliva over‐ secreted and the abnormal heart rhythm; (d) gustatory or auditory hallucinations and postictal aphasia were shown. According to the protocols described in the previous work,6 the high‐resolution MRI brain scans were performed in the nine pa‐ tients with 3.0 T MR scanner (MR 750 Discovery, General Electric Company), including axial three‐dimensional (3D) T1‐weighted se‐ quences (Figure S1A), axial and coronal T2‐weighted sequences (Figure S1B), and axial and coronal fluid‐attenuated inversion re‐ covery (FLAIR, Figure S1C). The results showed that there were a T1 hypointense and T2/FLAIR hyperintense lesion in the left‐side insular cortex in one patient, indicating that tumor might exist, and there was the normal surface area of bilateral insular cortex or the