We retrospectively analysed the results of the interictal 18F-FDG PET/CT brain scans of 100 FCD patients. CCD was observed in 23% of FCD patients in this study. This rate is lower than the previously reported prevalence of CCD in patients with ictal epileptic seizures and after stroke [15, 17–19]. In addition, our study demonstrated that the number of lobes involved on PET, structural anomalies on MRI, the lesion location on PET, the |AI| in the posterior frontal and anterior temporal lobes may be predisposing factors for CCD, the presence of CCD may affect the prognosis of FCD patients at 12 months postoperatively, and parietal hypometabolism on PET may indicate a poor prognosis. To the best of our knowledge, this is the first interictal 18F-FDG PET/CT study to investigate the incidence of CCD, identify risk factors for seizure-related CCD, and determine the correlation between CCD and prognosis in patients with FCD confirmed by postoperative pathology.
Our results suggest that the number of lobes involved on PET and the lesion location on PET are related to the appearance of CCD. Previous studies have uncovered possible risk factors associated with the presence of stroke-related CCD, but conflicting results still exist. A recent survey of 108 patients with ischaemic stroke within 6 h of onset found no significant differences in the distribution of supratentorial ischaemic lesions between CCD + and CCD- patients using whole-brain volume perfusion CT (CTP) . Kim et al  hypothesized that the location rather than the extent of a lesion may be the primary determinant for the occurrence of CCD in patients with cerebral infarction. They found that CCD + was significantly higher when infarctions were located in the frontoparietal lobes or the deep middle cerebral artery territory compared to other regions (11/19 vs 1/7, P = 0.048). In this study, a significant difference was found between CCD + and CCD- when a hypometabolic brain region was located in the occipital lobe (P = 0.04). The pathophysiologic distinction may need to be studied further to explain the difference. Kunz et al  found no significant association between CCD + and infarction volume (P = 0.972). Conversely, Jeon et al  demonstrated that the supratentorial ischaemic volume on each CTP map did not differ significantly between CCD + and CCD- groups (P > 0.05), but a correlation analysis of the supratentorial ischaemic volume on each CTP map showed a positive and significant linear correlation (P < 0.05). In our study, the CCD + group had a higher number of hypometabolic regions on PET than the CCD- group (P = 0.00), which can be regarded as equal to the volume of the EON. However, the range of hypometabolic regions on PET is always greater than that in the EON [5, 24]; thus, these results do not imply the real volume of the EON. In the future, we need quantitative methods to calculate the real volume of the EON.
We found that the average |AI| values in the posterior frontal and anterior temporal lobes in the CCD + group were significantly higher than those in the CCD- group, but no correlation of the |AI| between supratentorial regions and the contralateral cerebellum was found in CCD + patients. Jeon et al  found that the supratentorial degree of perfusion reduction and the infratentorial asymmetry index were strongly and significantly (P < 0.05) correlated with each other in CCD + patients. Kunz et al  showed that CCD + patients had larger supratentorial cerebral blood flow deficits than CCD- patients (median: 164 ml vs. 115 ml; P = 0.001) by CT perfusion imaging among acute ischaemic stroke patients. To date, most studies on CCD have focused on cerebral perfusion, and studies on cerebral metabolism are lacking. Cerebral blood flow perfusion and cerebral glucose metabolism reflect different brain physiological states, and a direct integrated study of brain perfusion and metabolism should be performed.
To date, this study is the first to investigate the prognostic value of CCD in FCD patients postoperatively; however, pioneering studies have explored its clinical significance in ischaemic patients. Sin et al  hypothesized that CCD was associated with poor motor recovery after 6 months in patients with haemorrhagic stroke assessed with the Fugl-Meyer Assessment (FMA) and the Korean version of the Modified Barthel Index (K-MBI) score, which is consistent with Small et al  who concluded that the occurrence of CCD had a close association with motor recovery using functional MRI. Sebök et al  included 25 cases with symptomatic unilateral cerebrovascular steno-occlusive disease and concluded that CCD + patients were in poorer clinical condition than CCD- patients after a 3-month follow-up: National Institutes of Health Stroke Scale (NIHSS) 2 vs 0, P = 0.02; modified Rankin Scale (mRS) 1 vs 0, P = 0.04. Other authors demonstrated that CCD has no prognostic value for stroke outcomes. Zhang et al  found no difference in the NIHSS score between CCD + and CCD- patients with acute ischaemic stroke, which is similar to the result obtained by Kunz et al . In summary, CCD is not only a concomitant symptom in diseases such as cerebral infarction and epilepsy but also an important indicator for functional recovery and prognosis. We need a more exact evaluation index in addition to the Engel class to explore the value of CCD in patients with epilepsy at baseline and during follow-ups.
The underlying pathophysiologic mechanism of CCD due to cerebral infarction is functional disruption of the cortico-ponto-cerebellar (CPC) pathways [26, 27]. Recently, Hong demonstrated that FCD lesions can influence whole-brain network integrity using structural equation modelling . CCD + patients showed more significant structural anomalies on MRI and a higher rate of the “severe” grade of hypometabolism in the frontal and temporal lobes and the whole brain than CCD- patients (P < 0.05), and parietal hypometabolism on PET may indicate a poor prognosis (P = 0.02), which are interesting findings of our study. We thought that these findings were closely related to the CPC pathways. Massaro  found CCD in patients with status epilepticus by MRI and attributed the finding to excessive neuronal transmission caused by prolonged excitatory synaptic activity from the supratentorial hemisphere to the contralateral cerebellum through the CPC pathway, resulting in increased energy metabolism and cerebral blood flow. Ictal 18F-FDG PET showed hypermetabolism, whereas hypometabolism is observed on interictal imaging. Sebök et al  found that CCD + patients showed more severely impaired supratentorial cerebrovascular reactivity than CCD- patients. Lindenberg et al  found that the integrity of motor fibre tracts was positively correlated with stroke recovery in 35 chronic stroke patients undergoing diffusion tensor imaging (DTI). In the next step, we will analyse differences in fibre tracts in CPC pathways between CCD + and CCD- epilepsy patients using integrated 18F-FDG PET/MR-DTI and determine the correlation between the grade of hypometabolism and the integrity of motor fibre tracts.
Some limitations exist in this retrospective research. First, the checkout offset cannot be avoided completely. Second, in this study, we performed only a semi-quantitative analysis to evaluate the severity of CCD and not a quantitative analysis. Despite these limitations, the population in this retrospective study was sufficiently large to investigate the predictors and clinical value of CCD and may provide a basis for further prospective research.