Failure of ≥ 2 AEDs trials is a commonly faced problem in epilepsy practice which needs meticulous assessment of patients for proper management [17]. The current study showed nearly one-third of originally diagnosed DRE patients in the epilepsy clinic had NEEE due toimprecise initial diagnosis of functional seizures because of SSA and/or EEG misinterpretation as well as faulty diagnosis of frequent pseudo-seizures occurring in controlled epileptic patients relied on the previous organic epileptic nature of their illnesses. Any initial misdiagnosis was followed by focusing on reduction of the ictus frequency rather than reanalysis and revision of the non-organic disease with consecutive unnecessary increase of AEDs and pushing the patients to the corner of seizure intractability. The most common NEEE were PNES followed by syncope, REM sleep behavior disorder, paroxysmal vertigo, and migraine. These results are in accordance with that of Wilkins and colleagues [18] as well as Hanrahan and colleagues [19] who claimed diagnostic delay of NEEE to faulty baseline epilepsy diagnosis as well as difficulty in diagnosis of PNES in epileptic patients with successive multiple trials to reduce seizure frequencies by increasing the AEDs.
The study showed that female sex, high seizure frequencies, shorter disease duration, and multiple or ambiguous semiology as well as prominent depressive and anxiety symptoms are in favor of PNES. The current results were concordant with that of Korucuk and colleagues [20] as well as Labate and colleagues [21] who stated that distinguishing PNES from true epileptic ones may be difficult even to experienced observers which must be suspected in any epileptic case with recurrent paroxysmal behavioral abnormalities. They also stated that the evolution of epilepsy monitoring units or the ability to utilize simultaneous video and long-term EEG recordings may be a key to diagnosis. PNES could be classified to generalized motor seizures, akinetic seizures, seizures with subjective symptoms, and focal motor seizures.
The current results revealed that family history of epilepsy, history of febrile convulsions, single seizure semiology, presence of aura, automatism, and nocturnal seizures are in accord with true-DRE. These results are concordant with the studies of Hintz and colleagues [22] as well as Guevara-González and colleagues [23] who showed that febrile convulsions, single seizure type, and nocturnal attacks as important diagnostic hallmarks of true-DRE. The study also, showed that all cases of true-DRE had focal onset semiology. TLE was the commonest by FLE, OLE, and lastly insular lobe epilepsy. These results agreed with Hintz and colleagues [22] who found that the largest proportion of focal DRE was TLE followed by FLE.
Long-term video EEG monitoring is the gold-standard investigation for DRE diagnosis with high accuracy of syndromic epilepsy classification, interictal discharge localization, and differentiation of true-DRE from NEEE [24]. The current study showed that long-term EEG video record is a highly sensitive procedure for diagnosis of true-DRE and identification of the SOZ but must be interpreted in the context of SSA analysis due to the possible epileptiform abnormalities in few patients with PNES with consecutive inclusion in the zone of DRE. The study also showed that patients with PNES had high incidences of ictal events during EEG recording which was very helpful in recognition of their functional seizure properties by the absence of pre-ictal SOZ activities and lack of alteration in the background activities before and after the ictus. These results agreed with the works of Cox and colleagues [25] as well as Elwan and colleagues [12] who showed that a valuable proportion of PNES patients had interictal EEG abnormalities attributed to abnormal functional connectivity density in frontal lobe cortex, sensorimotor cortex, cingulate gyrus, insula, and occipital cortex which could be evaluated by functional connectivity density mapping.
The study showed that 3-T MRI followed the epilepsy imaging protocols succeeded to identify structural epileptiform abnormalities in a valuable proportion of true-DRE patients with non-lesional 1.5-T MRI, yet one-third of true-DRE patients still had normal 3-T MRI. The most common structural abnormalities included MTS and FCDs. These results are in harmony with that of Duncan colleagues [26] who stated that cortical developmental abnormalities and neuronal architectural malformations including are the most common structural MRI abnormalities in the context of true-DRE cases.
Regarding 18-FDG-PET scan, the study revealed its high sensitivity for EZL in true-DRE patients where it showed regional brain hypometabolism congruent with the SOZ in 87.5% of 3-T MRI non-lesional patients. These results are in harmony with that of Capraz and colleagues [27] as well as Desarnaud and colleagues [28] who identified that interictal 18-FDG-PET scan is the most sensitive procedure for localization of TLE as well as SOZ of extratemporal origin even for MRI-negative patients.
The multimodality patients’ approach in this work revealed that all included patients with true-DRE had focal-onset seizures with TLE localization was the commonest SOZ followed by FLE, multifocal EZL, OLE, and, lastly, insular lobe epilepsy. At the same time, some patients with FLE/PET scan hypometabolism had TLE-like semiology possibly due to rapid propagation of the epileptic activities from the orbital frontal surface to the temporal lobe. These results are concordant with that of Elwan and colleagues [12] who studied retrospectively concordance values of variable diagnostic tools in pre-surgical evaluation workup for patients with DRE and correlated these results with rate of seizure freedom after epilepsy surgery as an indicator of accurate EZL and concluded that SSA had a high lateralizing and localizing value especially when combined with interictal as well as ictal scalp EEG, MRI, and PET scan.
