In our study we presented a group of patients with clinical suspicion of NCSE and EEG patterns showing non-epileptiform abnormalities. In our series, the use of QtSPECT concomitantly with the EEG allowed the diagnosis of NCSE in a majority of patients, with good sensibility and high specificity. Quantification allows a rapid interpretation and avoids the necessity of an interictal SPECT study.
Foremost, in the diagnosis of NCSE a clinical suspicion is needed. However, patients in NCSE can present with unspecific clinics, showing mild neurological symptoms like eye deviation or aphasia, which could mimic other diseases such as a stroke, or even go unnoticed. These symptoms may occur from onset or, in other occasions, appear after more evident seizure activity resolves, frequently delaying the diagnosis . Being this the case, the EEG is crucial in order to diagnose this condition; notwithstanding, it may not allow a definite diagnosis in some occasions, as there are patterns that do not allow for either confirm or discard NCSE . Especially in those cases where clinical suspicion is high, even non-specific EEG findings cannot reliably discard ongoing seizures [11,17]. In this report, we provide a description of a set of patients with high clinical suspicion of NCSE and an indefinite EEG pattern, in which the aid of neuroimaging is of substantial relevance for the diagnosis and management of these cases.
To date, there is increasing information about the utility of neuroimaging techniques as a diagnostic tool for NCSE, but its use in non-epileptiform patterns remains scarce. Most of the published studies are case series [11,17–23] and no direct comparison of EEG and neuroimaging studies accuracy was carried out in most of them. Some of these studies confirm the relation between increased perfusion imaging and the presence of confirmed NCSE with an ictal EEG pattern [18,19,22,23]. Those cases with non-epileptiform EEG patterns are unclear; small case-series studies reported how these non-epileptiform patterns can relate to focal hyperperfusion on neuroimaging, even in cases of irregular slowing [11,17,18,20,21].
The non-epileptiform patterns within the IIC remain a challenge. In our study we have found that lateralized patterns are more frequently associated to NCSE than generalized ones. Other studies have observed that LRDA has been associated with non-convulsive seizures , with a higher risk of seizures at higher frequencies . It has been found an association between LRDA and LPDs in up to 44% of the cases, suggesting that both LPDs and LRDA might have the same significance in relation with the presence of seizures . Less evidence is available for GRDA, which hasn’t been associated with seizures even at higher frequencies . On the other hand, patterns of irregular, lateralized, slowing have been described in patients with ongoing seizures , as we have also found. In fact, in a series of patients, these irregular slowing patterns on the scalp EEG have been proven to reflex the presence of deeper electrical seizures, detected by intracranial electrodes .
Injection of SPECT tracer has been approximated to take 30 seconds to reach the brain, where its uptake is dependent on a pattern of ictal perfusion remaining present for between 1 – 2 minutes, and around 70% of the ligand is taken . Consequently, SPECT imaging offers a good perfusion correlate of the EEG pattern at the time of the injection . Studies comparing SPECT with EEG-fMRI have also found a high correlation between perfusion measured by SPECT and real time fMRI-EEG findings . In this sense, SPECT is a good neuroimaging technique in order to relate the perfusion associated with different EEG patterns, and evaluate the presence of ongoing seizures, as it shows the real-time perfusion of the brain at the time of injection. In our series, patients with LRDA on the EEG at the time of injection showed hyperperfusion, together with other patients with more unspecific findings as irregular lateralized slowing (Table 2). This hyperperfusion was finally concordant with the diagnosis of NCSE, for all LRDA patterns and in some cases of more irregular lateralized slowing. Accordingly, we put forward the role of functional neuroimaging when these EEG patterns arose together with a high clinical suspicion.
However, some limitations of SPECT use should be considered. In acute neurological patients, the blood brain barrier is disturbed, and different patterns of perfusion can arise; the quantification of the results and the co-localization with the EEG could help to avoid overcalling unrelated perfusion changes. Different etiologies may produce hyperperfusion patterns, which may generate false positives; however, in our sample, no patient had a definite diagnosis of a pathology which could produce these findings (i.e. infectious encephalitis or high-grade glioma). On the other hand, compared to PET, SPECT does not measure metabolism, which could be more specific of ictal activity [17,20]. The main limitation of PET, however, is the prolonged uptake period of the tracer, which could yield results difficult to interpret , especially in patients with suspected NCSE, were admixed EEG patterns may be found. Also, as mentioned previously, the quantification of the SPECT allows a more robust interpretation of the hyperperfusion found, and helps eliminating sporous data.
Recently, a multimodal approach to evaluating the treatment options of patients in the IIC spectrum has been proposed . According to our data, QtSPECT can provide a useful and reliable multimodal approach to the acute patient, helping decision making. As mentioned previously, clinical suspicion is the basis of NCSE diagnosis, together with the EEG findings. Notwithstanding, as some limitations of the EEG, mainly the non-epileptiform patterns, could not reliable discard the diagnosis, selected patients could benefit of undergoing functional neuroimaging.
Our work has several limitations. In the first place, the limited number of patients; however, the pathology and EEG patterns reported is rare, and as the number of previous reports in the literature is low, we consider our series of significance. As the patients in our series had a high suspicion of NCSE, the groups are not equally balanced, which provides less information on the sensibility of the SPECT. Further data is needed in order to confirm our findings.