Epileptic network of hypothalamic hamartoma: An EEG-fMRI study
Introduction
Hypothalamic hamartoma (HH) is a rare developmental malformation that has provided important insight about epileptology (Berkovic et al., 1988, Mullatti et al., 2003, Striano et al., 2012). HH is characterized by gelastic seizures (GS) which occur in almost all patients. Such patients often develop other seizure types, i.e., partial and generalized seizures, and cognitive/behavioral problems including memory deficits and mental retardation. Previous studies showed that HH per se accounts for the generation of these seizures (Kahane et al., 2003, Kameyama et al., 2010, Kameyama et al., 2009, Kuzniecky, 2004, Munari et al., 1995, Striano et al., 2012, Wethe et al., 2013). Therefore, the unique spectrum of symptoms in HH has been regarded as the model of subcortical epilepsy and epileptic encephalopathy (Kameyama et al., 2010, Striano et al., 2012). However, it remains unknown how the epileptic activity propagates, and how cognitive/behavioral dysfunction develops. For example, the networks associated with GS remain elusive, although the mammillo-thalamo-cingulate tract from HH or the pathway from the HH to the brainstem and cerebellum has been postulated (Kahane et al., 2003, Kameyama et al., 2010). Therapeutically, stereotactic radiofrequency thermocoagulation (SRT) has become one of the most useful surgical interventions. SRT of the HH interface has yielded better outcomes for seizure freedom and fewer surgical complications than a direct approach (Kameyama et al., 2010, Kameyama et al., 2009). Subtraction ictal SPECT coregistered to MRI (SISCOM) has been used for locating the HH interface (Kameyama et al., 2010), however, it is time-consuming and the likelihood of detecting the HH interface individually is not high.
Here, we performed EEG with fMRI (EEG-fMRI) on eight patients with HH. EEG-fMRI can detect blood-oxygen-level dependent (BOLD) changes that are related to interictal discharges identified from scalp EEG (Lemieux et al., 2001, Warach et al., 1996). It was reported to be clinically useful for localizing the epileptic focus and investigating epileptic network even in the deep brain structures (Gotman and Pittau, 2011, Vulliemoz et al., 2010). In addition, it possibly predicts postsurgical outcome non-invasively although its clinical utility in comparison with other techniques, e.g. ictal SPECT, has been not determined (Chaudhary et al., 2013). With these in mind, we expected EEG-fMRI to clarify the common brain networks associated with subcortical epileptogenesis/encephalopathy in HH patients. Furthermore, we evaluated the clinical usefulness of EEG-fMRI in locating the HH interface in comparison with SISCOM (Kameyama et al., 2010). We thought EEG-fMRI would be an option for presurgical investigation, because it could provide us with the interictal epileptic network that could complement the findings of SISCOM in a relatively less time-consuming fashion.
Section snippets
Patients
Subjects were eight patients (pts.) with HH (age 1–27 years) (Table 1) who were examined at the Kyoto University Hospital from August 2011 to June 2013. Subjects included three patients who had received surgical intervention for HH in the past (pt. 2 as partial resection; pt. 6 as partial resection and SRT; pt. 7 as partial resection followed by infarction of the left hemisphere and gamma-knife surgery) with persisting seizures. Hamartomas were classified by the Delalande classification, which
Individual analysis
The areas that showed positive/negative BOLD activity (activation/deactivation) included cortical (e.g., neocortices including the insula and anterior cingulate cortices) and subcortical regions (e.g., the hypothalamus, thalamus, the caudate, brainstem, and cerebellum) to various degrees in all patients. In all six patients who showed cortical BOLD responses with early time-shift models (−8 – 0 s), the laterality of cortical activation was concordant with that of EEG spikes (Table 2). In 6/8
Strength of this study
We applied EEG-fMRI to patients with HH and revealed that its epileptic network comprised both neocortices and subcortical structures. Spike-related BOLD responses were observed interictally in all patients in various regions either with activation (positive BOLD) or deactivation (negative BOLD). In 6/8 patients, the hypothalamus with the HH interface or its adjacent area showed activation with a time-shift model before spike onset. Group analysis showed activation in the ipsilateral
Conclusion
In this study, we showed that EEG-fMRI in patients with HH detected brain areas possibly involved in epileptogenesis/encephalopathy, and that it had comparable sensitivity with SISCOM in detecting the HH interface. Future studies using EEG-fMRI would further expand our understanding about HH and its epileptogenesis, and corroborate the clinical usefulness of this technique.
Conflicts of interest
none.
Acknowledgments
RM has received support from Japan Ministry of Education, Culture, Sports, Science and Technology (MEXT): KAKENHI 26560465, 26282218, 23591273, 15H01664. AI has received support from MEXT: KAKENHI 15H05874, 26293209. MI has received support from MEXT: KAKENHI 15K09351. The remaining authors have no conflicts of interest. Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine is an endowment department, supported by grants from GlaxoSmithKline
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These authors are equally senior authors.