High gamma activity of 60–70 Hz in the area surrounding a cortical tuber in an infant with tuberous sclerosis
© Irahara et al.; licensee BioMed Central Ltd. 2012
Received: 20 January 2012
Accepted: 3 May 2012
Published: 3 May 2012
To detect the epileptogenic region causing epileptic spasms in an infant with tuberous sclerosis (TS).
We applied a multiple band frequency analysis to video electroencephalographic (EEG) recordings of the infant’s scalp. We also performed computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and magnetoencephalography (MEG) of the brain in order to ascertain the epileptic focus.
During the periodic spasms, we identified fast ictal activity with frequencies of 60–70 Hz in the right centroparietal region. This region was part of the area surrounding the largest cortical tuber that was identified on CT and MRI and was located in the right frontal lobe. An area of increased blood perfusion that was observed with SPECT and dipole sources that were determined with interictal MEG were also located in this area. In addition, ictal frequency oscillations (FOs) with high gamma activity were identified over the cortex surrounding the largest tuber. After a lesionectomy of this tuber, the periodic spasms disappeared, and no FOs were detected over this area.
Scalp EEG, which identified the ictal onset zone by detecting fast activity that was suggestive of FOs, was useful for detecting the epileptogenic region in an infant with TS.
Tuberous sclerosis (TS) is a neurocutaneous syndrome involving multiple organs. Because of abnormalities in migration, proliferation, and differentiation, characteristic hamartomas are found in the skin, retina, kidney, lung, heart, and brain. One of the most important complications of TS is epilepsy, which occurs in 80%–90% of cases . A common type of seizure is infantile spasms, which occur in approximately 30%–60% of patients with TS in the first month of life. Infantile spasms with localization-related epilepsies were first described as periodic spasms by Gobbi et al. ; they inferred that cortical mechanisms played a critical role in their pathophysiology. Recently, advances in digital electroencephalography (EEG) recording techniques have allowed recordings with high sampling frequencies. High-frequency oscillations (HFOs) with frequencies above 80 Hz that are observed on EEG are biomarkers of epileptogenesis, and they can be detected in focal cortical areas, implying that these are ictal onset zones [3, 4]. Furthermore, high gamma activity with frequencies of 50–80 Hz also appear in epileptogenic zones with ictal discharge . Therefore, not only HFOs, but also high gamma activity, may be useful for detecting epileptogenic zones. The detection of epileptogenic HFOs or high gamma activity, however, is typically performed using intracranial electrodes. Kobayashi et al. reported HFOs in scalp EEGs that were performed on patients with infantile spasms, and Yamazaki et al. observed fast activity in young children with hemimegalencephaly [6, 7]. Fast activity was detected just before the onset of spasms, and these findings suggested that the cortex played a major role in generating epileptic spasms [4, 5, 8]. Moreover, ictal high gamma activity occurred with slow waves that had spasms that were less than 1 Hz, although the origin of the slow wave was unknown . We describe the case of a 1-year-old girl with periodic spasms that were secondary to TS due to a TSC1 gene mutation. We performed a scalp EEG with a high-sampling frequency and analyzed the ictal fast activity on the scalp EEG by multiple band frequency analysis (MBFA).
Epileptic seizures in patients with TS are often refractory to regimens of many antiepileptic drugs. Patients with TS often have multiple tubers, and it is difficult to determine the epileptogenic tuber. Moreover, not only tubers, but also nontuberous regions of cortex could be sources of the epileptogenesis because some patients with TS have diffusely decreased gray matter volumes [10, 11] and diffuse cellular differentiation abnormalities . Recently, MEG, SPECT, and positron emission tomography studies have pointed to specific tubers as the source of seizures [13, 14], and surgical approaches involving lesionectomies of the target tubers have led to good control of the epilepsy [15, 16]. Although HFO analyses are useful for detecting the source of seizures, the detection of these sources has been thought to be difficult using scalp EEG because of attenuation or dissipation by the skull and scalp, a mixture of electromyogram (EMG) artifacts, or the small region where epileptic discharges occur. Thus, intracranial EEG has typically been performed in order to detect the source of the seizures. For neonates or infants, video monitoring using intracranial electrodes is rarely performed because of the risk of accidental removal or intracranial infection. However, for young children, fast-activity analyses of scalp EEGs have been recently applied [4, 7, 17], and it was found that high gamma activity was associated with ictal discharge in a patient with epileptic spasms . Using scalp EEG, we were able to detect and record repeated high gamma activity that had different spectra in this case compared to the EMG results that were reported previously . However, because we could not detect high gamma activity of the preceding seizures, they may have involved differences in the depth of their source or in the type of epilepsies.
This report has provided evidence from scalp EEG recordings that the cortex of the surrounding tuber may be potentially epileptogenic or symptomatogenic. As previously reported, high gamma activity appears in both epileptogenic  and symptomatogenic regions , and these findings are useful for surgical resections as well as for HFOs. During the spasms, high gamma activity was generated in the rolandic area . This activity appeared in the surrounding area of the right frontal tuber, and this area accorded with the location of interictal spike sources on MEG and increased blood perfusion on SPECT. These MEGSS might appear in a widespread area because they were detected during the interictal period. The electrodes that were placed above the tuber did not detect any high gamma activity, and SPECT showed decreased blood perfusion. Therefore, it was suggested that the tuber itself had no epileptic or symptomatogenic activity. However, high gamma activity was not detected around the resected tuber after the lesionectomy, and new high gamma activity arose over the contralateral lobe. In TS, after a lesionectomy, another tuber often exhibits new epileptogenicity, and thus, a lesionectomy may break the normal inhibitory system of the local epileptogenic network . However, we thought we should eliminate the periodic spasms because her development had arrested after she manifested this type of seizure. Even if high gamma activity in the right hemisphere showed only symptomatogenic regions of spasms, resecting this region and disconnecting the epileptic network could contribute to a decrease in or elimination of the spasms and improve her development. The resection might change the epileptic network to generate new high gamma activity and lead to the occurrence of another type of brief tonic seizure. However, her development improved gradually and achieved the equivalence of that of a healthy six-month-old. The frequency of her seizures decreased substantially one year after the operation, and she has been seizure-free one year and seven months postoperatively.
This report provided the first evidence of an epileptogenic region in an infant with TS using MBFA on scalp EEG data. The evidence of epileptogenicity that was based on these data accorded with the MBFA of the scalp EEG was useful in detecting the epileptogenic region. Moreover, the analysis of the scalp EEG using an MBFA is useful for a precise evaluation of the epileptogenetic region and may be evidence that is useful for surgical resection. However, in our study, the grids of the scalp EEG did not have a resolution high enough to allow for an examination of the detailed seizure onset region. A device, such as a high-density EEG, is needed for a more precise analysis. In addition, we were not able to analyze the ictal delta waves because we used a low-pass filter.
In conclusion, scalp EEG, which can identify the ictal onset zone by detecting gamma activity, is useful for detecting the epileptogenic region in an infant with TS.
Written informed consent was obtained from the patient’s relatives for publication of this case report.
This study was supported in part by an Intramural Research Grant (21–5, 21–6 and 22–6; Clinical Research for Diagnostic and Therapeutic Innovations in Developmental Disorders) for Neurological and Psychiatric Disorders of NCNP.
We would like to thank Dr. Niida Yo (Department of Pediatrics, Kanazawa University Graduate School of Medical Science) for the genetic analysis of the patient with tuberous sclerosis.
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