Naotaka Usui

The applications of time-frequency analyses to ictal magnetoencephalography in neocortical epilepsy

PURPOSEnIctal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propagation of ictal MEG activity in patients with neocortical epilepsy.nnnMETHODSnFour ictal MEG discharges in two patients with perirolandic epilepsy and one with frontal lobe epilepsy (FLE) were evaluated by time-frequency analyses using STFT. Prominent oscillation bands were collected manually and the magnitudes of those specific bands were superimposed on individual 3D-magnetic resonance images.nnnRESULTSnSTFT showed specific rhythmic activities from alpha to beta bands at the magnetological onset in all four ictal MEG records. Those activities were located at the vicinity of interictal spike sources, as estimated by the single dipole method (SDM), and two of the four ictal rhythmic activities promptly propagated to ipsilateral or bilateral cerebral cortices. The patients with FLE and perirolandic epilepsy underwent frontal lobectomy and resection of primary motor area, respectively including the origin of high-magnitude areas of a specific band indicated by STFT, and have been seizure free after the surgery.nnnCONCLUSIONSnSTFT for ictal MEG discharges readily demonstrated the ictal onset and propagation. These data were important for decisions on surgical procedure and extent of resection. Ictal MEG analyses using STFT could provide a powerful tool for noninvasive evaluation of ictal onset zone.

Developmental outcome after surgery in focal cortical dysplasia patients with early-onset epilepsy

The purpose of this study was to investigate the developmental outcome after surgery for early-onset epilepsy in patients with focal cortical dysplasia (FCD). Among 108 patients with histopathologically confirmed FCD operated between 1985 and 2008, we selected 17 patients with epilepsy onset up to 3 years of age. Development was evaluated by the developmental quotient or intelligence quotient (DQ-IQ) and mental age was measured by the Mother-Child Counseling baby test or the Tanaka-Binet scale of intelligence. Postsurgical development outcome was evaluated by the changes in DQ-IQ and mental age as well as rate of increase in mental age (RIMA) after surgery. RIMA was calculated as the increase in mental age per chronological year (months/year; normal average rate: 12 months/year). Age at epilepsy onset of 17 patients ranged from 15 days to 36 months (mean±SD, 11.0±10.0 months). Age at surgery ranged from 18 to 145 months (75.1±32.4 months). Evaluation just before surgery showed that 13 of 17 (76.4%) patients had DQ-IQ below 70. Ten patients (58.8%) were seizure-free throughout the postsurgical follow-up period. After surgery, DQ-IQ was maintained within 10 points of the presurgical level in 13 patients (76.4%), and increased by more than 10 points in one patient (5.9%). After surgery, RIMA in patients with Engels class I (7.5±3.8) was higher than patients with Engels class II-IV (2.6±3.4) (unpaired t-test with Welchs correction, t=2.99, df=15, p=0.0092). RIMA was particularly low in two patients with spasm. In four patients with presurgical DQ-IQ<70, seizure-free after surgery and without spasm, DQ-IQ did not increase but RIMA improved from 3.6±2.8 before surgery to 6.9±2.5 months/year after surgery. RIMA became better from 2 years after surgery. In four patients with presurgical DQ-IQ≥70 and no spasm, two showed the same or higher RIMA than normal average after surgery. In 58.8% of FCD patients with early onset epilepsy, epilepsy surgery effectively controlled seizures, and in 82.3% of patients, epilepsy surgery preserved or improved development. Residual seizures after surgery and lower DQ-IQ before surgery might be potential risk factors for poor development after surgery. In patients of Engels class I with lower presurgical DQ-IQ, catch-up increase in mental age was observed after two years following surgery.

Bidirectional electric communication between the inferior occipital gyrus and the amygdala during face processing

Faces contain multifaceted information that is important for human communication. Neuroimaging studies have revealed face‐specific activation in multiple brain regions, including the inferior occipital gyrus (IOG) and amygdala; it is often assumed that these regions constitute the neural network responsible for the processing of faces. However, it remains unknown whether and how these brain regions transmit information during face processing. This study investigated these questions by applying dynamic causal modeling of induced responses to human intracranial electroencephalography data recorded from the IOG and amygdala during the observation of faces, mosaics, and houses in upright and inverted orientations. Model comparisons assessing the experimental effects of upright faces versus upright houses and upright faces versus upright mosaics consistently indicated that the model having face‐specific bidirectional modulatory effects between the IOG and amygdala was the most probable. The experimental effect between upright versus inverted faces also favored the model with bidirectional modulatory effects between the IOG and amygdala. The spectral profiles of modulatory effects revealed both same‐frequency (e.g., gamma–gamma) and cross‐frequency (e.g., theta–gamma) couplings. These results suggest that the IOG and amygdala communicate rapidly with each other using various types of oscillations for the efficient processing of faces. Hum Brain Mapp 38:4511–4524, 2017.

Successful hemispherotomy in two refractory epilepsy patients with cerebral hemiatrophy and contralateral EEG abnormalities

We describe two cases of refractory epilepsy with cerebral hemiatrophy and contralateral electroencephalographic (EEG) abnormalities, in which hemispherotomy of the atrophic hemisphere effectively controlled seizures. Case 1 was a 5-year-1-month-old girl with refractory bilateral asymmetrical tonic posturing seizures predominantly in the right arm. Magnetic resonance imaging showed left porencephaly corresponding to a left middle cerebral artery infarction. Case 2 was a 3-year-8-month-old boy with refractory bilateral asymmetrical tonic posturing seizures predominantly in the right arm due to atrophy of the left cerebral hemisphere after septic meningitis. Both patients had right hemiparesis and was incapable of pinching by the right hand. Contralateral interictal and ictal EEG abnormalities were observed. Interictal 99mTc-ethyl cysteinate dimer (99mTc-ECD) single photon emission computed tomography (SPECT) showed hypoperfusion and ictal 99mTc-ECD-SPECT showed hyperperfusion within the left cerebral hemisphere. Left hemispherotomy was performed. Cases 1 and 2 remained seizure-free at the last follow-up 18u202fmonths and 15u202fmonths, respectively, after surgery, and contralateral interictal EEG abnormalities disappeared. In patients with cerebral hemiatrophy and contralateral EEG abnormalities, epilepsy surgery may be considered when the laterality of seizure semiology, functional imaging findings and motor deficits were concordant with the atrophic side. Ictal SPECT is effective to confirm the epileptogenic hemisphere.

Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia

OBJECTIVEnThe purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).nnnMETHODSn77 patients with histopathologically confirmed FCD were studied. The statistical relationship between cognition levels and clinical factors at presurgical evaluation was analyzed. Cognitive function was evaluated by development quotient or intelligence quotient (DQ-IQ).nnnRESULTSnAges at seizure onset were younger than 15u202fyears (meanu202f±u202fSD; 5.0u202f±u202f4.2u202fyears). Mean disease duration was 14.5u202f±u202f8.5u202fyears. Mean age at pre-surgical DQ-IQ evaluation was 34.8u202f±u202f10.7u202fyears. Mean DQ-IQ was 60.5u202f±u202f20.5, and 41 of 77 (53.2%) patients had mental retardation (DQ-IQu202f<u202f70). Younger seizure onset and seizure clustering were significantly associated with lower DQ-IQ (pu202f<u202f0.001). A multiple regression study identified higher seizure frequency pattern, a history of epileptic spasm and status epilepticus as aggravating factors of DQ-IQ decline (R2u202f=u202f0.63, pu202f<u202f0.001). On the other hand, the risk was decreased in patients with habitual focal aware seizure and transient seizure-free periods up to 6u202fmonths in the course of epilepsy. FCD location (FCD site, extent of radiological lesion and laterality) and histopathology of FCD did not affect DQ-IQ.nnnCONCLUSIONSnOur study suggests that seizure characteristics including higher seizure frequency pattern, a history of epileptic spasm, status epilepticus, seizure clustering and early onset of seizure are risk factors of cognitive impairment in FCD patients.

Influence of renal function on pharmacokinetics of antiepileptic drugs metabolized by CYP3A4 in a patient with renal impairment

Background: Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4. Methods: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment. Results: A patient with frontal lobe epilepsy and mild renal impairment [creatinine clearance (CCr): 67.7 mL/min] was taking phenytoin and 3 CYP3A4 substrates (topiramate, clobazam, and perampanel). With progression of renal impairment (CCr: 28.1 mL/min), the CD ratios of topiramate and clobazam increased by about 2-fold. The mean CD ratio of perampanel was 1740 ± 966 ng·mL−1·mg−1·kg−1 in the 17 patients with normal renal function using phenytoin. By contrast, the CD ratio of perampanel was markedly higher (range: 5327–9113 ng·mL−1·mg−1·kg−1) in the patient with renal impairment (CCr: <20 mL/min). Conclusions: These findings suggest that dose adjustment based on therapeutic drug monitoring is probably necessary when topiramate, clobazam, or perampanel is prescribed for patients with moderate-to-severe renal impairment.

Rapid gamma oscillations in the inferior occipital gyrus in response to eyes.

Eyes are an indispensable communication medium for human social interactions. Although previous neuroscientific evidence suggests the activation of the inferior occipital gyrus (IOG) during eye processing, the temporal profile of this activation remains unclear. To investigate this issue, we analyzed intracranial electroencephalograms of the IOG during the presentation of eyes and mosaics, in either averted or straight directions. Time–frequency statistical parametric mapping analyses revealed greater gamma-band activation in the right IOG beginning at 114u2009ms in response to eyes relative to mosaics, irrespective of their averted or straight direction. These results suggest that gamma oscillations in the right IOG are involved in the early stages of eye processing, such as eye detection.

Gamma Oscillations in the Temporal Pole in Response to Eyes.

The eyes of an individual act as an indispensable communication medium during human social interactions. Functional neuroimaging studies have revealed that several brain regions are activated in response to eyes and eye gaze direction changes. However, it remains unclear whether the temporal pole is one of these regions. Furthermore, if the temporal pole is activated by these stimuli, the timing and manner in which it is activated also remain unclear. To investigate these issues, we analyzed intracranial electroencephalographic data from the temporal pole that were obtained during the presentation of eyes and mosaics in averted or straight directions and their directional changes. Time–frequency statistical parametric mapping analyses revealed that the bilateral temporal poles exhibited greater gamma-band activation beginning at 215 ms in response to eyes compared with mosaics, irrespective of the direction. Additionally, the right temporal pole showed greater gamma-band activation beginning at 197 ms in response to directional changes of the eyes compared with mosaics. These results suggest that gamma-band oscillations in the temporal pole were involved in the processing of the presence of eyes and changes in eye gaze direction at a relatively late temporal stage compared with the posterior cortices.