Intracerebrally recorded high frequency oscillations: Simple visual assessment versus automated detection

Objective

We compared the possible contribution (in the detection of seizure onset zone – SOZ) of simple visual assessment of intracerebrally recorded high-frequency oscillations (HFO) with standard automated detection.

Methods

We analyzed stereo-EEG (SEEG) recordings from 20 patients with medically intractable partial seizures (10 temporal/10 extratemporal). Independently using simple visual assessment and automated detection of HFO, we identified the depth electrode contacts with maximum occurrences of ripples (R) and fast ripples (FR). The SOZ was determined by independent visual identification in standard SEEG recordings, and the congruence of results from visual versus automated HFO detection was compared.

Results

Automated detection of HFO correctly identified the SOZ in 14 (R)/10 (FR) out of 20 subjects; a simple visual assessment of SEEG recordings in the appropriate frequency ranges correctly identified the SOZ in 13 (R)/9 (FR) subjects.

Conclusions

Simple visual assessment of SEEG traces and standard automated detection of HFO seem to contribute comparably to the identification of the SOZ in patients with focal epilepsies. When using macroelectrodes in neocortical extratemporal epilepsies, the SOZ might be better determined by the ripple range.

Significance

Standard automated detection of HFO enables the evaluation of HFO characteristics in whole data. This detection allows general purpose and objective evaluation, without any bias from the neurophysiologist’s experiences and practice.     

Hippocampal high frequency oscillations in unilateral and bilateral mesial temporal lobe epilepsy

ObjectiveThe main aim of this study was to investigate the potential differences in terms of interictal high frequency oscillations (HFOs) between both hippocampi in unilateral (U-MTLE) and bilateral mesial temporal lobe epilepsy (B-MTLE).MethodsSixteen patients with MTLE underwent bilateral hippocampal depth electrode implantation as part of epilepsy surgery evaluation. Interictal HFOs were detected automatically. The analyses entail comparisons of the rates and spatial distributions of ripples and fast ripples (FR) in hippocampi and amygdalae, with respect to the eventual finding of hippocampal sclerosis (HS).ResultsIn U-MTLE, higher ripple and FR rates were found in the hippocampi ipsilateral to the seizure onset than in the contralateral hippocampi. Non-epileptic hippocampi in U-MTLE were distinguished by significantly lower ripple rate than in the remaining analyzed hippocampi. There were not differences between the hippocampi in B-MTLE. In the hippocampi with proven HS, higher FR rates were observed in the ventral than in the dorsal parts.ConclusionsNon-epileptic hippocampi in U-MTLE demonstrated significantly lower ripple rates than those epileptic in U-MTLE and B-MTLE.SignificanceLow interictal HFO occurrence might be considered as a marker of the non-epileptic hippocampi in MTLE.     

Frequency-independent characteristics of high-frequency oscillations in epileptic and non-epileptic regions

Objective

The purpose of the presented study is to determine whether there are frequency-independent high-frequency oscillation (HFO) parameters which may differ in epileptic and non-epileptic regions.

Age-dependent seizure semiology in temporal lobe epilepsy

OBJECTIVE: To examine the effects of age on different aspects of temporal lobe seizure semiology. METHODS: We performed a video analysis of 605 archived seizures from 155 consecutive patients (age 10 months to 49 years) selected by seizure freedom after temporal lobectomy. Eighty patients had hippocampal sclerosis (HS). Beside semiological seizure classification, we assessed age dependency of several axes of seizure semiology: (1) aura, (2) number of different lateralizing signs, occurrence of ictal (3) emotional signs, (4) autonomic symptoms, (5) automatisms, and (6) secondary generalization as well as (7) the ratio of motor seizure components. RESULTS: From the 155 patients, 117 reported aura, 39 had ictal emotional signs, 51 had autonomic symptoms, 130 presented automatisms, while 18 patients showed secondary generalization at least once during their seizures. Altogether 369 (median: 2/patient) different lateralizing signs were recorded. Frequency of HS (p < 0.001), ictal automatisms (p < 0.001), secondary generalization (p = 0.014), number of different lateralizing signs (p < 0.001) increased while the ratio of motor seizure component (p = 0.007) decreased by age. Auras, emotional symptoms, and autonomic signs occurred independently of patients' ages. Hippocampal sclerosis adjusted linear models revealed that the frequency of automatisms and secondarily generalized seizures as well as the number of different lateralizing signs are HS-independent significant variables. CONCLUSION: Our findings support that brain maturation significantly influences the evolution of some important aspects (motor seizures, lateralizing signs) of temporal lobe seizure semiology. Conversely, other aspects (aura, emotional, and autonomic signs) are independent of the maturation process. This is the first report investigating age dependency of epileptic seizure semiology comparing all age groups.     

Remote memory in temporal lobe epilepsy

PURPOSE: The present study aims at characterizing remote memory in patients with temporal lobe epilepsy (TLE); it also considers the impact of its most important variables (lateralization of the lesion, duration of epilepsy, age at onset, and seizure frequency) on remote memory. METHODS: We examined the performance of 38 patients with unilateral TLE (19 right TLE and 19 left TLE) and 35 healthy subjects on six remote memory tasks. Memory for personal events was assessed by using the Autobiographical Memory Interview and the Modified Crovitz Test. Memory for public events was evaluated by means of photographs of famous faces and famous scenes, questions about famous events, and the Dead/Alive Test. RESULTS: Both right-TLE and left-TLE groups had impaired memory for autobiographic episodes and public events relative to normal subjects. In contrast, personal semantic memory was preserved. In addition, an effect of laterality was recorded, with right-TLE patients obtaining significantly better scores than left-TLE patients on every test. Duration of epilepsy, age at onset, and seizure frequency did not influence performance on remote memory measures. CONCLUSIONS: The comprehensive neuropsychological study of 38 TLE patients showed that this neurologic condition affects remote memory systems differently. We discuss the different factors that could account for this pattern of performance on the bases of both functional brain organization and memory theories.     

Thalamo-cortical network dysfunction in temporal lobe epilepsy

ObjectivesImaging and neurophysiological data shows that the cortical disfunction caused by focal epilepsy is not limited to the epileptic focus, thus raising the modern vision of focal epilepsy as a network disorder. The involvement of deep thalamo-cortical projections in temporal lobe epilepsy is a clear example. We aimed at demonstrating the interictal functional impairment of thalamo-cortical network in drug-naïve TLE patients through the study of high frequency oscillations of somatosensory evoked potentials (HF-SEP).MethodsTwelve healthy controls (HC; 8 females, 52.2 ± 17.3 years-old) and 12 drug-naïve TLE patients (8 females, 55.5 ± 21.5 years-old) underwent bilateral median HF-SEP, recorded by scalp electrodes. Cp3′-Fz and Cp4′-Fz traces were filtered (400–800 Hz) to evidence HF-SEP.ResultsHF-SEP duration in the affected hemisphere was significantly longer when compared to that of both the unaffected hemisphere and HC hemispheres. No significant inter-hemispheric differences were found in areas, powers and latencies of HF-SEP wavelets.ConclusionOur results demonstrate that TLE induces early interictal functional impairments of the thalamo-cortical network.SignificanceOur data strongly corroborates the vision of focal epilepsy as a network disorder and offers a new neurophysiological tool to test pharmacological, surgical and neuromodulatory therapies.     

Prognostic implication of contralateral secondary electrographic seizures in temporal lobe epilepsy

PURPOSE: Interhemispheric propagation of seizures in temporal lobe epilepsy is frequently noted during intracranial EEG monitoring. We hypothesized that a distinct secondary electrographic seizure (DSES) in the temporal lobe contralateral to primary seizure onset may be an unfavorable prognostic indicator. METHODS: We reviewed intracranial depth electrode EEG recordings, 1-year outcome, and medical records of 51 patients (M 29, F 22: age 15-64 years) who underwent anterior temporal lobectomy during 1988-96. We defined DSES as a seizure that spread to the contralateral temporal lobe and produced distinct contralateral EEG features. The distinct feature was focal involvement of one or two electrode contacts at onset, which starts and evolves independently from the ipsilateral temporal lobe. We considered DSES as the predominant seizure pattern when it occurred in more than one half of the patients' recorded seizures. RESULTS: Only nine of 19 (47%) patients with predominant DSES had a 1-year seizure-free outcome, whereas 27 of 32 (84%) patients without predominant DSES had a 1-year seizure-free outcome (p < 0.01). Bitemporal independent seizures were more common in patients with predominant DSES (9/19 versus 0/32; p < 0.001). CONCLUSION: Our results suggest that distinct contralateral secondary electrographic seizure is a predictor of unfavorable outcome and is also more likely to be associated with bitemporal seizures.     

Ictal head turning in frontal and temporal lobe epilepsy

Purpose: To quantitatively evaluate the difference of ictal head turning movements between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). Methods: We investigated 38 seizures of 31 patients with unilateral TLE and 22 seizures of 14 patients with unilateral FLE where head turning occurred in the seizure evolution. The head movements were defined as ipsilateral or contralateral in reference to the lateralization of the patient’s focal epilepsy syndrome. Head movements were quantified by either referencing the head position with manually placed markers or by automatic detection of infrared marked reference points. The time of onset, duration, and angular speed of the head movements were computed, and interindividual and intraindividual analyses were performed. Key Findings: All of the TLE seizures had both contralateral and ipsilateral head turning, whereas all FLE had contralateral head turning; only 6 of 22 seizures were associated with ipsilateral head turning. Ipsilateral head turning always preceded contralateral head turning in both TLE and FLE. The head turning occurred significantly sooner after clinical seizure onset in FLE than in TLE patients (ipsilateral 0.5 vs. 16.0 s, contralateral: 4.5 vs. 21.3 s; p < 0.001). Furthermore, the duration of head turning was shorter in FLE for contralateral head turning (4.1 s) than in TLE (contralateral 6.0 s, p < 0.01); the ipsilateral head turning in the two groups did not differ (3.0 vs. 2.9 s) in duration. The angular speed of head turning did not differ for ipsilateral and for contralateral head turning in FLE and TLE. Significance: Quantitative analysis of head turning demonstrates significant differences between patients with FLE and TLE. These differences likely represent differences in spread of epileptic activity. This information may be useful in the seizure evaluation of patients considered for resective epilepsy surgery.     

Very high frequency oscillations (over 1000 Hz) in human epilepsy

Objective

High frequency oscillations (HFO) of 100–500 Hz have been reported in epileptic human brain. However, the questions of how fast these oscillations can reach, and which frequency range is clinically important remain unanswered. We recorded interictal and ictal very high frequency oscillations (VHFO) of 1000–2500 Hz by subdural electrodes using 10 kHz sampling rate. We describe the characteristics of VHFO, and discuss their underlying mechanism and clinical significance.

Methods

Five patients with neocortical epilepsy were studied. All patients underwent intracranial EEG monitoring with subdural electrodes. EEG recording with sampling rate of 10 kHz was conducted. Histopathology revealed malformation of cortical development in all cases.

Results

In four of five patients, very high frequency activities of 1000–2500 Hz were detected in highly localized cortical regions (one to four electrodes in individual patient). We named these activities “very high frequency oscillations (VHFO)”. Interictally, VHFO appeared intermittently, and were interrupted by spikes. Sustained VHFO without spikes appeared around the start of seizures.

Conclusions

Both interictal and ictal VHFO can be recorded by subdural electrodes. Compared to HFO previously reported, VHFO have much higher frequency, more restricted distribution, smaller amplitude, and different timing of onset.

Significance

Recording of VHFO may be useful for identifying the epileptogenic zone.     

The localization and lateralization of memory deficits in children with temporal lobe epilepsy

PURPOSE: It is often reported that children with temporal lobe epilepsy (TLE) experience nonlateralized memory impairments. However, many of these studies have been exploratory and not based on memory theory. Further, differences between mesial and lateral subgroups have not been adequately examined. This study aimed to discern more specific patterns of memory impairment in children with TLE. METHODS: Forty-three children (5-16 years) with lesional TLE participated. Subjects were categorized in terms of lesion laterality (left, n = 21; right, n = 22) and intratemporal location (mesial, n = 31; lateral, n = 12). Verbal and nonverbal memory tasks were administered that reflected associative, allocentric and recognition paradigms. RESULTS: Facial recognition was poorer in right TLE (p = 0.03). There were no differences between left and right groups on any other memory task, even when comparisons were restricted to cases with mesial involvement. Irrespective of laterality, clear differences were observed between mesial and lateral lesion subgroups (arbitrary associative learning, p = 0.01; complex figure recall, p = 0.03). The lateral lesion subgroup displayed intact memory function relative to normative standards. CONCLUSIONS: Memory is more frequently impaired in children with mesial as opposed to lateral TLE. Tasks with an associative component discriminated between these subgroups, supporting an associative model of hippocampal function. With the exception of facial recognition, memory deficits were not lateralized. Therefore, the nature of memory impairment experienced by children with TLE cannot be extrapolated from adult models.     

Secondarily generalized seizures in temporal lobe epilepsy

Purpose: Secondarily generalized tonic–clonic seizure (SGTCS) may occur rarely in temporal lobe epilepsy (TLE), but SGTCS is the major risk factor for sudden death and for seizure‐related fatal injuries. Our aim was to investigate clinical factors associated with the occurrence of SGTCS in TLE by addressing two questions: (1) What clinical features differentiate patients with TLE who regularly had SGTCS from those who did not? (2) Is there an association of secondarily generalized seizures with preceding seizure elements and clinical data? Methods: We included 171 patients with TLE (mean age 34.4 ± 10) who participated in our presurgical evaluation program, which included continuous video–electroencephalography (EEG) and magnetic resonance imaging (MRI). Patients had a temporal lobectomy as a result of mesial or neocortical TLE. To reevaluate the archived seizures, we selected the consecutively recorded seizures of each patient. If the patient had more than three recorded seizures, then we reevaluated only the first three. Altogether video‐recorded seizures of 402 patients were reanalyzed. Key Findings: A positive association between the presence of hippocampal sclerosis on the MRI and SGTCS in the patient history was found, whereas ictal speech and pedal automatism showed a negative association with a SGTCS history. The age of patients showed a positive association, whereas patient’s reactivity before and during the seizure, oral/pedal automatisms, and vocalizations showed a negative association with secondary generalization of a focal‐onset seizure during video‐EEG monitoring. Significance: Clinical features associated with SGTCS may help clinicians during presurgical monitoring identify high‐risk patients for SGTCS. Our study may help in understanding the pathophysiology of secondary generalization.     

非病灶性药物难治性颞叶癫痫的致痫源定位与显微外科手术治疗

目的探讨非病灶性颞叶癫痫致痫源的定位并分析其显微外科手术治疗结果。方法收治的25例患者经临床表现、脑电图（EEG）／动态脑电图（VEEG）、MRI海马相、单光子发射断层扫描（SPECT）和正电子发射断层扫描（PET）检查诊断为非病灶性颞叶癫痫，均正规服用药物2年以上，但癫痫发作症状均未有效地控制。其中18例行标准前颞叶及海马杏仁核切除术，7例行选择性海马杏仁核切除术。结果随诊观察7～53个月，按照Engel术后疗效分级标准：Ⅰ级17例，Ⅱ级2例，Ⅲ级5例，Ⅳ级1例。结论致痫源的准确定位并采用显微外科技术可以提高手术疗效，减少并发症。     

Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy

Alterations in the balance of K‐Na‐2Cl cotransporter (NKCC1) and Na‐Cl cotransporter (KCC2) activity may cause depolarizing effect of γ‐aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. In the current pilot study we provide the first documented look at efficacy of bumetanide, a specific NKCC1 antagonist, on reduction of seizure frequency in adult patients with temporal lobe epilepsy. According to our results, seizure frequency was reduced considerably in these patients. Furthermore, epileptiform discharges decreased in two of our patients. If the efficacy of bumetanide is proven in large scale studies, it can be used as a supplemental therapy in temporal lobe epilepsy.     

MRI影像改变对颞叶癫痫术后疗效的影响

目的 研究颞叶癫痫(TLE)患者的MRI影像与病理结果 的相关性,分析不同MRI改变对术后疗效的影响.方法 回顾2005年1月至2008年12月在我科手术治疗且有效随访的121例TLE患者的临床资料,统计分析MRI影像改变与病理结果 的关系;根据MRI影像改变将患者分为内侧型TLE、有结构性改变的TLE和隐源性TLE,利用Engel分级将患者分为无发作组和发作组,比较不同类型TLE患者术后疗效的差异.结果 121例患者中MRI结果 阳性101例,病理结果 阳性107例,二者差异无统计学意义,具有良好的相关性.隐源性TLE患者的术后疗效较内侧型TLE和有结构性病变的TLE差,而后二者之间差异无统计学意义.结论 MRI检查对于TLE的确诊及预后判断具有重要意义.     

Mitochondrial involvement in temporal lobe epilepsy

Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca²⁺ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy

It has been hypothesized on the basis of animal models of epilepsy that abnormal neural activity in epilepsy may be related to reorganized neural circuits that facilitate epileptogenesis. Little evidence of this was available for human epilepsy. This paper provides the first evidence of such reorganization of a hippocampal seizure focus in human temporal lobe epilepsy (TLE). This reorganization involves the selective loss of somatostatin and neuropeptide Y immunoreactive interneurons, and axonal sprouting of other neuropeptide Y neurons and dynorphin-A immunoreactive granule cells. This set of changes is not exactly like those that are reported in animal models.     

Diffusion tensor analysis of temporal and extra-temporal lobe tracts in temporal lobe epilepsy

OBJECTIVE: To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties. METHODS: Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined. RESULTS: All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere. CONCLUSION: Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.