Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings.

The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.

Abdominal auras in patients with mesial temporal sclerosis.

To better clarify abdominal auras and their clinical correlates, we enrolled 331 temporal lobe epilepsy patients who received surgical treatment. Detailed descriptions of their auras were obtained before surgery and reconfirmed during postoperative outpatient follow-ups. Pathology revealed mesial temporal sclerosis (MTS) in 256 patients (77.3%) and 75 non-MTS. Of 214 MTS patients with auras, 78 (36.4%) reported abdominal auras (vs. 30.4% in non-MTS, p=0.439): 42 with left-sided seizure onset, and 36 with right-sided seizure onset. Moreover, 49 of the 78 MTS patients had abdominal auras accompanied by rising sensations (vs. 2 of 14 in non-MTS group, p=0.004). The "rising air" was initially described to locate to the epigastric (47.8%) or periumbilical area (45.7%) and mostly reached the chest (40.4%) or remained in the abdominal region (27.1%). An epigastric location of "rising air" favored a left-sided seizure onset, and non-epigastric areas favored right-sided seizure onset (p=0.018). Finally, we found that abdominal auras with or without rising sensations did not predict postoperative seizure outcomes.

The duration of sustained convulsive seizures determines the pattern of hippocampal neurogenesis and the development of spontaneous epilepsy in rats.

The duration of sustained seizures (SS) plays a crucial role in the occurrence of spontaneous recurrent seizures (SRS) in experimental animals. We tested whether rats with varying durations of initial convulsive SS exhibited differential neurogenesis patterns in the hippocampal dentate gyrus that may be related to subsequent epileptogenesis. Sprague-Dawley rats with pilocarpine-induced convulsive SS were divided into short SS (30 min) and long SS (2 h) groups. Their behavior was monitored to identify convulsive SRS. From 1 to 28 days post-SS, cell proliferation was evaluated by 5'-bromo-2'-deoxyuridine (BrdU) labeling and immature neuroblasts in the dentate gyrus were identified by doublecortin immunohistochemistry. Convulsive SRS was detected in 8 out of the 9 long SS rats, but not in the 9 short SS rats. During day 1-3, proliferative cells were diffusely localized throughout the hippocampus in the long SS rats but were primarily confined within the subgranular zone in the short SS rats. Within the subgranular zone, a significant increase in the number of BrdU-positive cells was found at days 3 and 7 after the long SS and on day 1 after the short SS. Notably, abnormal dendritic outgrowth and hilar-ectopic localization of doublecortin-positive cells were present in the long SS rats. In conclusion, aberrant hippocampal neurogenesis following long SS may contribute to the development of SRS.

[Treatment guidelines for acute and preventive treatment of cluster headache].

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated both the acute and the preventive treatments for cluster headache now being used in Taiwan, based on the principles of evidence- based medicine. We assessed the quality of clinical trials and levels of evidence, and referred to other treatment guidelines proposed by other countries. Throughout several panel discussions, we merged opinions from the subcommittee members and proposed a consensus on the major roles, recommended levels, clinical efficacy, adverse events and cautions of clinical practice regarding acute and preventive treatments of cluster headache. The majority of Taiwanese patients have episodic cluster headaches, because chronic clusters are very rare. Cluster headache is characterized by severe and excruciating pain which develops within a short time and is associated with ipsilateral autonomic symptoms. Therefore, emergency treatment for a cluster headache attack is extremely important. Within the group of acute medications currently available in Taiwan, the subcommittee determined that high-flow oxygen inhalation has the best evidence of effectiveness, followed by intranasal triptans. Both are recommended as first-line medical treatments for acute attacks. Oral triptans were determined to be second-line medications. For transitional prophylaxis, oral corticosteroids are recommended as the first-line medication, and ergotamine as the second-line choice. As for maintenance prophylaxis, verapamil has the best evidence and is recommended as the first-line medication. Lithium, melatonin, valproic acid, topiramate and gabapentin are suggested as the second-line preventive medications. Surgical interventions, including occipital nerve stimulation, deep brain stimulation, radiofrequency block of the sphenopalatine ganglion, percutaneous radiofrequency rhizotomy and trigeminal nerve section, are invasive and their long-term efficacy and adverse events are still not clear in Taiwanese patients; therefore, they are not recommended currently by the subcommittee. The transitional and maintenance prophylactic medications can be used together to attain treatment efficacy. Once the maintenance prophylaxis achieves efficacy, the transitional prophylactic medications can be tapered gradually. We suggest the corticosteroids be used within two weeks, if possible. The duration of maintenance treatment depends on the individual patient's clinical condition, and the medications can be tapered off when the cluster period is over.

Reflex absence epilepsy induced by gait.

Reflex epilepsy is characterized by seizures that are precipitated by a specific identifiable factor. We describe here the case of a 21-year-old man with notable absence epilepsy since the age of 11 who experienced generalized convulsions 2 years after onset (in the absence of antiepileptic therapy) and reflex absence seizures triggered by walking 7-10 steps. To our knowledge, this case report is the first describing reflex absence epilepsy seizures induced by gait.

Treatment-seeking behavior of people with epilepsy in Taiwan: a preliminary study.

To understand the treatment-seeking behavior of people with epilepsy (PWE), 403 PWE were surveyed using structured face-to-face interviews. Nearly half (49.1%) of them had previously tried complementary and alternative medicine (CAM); traditional Chinese medicine (51.5%) and temple worship (48.0%) were the most frequently used forms of CAM. In the 155 patients with adult-onset epilepsy, seeking CAM was substantially more common among females (OR=2.11, 95% CI=1.05-4.24, P=0.036), patients with frequent seizures (OR=2.68, 95% CI=1.30-5.53, P=0.008), patients with less educated parents (OR=2.16, 95% CI=1.06-4.41, P=0.034), and patients with religious beliefs (OR=2.84, 95% CI=1.23-6.56, P=0.015). In the 248 patients with childhood-onset epilepsy, frequent seizures (OR=2.23, 95% CI=1.32-3.77, P=0.003) and lower level of parental education (OR=2.71, 95% CI=1.45-5.06, P=0.002) were significantly associated with CAM use. The patients who seek CAM before receiving conventional medical treatment decreased after implementation of the National Health Insurance (NHI) (34/188 before NHI vs 22/215 after NHI, P=0.023). This study showed that the prevalence of CAM use by PWE in Taiwan is high and that a convenient NHI program can affect treatment-seeking behavior.

An atypical case of Lennox-Gastaut syndrome not associated with mental retardation: a nosological issue.

The characteristic electroclinical features of Lennox-Gastaut syndrome (LGS) have been extensively reported, but the influence of the constellation of slow spike-and-wave (SSW) complexes with multiple seizure types (including atypical absence seizures [AAS] and tonic seizures [TS]) on patients with this syndrome is still unclear. We report the case of a 28-year-old woman who developed AAS and brief asymmetric TS at the age of 14 years. Her seizure disorder met diagnostic criteria for LGS (SSW on electroencephalogram and multiple seizure types), but there was no intellectual impairment and an interictal alpha EEG. Even 14 years after the onset of her epilepsy, she maintained fairly normal cognitive function, although she was bothered by frequent brief and subtle episodes of AAS and TS.

Electrocorticogram changes during corpus callosotomy for uncontrolled symptomatic generalized epilepsy.

We report a 19-year-old man who presented to our facility with medically intractable, symptomatic generalized epilepsy manifesting as generalized tonic-clonic seizures (GTCs). Before he underwent an anterior callosotomy (6 cm), these seizures, which he had experienced for 11 years, seemed to have a left-sided focal origin. Intraoperatively, no epileptiform discharges were found on the electrocorticogram (ECoG) performed prior to sectioning, but more than 10 left-sided seizures were recorded after sectioning. In the 10 years since surgery, the patient's seizures have remained generalized; however, the frequency and severity of the seizures have decreased. These findings indicate that the presence of electrocorticographic seizures, as measured by ECoG immediately following callosotomy, may not predict a poor surgical outcome, even though such a finding might be indicative of epileptogenicity in general.

Gamma knife radiosurgery for the treatment of recurrent seizures after incomplete anterior temporal lobectomy.

To evaluate the efficacy and safety of gamma knife radiosurgery (GKS) in treating temporal lobe epilepsy, GKS was performed in four adult patients with recurrent complex partial seizures who underwent incomplete anterior temporal lobectomy (ATL) but were reluctant to undergo a second resective surgery. A marginal dose of 24.5-25Gy, corresponding to 65-70% isodose curve, was delivered to the treatment target that included the residual amygdala and the head and anterior body of the hippocampus. None of the patients had severe acute side effects but three patients had radiation-induced MRI signal changes around the target volume 13, 20, and 24 months after GKS, respectively. All four patients had significant seizure reduction during the first 6-month period and clinical efficacy persisted throughout the 2-year follow-up period. All of the patients also had improved neuropsychological profiles, including memory function and quality-of-life, compared to their pre-GKS conditions. In conclusion, the safety and clinical efficacy of GKS make it a reasonable and suitable therapeutic alternative for patients with recurrent seizures after incomplete ATL. A higher marginal dose of >25Gy and wider coverage may be more clinically beneficial but warrant further investigation.

Corpus callosotomy in a patient of hemimegalencephaly and Lennox-Gastaut syndrome.

We report the case of a girl with hemimegalencephaly (HME) and Lennox-Gastaut syndrome (LGS) treated by callosotomy at 1 year of age. Over 10 years, her seizure frequency and severity decreased markedly. Hemispherectomy is the main surgical option for HME although HME appears to correlate with a less favorable seizure outcome. However, the clinical presentation of LGS and possible generalized cortical dysplasia, which is indicative of a secondarily generalized epilepsy, might predict a favorable surgical outcome of corpus callosotomy in patients of HME, as in our case.

Plastic phase-locking and magnetic mismatch response to auditory deviants in temporal lobe epilepsy.

The magnetic equivalent (MMNm) of mismatch negativity may reflect auditory discrimination and sensory memory. To study whether temporal lobe epilepsy (TLE) affects automatic central auditory-change processing, we recorded magnetoencephalographic (MEG) responses to standard and duration-deviant sounds in 12 TLE patients and 12 age-matched controls, and repeated MEG measurement in 8 patients 6-30 months following epilepsy surgery and in 6 controls 3-8 months after their first measurement. We compared the MMNm between patients and controls, and also evaluated intertrial phase coherences as indexed by phase-locking factors (PLF) using wavelet-based analyses. We observed longer MMNm latencies for patients than for controls. Dipole modeling and minimum-current estimates together showed bi-frontotemporal sources for MMNm. The phase locking across trials was dominant at the 4- to 14-Hz band, and the main difference in PLF between deviant- and standard-evoked responses occurred in the time frame of 150-250 ms after stimulus onset. Notably, in the 5 patients who became seizure free after removal of right temporal epileptic focus, the phase-locking phenomena resulting from deviant stimuli were enhanced, and even more distributed in the frontotemporal regions. We conclude that mesial TLE might affect auditory-change detection, and a successful surgery causes a possible plastic change in phase locking of deviant-evoked signals.

Isolated acute hearing loss as the presenting symptom of leptomeningeal carcinomatosis.

Leptomeningeal carcinomatosis is characterized by diffuse infiltration of the meninges by metastatic cancer. We report a rare case of leptomeningeal carcinomatosis with an initial presentation of isolated acute hearing loss. Progressive unsteady gait and multiple cranial nerve palsies ensued. Computed tomography of the chest with contrast revealed a 2 cm nodule over the right upper lung. Cytology of cerebrospinal fluid confirmed the diagnosis of adenocarcinoma. The patient was discharged after diagnosis. Isolated acute hearing loss is a rare initial presentation in leptomeningeal carcinomatosis, not necessarily with a known history of malignancy. A high index of suspicion is mandatory for accurate diagnosis.

A comparison of seizure outcome after callosotomy in patients with Lennox-Gastaut syndrome and a positive or negative history for West syndrome.

PURPOSE: This retrospective study was designed to clarify the role of West syndrome in post-callosotomy seizure outcome in patients with Lennox-Gastaut syndrome. METHODS: From September 1989 to May 1999, 74 patients diagnosed with Lennox-Gastaut syndrome received anterior corpus callosotomy at Taipei Veterans General Hospital, Taiwan. All patients were followed for more than 4 years after surgery. Among them, 21 (28.4%) patients had a history of West syndrome (Group A) whereas 53 (71.6%) patients did not have a history of West syndrome (Group B). Postoperative seizure outcome was compared for these two patient groups. RESULTS: A total of 16 (76.2%) patients in Group A (positive history) and 29 (54.7%) patients in group B (negative history) achieved significant improvement in seizures after surgery (e.g., seizure reduction of more than 50%). There was no statistical significance (p=0.088) in the difference in outcome between the two groups. CONCLUSIONS: A history of West syndrome does not appear to influence post-callosotomy seizure outcome in patients with Lennox-Gastaut syndrome.

Selective posterior cerebral artery amobarbital test in patients with temporal lobe epilepsy for surgical treatment.

PURPOSE: To evaluate whether the selective posterior cerebral artery amobarbital test (PCAAT) can predict postoperative memory function in patients with temporal lobe epilepsy (TLE) for surgical treatment and its clinical safety. METHODS: The database included adult patients with intractable TLE undergoing presurgical evaluation at Taipei Veterans General Hospital between 1995 and 2002. The PCAAT was carried out on patients who had failed conventional intracarotid amobarbital test (IAT) or had IAT results that evoked a concern of postoperative memory function decline. A battery of learning and memory testing was performed immediately before and after injection of amobarbital into the peduncular segment of the posterior cerebral artery (PCA) on the presumed hemisphere of epileptogenicity. Neuropsychological assessments were followed in surgically treated patients. RESULTS: A total of 16 patients completed PCAAT successfully and underwent anterior temporal lobectomy (ATL). Four patients failed PCAAT angiographic procedures due to technical difficulty in one patient, transient signs of vasospasm in two patients, and subarachnoid hemorrhage in one patient. Of the 12 patients who performed well in PCAAT learning and memory testing items by free recall or recognition, only 1 patient demonstrated postoperative memory decline in follow-up neuropsychological assessments. In contrast, two of the four patients with a deficit in PCAAT memory testing showed postoperative memory decline. Regarding subjective memory function (not necessarily associated with objective memory decline), patients not seizure-free after ATL were more likely to have memory complaints (in 3 out of 6 patients) than patients with seizure-free outcomes (in 1 out of 10 patients). CONCLUSIONS: The PCAAT memory test reliably predicts postoperative memory function in patients with TLE for surgical treatment. However, the inherent risks of PCAAT must be considered and it should be used judiciously.

Prognostic value of electrocorticography findings during callosotomy in children with Lennox-Gastaut syndrome.

OBJECTIVE: To analyze findings and acute changes in electrocorticograms (ECoGs) obtained during corpus callosotomy in order to identify any relationships with the postoperative outcome of seizure activity. METHODS: We retrospectively analyzed ECoGs obtained during anterior callosotomy (4-6 cm) in 48 patients with Lennox-Gastaut syndrome (32 boys and 16 girls, age 1-20 years, mean age 7.6 years) who underwent surgery between July 1993 and November 1996 to correlate recording findings with postoperative seizure activity. At the time of analysis, all patients had been followed postoperatively for more than 4 years. RESULTS: Of 48 patients, 31 (64.6%) had significant improvement in seizure control after surgery. In pre-excisional ECoGs, 38 (79.2%) of 48 patients had bisynchronous epileptiform discharges. Patients (23 of 33 patients, 69.7%) with significant blockage of bisynchronous discharges recorded during callosotomy achieved the best postoperative seizure outcomes, but the difference did not reach statistical significance (P>0.05). CONCLUSIONS: Based on our experience, changes in ECoG during callosotomy do not predict postoperative seizure outcome. Insignificant blockage of bisynchronous epileptiform discharges in ECoGs during callosotomy does not predict a worse prognosis than that associated with significant intraoperative blockage.

[Another seizure classification--Semiological Seizure Classification].

The International League Against Epilepsy (ILAE) introduced in 1981 a seizure classification based on clinical semiology, interictal EEG findings, and ictal EEG patterns. Such classification depends heavily on detailed electroclinical correlation. After 20 years' progress in epileptology, many clinicians have found it difficult to make a "definite" seizure diagnosis clinically without a series of electrophysiological examinations, particularly in the infants, and further advancement in epileptology has findings have made the previous classification inefficient. Lüders and colleagues have proposed a classification, Semiological Seizure Classification (SSC), based exclusively on ictal semiology, which was published in the official journal of ILAE-EPILEPSIA in 1998. The EEG, neuroimaging and other laboratory results should be analyzed separately and then integrated to define the epileptic syndromes. The seizure diagnosis is thus made through a "what-you-see-is-what-you-get" way. It has also provoked an extensive discussion about the necessity of this new classification. In this review, we present the original guideline, which has been used at The Cleveland Clinic Foundation for years, to introduce another method of epileptic seizure classification.

Lateralisation value of lower limb behaviors in complex partial seizures of temporal lobe origin: a video-EEG analysis.

PURPOSE: To determine the lateralising value of leg behaviors in complex partial seizures (CPS) of temporal lobe onset. METHODS: Videotapes of 123 seizures from 38 patients who were seizure-free after temporal lobectomy were reviewed. Ictal behaviors including head turning, limb automatisms, tonic/dystonic postures and the latent time for ictal behavior were analysed for their lateralising value. RESULTS: Contralateral versive head turning, ipsilateral arm automatisms, contralateral arm tonic/dystonic posturing, and contralateral arm clonic posturing were found to have high predictive value of lateralisation. As for the lower limbs, meaningful leg behaviors were recorded in 38 (31%) of 123 seizures, far less than behaviors of the upper limbs (79%). The predictive value from leg behaviors were similar to that from upper limbs. Among the leg behaviors, dystonic behaviors were always contralateral to the ictal side. Tonic behaviors were 94% contralateral to the ictal side. Dystonia and clonic movement were always contralateral to the ictal side. Automatisms were 86% ipsilateral to the ictal side. CONCLUSIONS: Although incidences were low, leg behaviors could provide useful lateralising value of the seizure foci. Clinicians as well as investigators should recognize the value of lower limbs behavior in studies of ictal semiology.

Magnetoencephalographic analysis of bilaterally synchronous discharges in benign rolandic epilepsy of childhood.

The purpose of this study was to examine the spatial and temporal relationship between bilateral foci of bilaterally synchronous discharges in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We simultaneously recorded interictal magnetoencephalographic (MEG) and electroencephalographic (EEG) signals in six children with BREC. Interictal spikes were classified into three groups: bilaterally synchronous discharges (BSDs), unilateral discharges on right side (UD-R), and unilateral discharges on left side (UD-L). We used equivalent current dipole (ECD) modelling to analyse the cortical sources of interictal spikes. Both BSDs and UDs were found in Patients 1-4, whereas only UDs were identified in Patients 5 and 6. The ECDs of interictal spikes were located in rolandic regions, 10-20mm anterior and lateral to hand somatosensory cortices. Multi-dipole analysis of BSDs showed two ECDs in homotopic motor areas of the hemispheres. During BSDs, the right-sided activation preceded the left-sided activation by 15-21 milliseconds in Patients 1 and 2. In Patients 3 and 4, the activation occurred 17-20 milliseconds earlier in the left than the right hemisphere. Within the same hemisphere, the sources of BSDs and UDs were located in similar areas. In conclusion, our results imply the cortical epileptogenicity in bilateral perirolandic areas in BREC. The sequential activation during BSDs in both hemispheres suggest the existence of synaptic connections, possibly via the corpus callosum, between bilateral irritative foci.

Medication education for patients with epilepsy in Taiwan.

The aim of this study is to evaluate the medication knowledge achieved by conventional verbal education and the influence of drug information leaflets in patients with epilepsy. Drug compliance and sources of information of the patients were also examined. Fifty-one adults in an epilepsy outpatient clinic participated this survey. These patients were asked to complete a questionnaire and to specify sources of drug information. Serum drug levels were checked and compared with the self-reported compliance. Then, drug information leaflets were given to patients. In the next follow-up visit, patients were asked to fill out the same questionnaire again. In the baseline assessment, 36 patients (70.6%) could accurately list their medications. However, half of patients were not knowledgeable about side effects and did not keep a seizure diary. After provision of drug leaflets, the epilepsy medication assessment score increased from 3.9 +/- 1.9 to 5.1 +/- 1.7 (P<0.001). In addition, patients reported being compliant most of the time and this matched drug levels. On average, each patient had 2.8 sources of information and 5 patients used Internet as a tool. Despite achieving good compliance, conventional verbal education did not sufficiently cover drug-related issues. Providing patients with written information apparently increase their medication knowledge and probably enhance seizure control.